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Sample records for proliferating breast cancer

  1. Sevoflurane suppresses proliferation by upregulating microRNA-203 in breast cancer cells.

    Science.gov (United States)

    Liu, Jiaying; Yang, Longqiu; Guo, Xia; Jin, Guangli; Wang, Qimin; Lv, Dongdong; Liu, Junli; Chen, Qiu; Song, Qiong; Li, Baolin

    2018-05-03

    Rapid proliferation is one of the critical characteristics of breast cancer. However, the underlying regulatory mechanism of breast cancer cell proliferation is largely unclear. The present study indicated that sevoflurane, one of inhalational anesthetics, could significantly suppress breast cancer cell proliferation by arresting cell cycle at G1 phase. Notably, the rescue experiment indicated that miR-203 was upregulated by sevoflurane and mediated the function of sevoflurane on suppressing the breast cancer cell proliferation. The present study indicated the function of the sevoflurane/miR-203 signaling pathway on regulating breast cancer cell proliferation. These results provide mechanistic insight into how the sevoflurane/miR-203 signaling pathway supresses proliferation of breast cancer cells, suggesting the sevoflurane/miR-203 pathway may be a potential target in the treatment of breast cancer.

  2. Ki67 and proliferation in breast cancer.

    Science.gov (United States)

    Pathmanathan, Nirmala; Balleine, Rosemary L

    2013-06-01

    New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. A major feature of this work has been to emphasise the importance of cancer cell proliferation as a key discriminative indicator of recurrence risk for oestrogen receptor positive breast cancer in particular. Mitotic count scoring, as a component of histopathological grade, has long formed part of a routine evaluation of breast cancer biology. However, there is an increasingly compelling case to include a specific proliferation score in breast cancer pathology reports based on expression of the cell cycle regulated protein Ki67. Immunohistochemical staining for Ki67 is a widely available and economical test with good tolerance of pre-analytical variations and staining conditions. However, there is currently no evidence based protocol established to derive a reliable and informative Ki67 score for routine clinical use. In this circumstance, pathologists must establish a standardised framework for scoring Ki67 and communicating results to a multidisciplinary team.

  3. Nifedipine promotes the proliferation and migration of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Dong-Qing Guo

    Full Text Available Nifedipine is widely used as a calcium channel blocker (CCB to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn't exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3. Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3-Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers.

  4. miR-613 inhibits proliferation and invasion of breast cancer cell via VEGFA

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    Wu, Junzhao; Yuan, Peng; Mao, Qixin [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Henan (China); Xie, Tian; Yang, Hanzhao [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China); Wang, Chengzheng, E-mail: wangchengzheng@126.com [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China)

    2016-09-09

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in breast cancer, has remained elusive. Here, we identified that miR-613 inhibits breast cancer cell proliferation by negatively regulates its target gene VEGFA. In breast cancer cell lines, CCK-8 proliferation assay indicated that the cell proliferation was inhibited by miR-613, while miR-613 inhibitor significantly promoted the cell proliferation. Transwell assay showed that miR-613 mimics significantly inhibited the migration and invasion of breast cancer cells, whereas miR-613 inhibitors significantly increased cell migration and invasion. Luciferase assays confirmed that miR-613 directly bound to the 3′ untranslated region of VEGFA, and western blotting showed that miR-613 suppressed the expression of VEGFA at the protein levels. This study indicated that miR-613 negatively regulates VEGFA and inhibits proliferation and invasion of breast cancer cell lines. Thus, miR-613 may represent a potential therapeutic molecule for breast cancer intervention.

  5. ERβ inhibits proliferation and invasion of breast cancer cells

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    Lazennec, Gwendal; Bresson, Damien; Lucas, Annick; Chauveau, Corine; Vignon, Françoise

    2001-01-01

    Recent studies indicate that the expression of ERβ in breast cancer is lower than in normal breast, suggesting that ERβ could play an important role in carcinogenesis. To investigate this hypothesis, we engineered estrogen-receptor negative MDA-MB-231 breast cancer cells to reintroduce either ERα or ERβ protein with an adenoviral vector. In these cells, ERβ (as ERα) expression was monitored using RT-PCR and Western blot. ERβ protein was localized in the nucleus (immunocytochemistry) and able to transactivate estrogen-responsive reporter constructs in the presence of estradiol. ERβ and ERα induced the expression of several endogenous genes such as pS2, TGFα or the cyclin kinase inhibitor p21, but in contrast to ERα, ERβ was unable to regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384 completely blocked ERα and ERβ estrogen-induced activities. ERβ inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas ERα inhibition of proliferation is hormone-dependent. Moreover, ERβ and ERα, decreased cell motility and invasion. Our data bring the first evidence that ERβ is an important modulator of proliferation and invasion of breast cancer cells and support the hypothesis that the loss of ERβ expression could be one of the events leading to the development of breast cancer. PMID:11517191

  6. GSE1 negative regulation by miR-489-5p promotes breast cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Chai, Peng; Tian, Jingzhong; Zhao, Deyin; Zhang, Hongyan; Cui, Jian; Ding, Keshuo; Liu, Bin

    2016-01-01

    Gse1 coiled-coil protein (GSE1), also known as KIAA0182, is a proline rich protein. However, the function of GSE1 is largely unknown. In this study, we reported that GSE1 is overexpression in breast cancer and silencing of GSE1 significantly suppressed breast cancer cells proliferation, migration and invasion. Furthermore, GSE1 was identified as a direct target of miR-489-5p, which is significantly reduced in breast cancer tissues. In addition, forced expression of miR-489-5p suppressed breast cancer cells proliferation, migration and invasion. Moreover, depletion of GSE1 by siRNAs significantly abrogated the enhanced proliferation, migration and invasion of breast cancer cells consequent to miR-489-5p depletion. Taken together, these findings suggest that GSE1 may function as a novel oncogene in breast cancer and it can be regulated by miR-489-5p. - Highlights: • GSE1 is overexpressed in breast cancer and increased GSE1 expression predicts poor prognosis in breast cancer patients. • Knockdown of GSE1 inhibits breast cancer cell proliferation, migration and invasion. • GSE1 is a direct target of miR-489-5p. • Forced expression of miR-489-5p inhibits breast cancer cell proliferation, migration and invasion.

  7. EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

    International Nuclear Information System (INIS)

    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline; Sun, Jianmin; Jögi, Annika; Neumann, Drorit; Rönnstrand, Lars; Påhlman, Sven

    2014-01-01

    Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα + ) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells

  8. EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

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    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Sun, Jianmin [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Jögi, Annika [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Neumann, Drorit [Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Rönnstrand, Lars [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Påhlman, Sven, E-mail: sven.pahlman@med.lu.se [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

    2014-02-28

    Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα{sup +}) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.

  9. PDGF-AB rich-trombocyte lysate supplementation from breast cancer patients increased the proliferation of breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Wiwi A. Kartolo

    2018-05-01

    Full Text Available Background: Thrombocytosis in breast cancer (BC patient was thought to play a role in the invasiveness of breast cancer stem cells (BCSCs. Modification of tumor microenvironment was proposed to increase the efficacy of anticancer therapy. This study was aimed to analyze the effect of platelet lysate (PL as well as its PDGF-AB content as a tumor microenvironment on (CD24-/CD44+ BCSC proliferation.Methods: This was an experimental study that treated culture of BCSCs with PL from breast cancer (BC patients or healthy donors. Venous blood from all subjects were subjected to prior hematology test and then processed to obtain platelet rich plasma  (PRP. Platelet counts in PRP were determined. PRP was processed to obtain PL. PDGF-AB contents in PL were measured. PL at concentrations of 0.01% (v/v was supplemented into DMEM-F12 medium and used for culturing BCSCs (CD24-/CD44+ cells. After 48 hours, total cell count, population doubling time (PDT, and cell viability were calculated and their correlation with platelet count and PDGF-AB levels were analyzed.Results: BC patients (n=5 had higher platelet counts and PDGF-AB levels in PL compared to healthy donors (n=15, (p=0.02. PL from BC patients could stimulate the proliferation of BCSCs higher than healthy donors (p<0.001 and showed lower PDT value (p=0.001. Cell proliferation and PDT showed strong correlation with PDGF-AB level. This observation suggests that PDGF-AB has a role on BCSCs proliferation. PL showed no effect on BCSCs viability.Conclusion: Breast cancer patient platelet lysate stimulated BCSC proliferation.

  10. Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

    International Nuclear Information System (INIS)

    Zhang, Yu; Cheng, Jung-Chien; Huang, He-Feng; Leung, Peter C.K.

    2013-01-01

    Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells

  11. Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

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    Zhang, Yu [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Cheng, Jung-Chien [Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Huang, He-Feng, E-mail: huanghefg@hotmail.com [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Leung, Peter C.K., E-mail: peter.leung@ubc.ca [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada)

    2013-11-01

    Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.

  12. Knockdown of Ran GTPase expression inhibits the proliferation and migration of breast cancer cells.

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    Sheng, Chenyi; Qiu, Jian; Wang, Yingying; He, Zhixian; Wang, Hua; Wang, Qingqing; Huang, Yeqing; Zhu, Lianxin; Shi, Feng; Chen, Yingying; Xiong, Shiyao; Xu, Zhen; Ni, Qichao

    2018-05-03

    Breast cancer is the second leading cause of cancer‑associated mortality in women worldwide. Strong evidence has suggested that Ran, which is a small GTP binding protein involved in the transport of RNA and protein across the nucleus, may be a key cellular protein involved in the metastatic progression of cancer. The present study investigated Ran gene expression in breast cancer tissue samples obtained from 140 patients who had undergone surgical resection for breast cancer. Western blot analysis of Ran in breast cancer tissues and paired adjacent normal tissues showed that expression of Ran was significantly increased in breast cancer tissues. Immunohistochemistry analyses conducted on formalin‑fixed paraffin‑embedded breast cancer tissue sections revealed that Ran expression was associated with tumor histological grade, nerve invasion and metastasis, vascular metastasis and Ki‑67 expression (a marker of cell proliferation). Kaplan‑Meier survival analysis showed that increased Ran expression in patients with breast cancer was positively associated with a poor survival prognosis. Furthermore, in vitro experiments demonstrated that highly migratory MDA‑MB‑231 cancer cells treated with Ran‑si‑RNA (si‑Ran), which knocked down expression of Ran, exhibited decreased motility in trans‑well migration and wound healing assays. Cell cycle analysis of Ran knocked down MDA‑MB‑231 cells implicated Ran in cell cycle arrest and the inhibition of proliferation. Furthermore, a starvation and re‑feeding (CCK‑8) assay was performed, which indicated that Ran regulated breast cancer cell proliferation. Taken together, the results provide strong in vitro evidence of the involvement of Ran in the progression of breast cancer and suggest that it could have high potential as a therapeutic target and/or marker of disease.

  13. [Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation].

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    Shi, Jianhong; Lü, Xinrui; Wang, Bing; Daudan, Lin; Yanan, Wang; Yuhui, Bu; Zhenfeng, Ma

    2014-09-30

    To explore the roles of Y box-binding protein 1 (YB-1) in breast cancer cell proliferation. Twenty cases of surgical removal of breast cancer tissue (diagnosed with invasive ductal carcinoma, stage II, by postoperative paraffin pathology) and normal breast tissues adjacent to carcinoma were collected during June 2013 to August 2013.Quantitative real-time PCR (qRT-PCR) was performed to detect the YB1 mRNA levels. Cultured mammary epithelial cells (HBL-100) and breast cancer cells (MCF7, MDA-MB-231 & SK-BR-3 cells) were harvested and qRT-PCR was performed to detect the YB1 mRNA levels.SK-BR-3 cells were stimulated with various concentrations of PDGF-BB and YB1 expression levels were detected by qRT-PCR. Down-regulation or over-expression of YB1 by si-YB1 or Ad-GFP-YB1 was detected in SK-BR-3 cells. And MTS cell proliferation assay kit was used to detect cell proliferation. YB1 mRNA levels were significantly higher in breast cancer tissues and MDA-MB-231 and SK-BR-3 breast cancer cell lines than that in adjacent normal breast tissues and HBL-100 mammary epithelial cells respectively (P BR-3 cells in a dose-dependent manner. A down-regulation of endogenous YB1 decreases and an over-expression of exogenous YB1 promotes the proliferation activity in SK-BR-3 cells.

  14. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

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    Hua, Wei [Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Yang, An-Gang [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Rui, E-mail: ruizhang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Fan, Jing, E-mail: jingfan@fmmu.edu.cn [Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Bian, Ka, E-mail: kakamax85@hotmail.com [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Department of Otolaryngology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-08-07

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells.

  15. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    International Nuclear Information System (INIS)

    Hua, Wei; Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing; Yang, An-Gang; Zhang, Rui; Fan, Jing; Bian, Ka

    2015-01-01

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells

  16. Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway

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    Ahn, Hee-Jin [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of); Kim, Gwangil [Department of Pathology, CHA Bundang Medical Center, CHA University, Seoul (Korea, Republic of); Park, Kyung-Soon, E-mail: kspark@cha.ac.kr [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of)

    2013-08-09

    Highlights: •Ell3 enhances proliferation and drug resistance of breast cancer cell lines. •Ell3 is related to the cancer stem cell characteristics of breast cancer cell lines. •Ell3 enhances oncogenicity of breast cancer through the ERK1/2 signaling pathway. -- Abstract: Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven−nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK−extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway.

  17. Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway

    International Nuclear Information System (INIS)

    Ahn, Hee-Jin; Kim, Gwangil; Park, Kyung-Soon

    2013-01-01

    Highlights: •Ell3 enhances proliferation and drug resistance of breast cancer cell lines. •Ell3 is related to the cancer stem cell characteristics of breast cancer cell lines. •Ell3 enhances oncogenicity of breast cancer through the ERK1/2 signaling pathway. -- Abstract: Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven−nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK−extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway

  18. Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

    International Nuclear Information System (INIS)

    Guo, Hongsheng; Wu, Fenping; Wang, Yan; Yan, Chong; Su, Wenmei

    2014-01-01

    Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found that Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management

  19. Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

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    Guo, Hongsheng [Department of Histology and Embryology, Guangdong Medical College, Dongguan 523808, Guangdong (China); Wu, Fenping [The 7th People’s Hospital of Chengdu, Chengdu 610041, Sichuan (China); Wang, Yan [The Second School of Clinical Medicine, Guangdong Medical College, Dongguan 523808, Guangdong (China); Yan, Chong [School of Pharmacy, Guangdong Medical College, Dongguan 523808, Guangdong (China); Su, Wenmei, E-mail: wenmeisutg@126.com [Oncology of Affiliated Hospital Guangdong Medical College, Zhanjiang 524000, Guangdong (China)

    2014-08-08

    Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found that Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management.

  20. Correlation of contrast-enhanced ultrasound parameters with oncogene expression and cell proliferation activity in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ce Zhang

    2017-01-01

    Objective: To study the correlation of contrast-enhanced ultrasound parameters with oncogene expression and cell proliferation activity in breast cancer. Methods: Breast cancer lesions and benign breast lesions surgically removed in Zigong Third People's Hospital between May 2014 and February 2017 were selected, contrast-enhanced ultrasound was done before operation to draw the time-intensity curve and calculate the area under the curve (AUC), and the expression of proliferation molecules and tumor suppressor genes were detected after operation. Results:The contrast-enhanced ultrasound parameter AUC of the breast cancer lesion was greatly higher than that of the benign breast lesion; ECT2, ZKSCAN3, USP39 and EphA2 mRNA expression in breast cancer lesions were obviously higher than those in benign breast lesions whereas HPK1, TCEAL17, CCN5, ATG2B and ATG4D mRNA expression were greatly lower than those in benign breast lesions; ECT2, ZKSCAN3, USP39 and EphA2 mRNA expression in breast cancer lesions with high AUC were greatly higher than those in breast cancer lesions with low AUC whereas HPK1, TCEAL17, CCN5, ATG2B and ATG4D mRNA expression were greatly lower than those in breast cancer lesions with low AUC. Conclusion: The contrast-enhanced ultrasound parameter AUC of breast cancer lesion significantly increases and is closely related to the higher expression of pro-proliferation molecules and the lower expression of tumor suppressor genes.

  1. Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

    International Nuclear Information System (INIS)

    Androic, Ilija; Krämer, Andrea; Yan, Ruilan; Rödel, Franz; Gätje, Regine; Kaufmann, Manfred; Strebhardt, Klaus; Yuan, Juping

    2008-01-01

    Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy

  2. Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

    Directory of Open Access Journals (Sweden)

    Strebhardt Klaus

    2008-12-01

    Full Text Available Abstract Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1, is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.

  3. MiR-132 prohibits proliferation, invasion, migration, and metastasis in breast cancer by targeting HN1

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhan-Guo, E-mail: zhang_zhanguo@hotmail.com; Chen, Wei-Xun, E-mail: chenweixunclark@163.com; Wu, Yan-Hui, E-mail: wuyanhui84@126.com; Liang, Hui-Fang, E-mail: lianghuifang1997@126.com; Zhang, Bi-Xiang, E-mail: bixiangzhang@163.com

    2014-11-07

    Highlights: • MiR-132 is down-regulated in breast cancer tissues and cell lines. • MiR-132 directly regulates HN1 by binding its 3′ UTR. • MiR-132 shows regulatory role in proliferation, invasion, migration and metastasis. • HN1 is involved in miR-132-mediated cell behavior. • Aberrant HN1 is associated with worse overall survival of breast cancer patients. - Abstract: Accumulating evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. This study aims to investigate the role and the underlying mechanism of miR-132 in breast cancer. Here, we report that miR-132 is significantly down-regulated in breast cancer tissues and cancer cell lines. Additional study identifies HN1 as a novel direct target of miR-132. MiR-132 down-regulates HN1 expression by binding to the 3′ UTR of HN1 transcript, thereby, suppressing multiple oncogenic traits such as cancer cell proliferation, invasion, migration and metastasis in vivo and in vitro. Overexpression of HN1 restores miR-132-suppressed malignancy. Importantly, higher HN1 expression is significantly associated with worse overall survival of breast cancer patients. Taken together, our data demonstrate a critical role of miR-132 in prohibiting cell proliferation, invasion, migration and metastasis in breast cancer through direct suppression of HN1, supporting the potential utility of miR-132 as a novel therapeutic strategy against breast cancer.

  4. Expression of Caspase-1 in breast cancer tissues and its effects on cell proliferation, apoptosis and invasion.

    Science.gov (United States)

    Sun, Yanxia; Guo, Yingzhen

    2018-05-01

    The present study aimed to detect the expression of Caspase-1 in the tumor tissues and tumor-adjacent tissues of patients with breast cancer, and to investigate the effects of Caspase-1 on the proliferation, apoptosis and invasion of breast cancer cells. Reverse transcription-quantitative polymerase chain reaction was used to detect Caspase-1 mRNA expression in breast cancer tissues and tumor-adjacent tissues from patients. Additionally, the human breast cancer MDA-MB-231 cell line was treated with the Caspase-1 small molecule inhibitor Ac-YVAD-CMK, following which the changes to Caspase-1 protein expression were detected via western blotting. The MTT method detected the changes to cell proliferation, flow cytometry detected the rate of apoptosis, and a Transwell assay was employed to assess invasion. Caspase-1 mRNA expression was significantly decreased in the breast cancer tissues of patients, compared with in the tumor-adjacent tissues, a difference that was statistically significant (P<0.05). Treatment with the Ac-YVAD-CMK markedly decreased the protein expression of Caspase-1 in MDA-MB-231 cells, and the difference was statistically significant (P<0.05). Following this treatment of Ac-YVAD-CMK cells, the proliferation and invasion abilities markedly increased, while the apoptotic levels significantly decreased (P<0.05). In conclusion, the expression of Caspase-1 is low in breast cancer tissues, which may promote the proliferation and invasion of breast cancer cells and could be closely associated with the occurrence and development of breast cancer.

  5. Taraxacum officinale dandelion extract efficiently inhibited the breast cancer stem cell proliferation

    OpenAIRE

    Ngu Van Trinh; Nghi Doan-Phuong Dang; Diem Hong Tran; Phuc Van Pham

    2016-01-01

    Background: Breast cancer stem cells (BCSCs) play an important role in breast cancer initiation, metastasis, recurrence, and drug resistance. Therefore, targeting BCSCs is an essential strategy to suppress cancer growth. This study aimed to evaluate the effects of dandelion Taraxacum officinale extracts on BCSC proliferation in vitro in 2D and 3D cell culture platforms. Materials and Methods: The BCSCs were maintained under standard conditions, verified for expression of CD44 and CD24 surface...

  6. miR-30a suppresses breast cancer cell proliferation and migration by targeting Eya2

    International Nuclear Information System (INIS)

    Fu, Jing; Xu, Xiaojie; Kang, Lei; Zhou, Liying; Wang, Shibin; Lu, Juming; Cheng, Long; Fan, Zhongyi; Yuan, Bin; Tian, Peirong; Zheng, Xiaofei; Yu, Chengze; Ye, Qinong; Lv, Zhaohui

    2014-01-01

    Highlights: • miR-30a represses Eya2 expression by binding to the 3′-untranslated region of Eya2. • The miR-30a/EYA2 axis regulates breast cancer cell proliferation and migration. • The miR-30a/EYA2 axis modulates G1/S cell cycle progression. • The miR-30a/EYA2 axis is dysregulated in breast cancer patients. - Abstract: Eye absent (Eya) proteins are involved in cell fate determination in a broad spectrum of cells and tissues. Aberrant expression of Eya2 has been documented in a variety of cancers and correlates with clinical outcome. However, whether microRNAs (miRNAs) can regulate Eya2 expression remains unknown. Here, we show that miR-30a represses Eya2 expression by binding to the 3′-untranslated region of Eya2. Overexpression of Eya2 in miR-30a-transfected breast cancer cells effectively rescued the inhibition of cell proliferation and migration caused by miR-30a. Knockdown of Eya2 by small-interfering RNA (siRNA) in breast cancer cells mimicked the effect induced by miR-30a and abolished the ability of miR-30a to regulate breast cancer cell proliferation and migration. The miR-30a/Eya2 axis could regulate G1/S cell cycle progression, accompanied by the modulation of expression of cell cycle-related proteins, including cyclin A, cyclin D1, cyclin E, and c-Myc. Moreover, miR-30a expression was downregulated in breast cancer patients, and negatively correlated with Eya2, which was upregulated in breast cancer patients. These data suggest that the miR-30a/Eya2 axis may play an important role in breast cancer development and progression and that miR-30a activation or Eya2 inhibition may be a useful strategy for cancer treatment

  7. Nuclear location of tumor suppressor protein maspin inhibits proliferation of breast cancer cells without affecting proliferation of normal epithelial cells

    International Nuclear Information System (INIS)

    Machowska, Magdalena; Wachowicz, Katarzyna; Sopel, Mirosław; Rzepecki, Ryszard

    2014-01-01

    Maspin, which is classified as a tumor suppressor protein, is downregulated in many types of cancer. Several studies have suggested potential anti-proliferative activity of maspin as well as sensitizing activity of maspin for therapeutic cytotoxic agents in breast cancer tissue culture and animal models. All of the experimental data gathered so far have been based on studies with maspin localized cytoplasmically, while maspin in breast cancer tumor cells may be located in the cytoplasm, nucleus or both. In this study, the effect of maspin cytoplasmic and nuclear location and expression level on breast cancer proliferation and patient survival was studied. Tissue sections from 166 patients with invasive ductal breast cancer were stained by immunohistochemistry for maspin and Ki-67 protein. The localization and expression level of maspin were correlated with estimated patient overall survival and percent of Ki-67-positive cells. In further studies, we created constructs for transient transfection of maspin into breast cancer cells with targeted cytoplasmic and nuclear location. We analyzed the effect of maspin location in normal epithelial cell line MCF10A and three breast cancer cell lines - MCF-7, MDA-MB-231 and SKBR-3 - by immunofluorescence and proliferation assay. We observed a strong positive correlation between moderate and high nuclear maspin level and survival of patients. Moreover, a statistically significant negative relationship was observed between nuclear maspin and Ki-67 expression in patients with invasive ductal breast cancer. Spearman’s correlation analysis showed a negative correlation between level of maspin localized in nucleus and percentage of Ki-67 positive cells. No such differences were observed in cells with cytoplasmic maspin. We found a strong correlation between nuclear maspin and loss of Ki-67 protein in breast cancer cell lines, while there was no effect in normal epithelial cells from breast. The anti-proliferative effect of nuclear

  8. Nuclear location of tumor suppressor protein maspin inhibits proliferation of breast cancer cells without affecting proliferation of normal epithelial cells

    Science.gov (United States)

    2014-01-01

    Background Maspin, which is classified as a tumor suppressor protein, is downregulated in many types of cancer. Several studies have suggested potential anti-proliferative activity of maspin as well as sensitizing activity of maspin for therapeutic cytotoxic agents in breast cancer tissue culture and animal models. All of the experimental data gathered so far have been based on studies with maspin localized cytoplasmically, while maspin in breast cancer tumor cells may be located in the cytoplasm, nucleus or both. In this study, the effect of maspin cytoplasmic and nuclear location and expression level on breast cancer proliferation and patient survival was studied. Methods Tissue sections from 166 patients with invasive ductal breast cancer were stained by immunohistochemistry for maspin and Ki-67 protein. The localization and expression level of maspin were correlated with estimated patient overall survival and percent of Ki-67-positive cells. In further studies, we created constructs for transient transfection of maspin into breast cancer cells with targeted cytoplasmic and nuclear location. We analyzed the effect of maspin location in normal epithelial cell line MCF10A and three breast cancer cell lines - MCF-7, MDA-MB-231 and SKBR-3 - by immunofluorescence and proliferation assay. Results We observed a strong positive correlation between moderate and high nuclear maspin level and survival of patients. Moreover, a statistically significant negative relationship was observed between nuclear maspin and Ki-67 expression in patients with invasive ductal breast cancer. Spearman’s correlation analysis showed a negative correlation between level of maspin localized in nucleus and percentage of Ki-67 positive cells. No such differences were observed in cells with cytoplasmic maspin. We found a strong correlation between nuclear maspin and loss of Ki-67 protein in breast cancer cell lines, while there was no effect in normal epithelial cells from breast. The anti

  9. The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote the proliferation of breast cancer cells

    International Nuclear Information System (INIS)

    Zhang, Yingyi; Zhao, Yu; Li, Leilei; Shen, Yu; Cai, Xiaoli; Zhang, Xiaodong; Ye, Lihong

    2013-01-01

    Highlights: •HBXIP is able to upregulate the expression of PDGFB in breast cancer cells. •HBXIP serves as a coactivator of activating transcription factor Sp1. •HBXIP stimulates the PDGFB promoter via activating transcription factor Sp1. •HBXIP promotes the proliferation of breast cancer cell via upregulating PDGFB. -- Abstract: We have reported that the oncoprotein hepatitis B virus X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. Previously, we showed that HBXIP was able to activate nuclear factor-κB (NF-κB) in breast cancer cells. As an oncogene, the platelet-derived growth factor beta polypeptide (PDGFB) plays crucial roles in carcinogenesis. In the present study, we found that both HBXIP and PDGFB were highly expressed in breast cancer cell lines. Interestingly, HBXIP was able to increase transcriptional activity of NF-κB through PDGFB, suggesting that HBXIP is associated with PDGFB in the cells. Moreover, HBXIP was able to upregulate PDGFB at the levels of mRNA, protein and promoter in the cells. Then, we identified that HBXIP stimulated the promoter of PDGFB through activating transcription factor Sp1. In function, HBXIP enhanced the proliferation of breast cancer cells through PDGFB in vitro. Thus, we conclude that HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote proliferation of breast cancer cells

  10. The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote the proliferation of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingyi; Zhao, Yu; Li, Leilei; Shen, Yu; Cai, Xiaoli [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [Department of Cancer Research, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ye, Lihong, E-mail: yelihong@nankai.edu.cn [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2013-05-03

    Highlights: •HBXIP is able to upregulate the expression of PDGFB in breast cancer cells. •HBXIP serves as a coactivator of activating transcription factor Sp1. •HBXIP stimulates the PDGFB promoter via activating transcription factor Sp1. •HBXIP promotes the proliferation of breast cancer cell via upregulating PDGFB. -- Abstract: We have reported that the oncoprotein hepatitis B virus X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. Previously, we showed that HBXIP was able to activate nuclear factor-κB (NF-κB) in breast cancer cells. As an oncogene, the platelet-derived growth factor beta polypeptide (PDGFB) plays crucial roles in carcinogenesis. In the present study, we found that both HBXIP and PDGFB were highly expressed in breast cancer cell lines. Interestingly, HBXIP was able to increase transcriptional activity of NF-κB through PDGFB, suggesting that HBXIP is associated with PDGFB in the cells. Moreover, HBXIP was able to upregulate PDGFB at the levels of mRNA, protein and promoter in the cells. Then, we identified that HBXIP stimulated the promoter of PDGFB through activating transcription factor Sp1. In function, HBXIP enhanced the proliferation of breast cancer cells through PDGFB in vitro. Thus, we conclude that HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote proliferation of breast cancer cells.

  11. Effects of biosurfactants on the viability and proliferation of human breast cancer cells.

    Science.gov (United States)

    Duarte, Cristina; Gudiña, Eduardo J; Lima, Cristovao F; Rodrigues, Ligia R

    2014-01-01

    Biosurfactants are molecules with surface activity produced by microorganisms that can be used in many biomedical applications. The anti-tumour potential of these molecules is being studied, although results are still scarce and few data are available regarding the mechanisms underlying such activity. In this work, the anti-tumour activity of a surfactin produced by Bacillus subtilis 573 and a glycoprotein (BioEG) produced by Lactobacillus paracasei subsp. paracasei A20 was evaluated. Both biosurfactants were tested against two breast cancer cell lines, T47D and MDA-MB-231, and a non-tumour fibroblast cell line (MC-3 T3-E1), specifically regarding cell viability and proliferation. Surfactin was found to decrease viability of both breast cancer cell lines studied. A 24 h exposure to 0.05 g l(-1) surfactin led to inhibition of cell proliferation as shown by cell cycle arrest at G1 phase. Similarly, exposure of cells to 0.15 g l(-1) BioEG for 48 h decreased cancer cells' viability, without affecting normal fibroblasts. Moreover, BioEG induced the cell cycle arrest at G1 for both breast cancer cell lines. The biosurfactant BioEG was shown to be more active than surfactin against the studied breast cancer cells. The results gathered in this work are very promising regarding the biosurfactants potential for breast cancer treatment and encourage further work with the BioEG glycoprotein.

  12. Differential effects of a complex organochlorine mixture on the proliferation of breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Aube, Michel, E-mail: 4aubem@videotron.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Larochelle, Christian, E-mail: christian.larochelle@inspq.qc.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Ayotte, Pierre, E-mail: pierre.ayotte@inspq.qc.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Laboratoire de Toxicologie, Institut national de sante publique du Quebec, 945 avenue Wolfe, Quebec, QC, Canada G1V 5B3 (Canada)

    2011-04-15

    Organochlorine compounds (OCs) are a group of persistent chemicals that accumulate in fatty tissues with age. Although OCs has been tested individually for their capacity to induce breast cancer cell proliferation, few studies examined the effect of complex mixtures that comprise compounds frequently detected in the serum of women. We constituted such an OC mixture containing 15 different components in environmentally relevant proportions and assessed its proliferative effects in four breast cancer cell lines (MCF-7, T47D, CAMA-1, MDAMB231) and in non-cancerous CV-1 cells. We also determined the capacity of the mixture to modulate cell cycle stage of breast cancer cells and to induce estrogenic and antiandrogenic effects using gene reporter assays. We observed that low concentrations of the mixture (100x10{sup 3} and 50x10{sup 3} dilutions) stimulated the proliferation of MCF-7 cells while higher concentrations (10x10{sup 3} and 5x10{sup 3} dilutions) had the opposite effect. In contrast, the mixture inhibited the proliferation of non-hormone-dependent cell lines. The mixture significantly increased the number of MCF-7 cells entering the S phase, an effect that was blocked by the antiestrogen ICI 182,780. Low concentrations of the mixture also caused an increase in CAMA-1 cell proliferation but only in the presence estradiol and dihydrotestosterone (p<0.05 at the 50x10{sup 3} dilution). DDT analogs and polychlorinated biphenyls all had the capacity to stimulate the proliferation of CAMA-1 cells in the presence of sex steroids. Reporter gene assays further revealed that the mixture and several of its constituents (DDT analogs, aldrin, dieldrin, {beta}-hexachlorocyclohexane, toxaphene) induced estrogenic effects, whereas the mixture and several components (DDT analogs, aldrin, dieldrin and PCBs) inhibited the androgen signaling pathway. Our results indicate that the complex OC mixture increases the proliferation of MCF-7 cells due to its estrogenic potential. The

  13. Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model

    International Nuclear Information System (INIS)

    Duursen, Majorie B.M. van; Smeets, Evelien E.J.W.; Rijk, Jeroen C.W.; Nijmeijer, Sandra M.; Berg, Martin van den

    2013-01-01

    Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of phytoestrogens. However, little is known about the potential interaction between these supplements and breast cancer treatment, especially aromatase inhibitors. In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the phytoestrogens on steroidogenesis. All tested supplements and GEN induced aromatase activity, while 8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in breast cancer patients can be provided. - Highlights: • Supplements containing phytoestrogens are commonly used by women with breast cancer. • Phytoestrogens alter steroidogenesis in a co-culture breast

  14. Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Duursen, Majorie B.M. van, E-mail: M.vanDuursen@uu.nl [Endocrine Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, PO Box 80177, 3508 TD, Utrecht (Netherlands); Smeets, Evelien E.J.W. [Endocrine Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, PO Box 80177, 3508 TD, Utrecht (Netherlands); Rijk, Jeroen C.W. [RIKILT - Institute for Food Safety, Wageningen UR, P.O. Box 230, 6700 AE, Wageningen (Netherlands); Nijmeijer, Sandra M.; Berg, Martin van den [Endocrine Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, PO Box 80177, 3508 TD, Utrecht (Netherlands)

    2013-06-01

    Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of phytoestrogens. However, little is known about the potential interaction between these supplements and breast cancer treatment, especially aromatase inhibitors. In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the phytoestrogens on steroidogenesis. All tested supplements and GEN induced aromatase activity, while 8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in breast cancer patients can be provided. - Highlights: • Supplements containing phytoestrogens are commonly used by women with breast cancer. • Phytoestrogens alter steroidogenesis in a co-culture breast

  15. The orphan nuclear receptor LRH-1 and ERα activate GREB1 expression to induce breast cancer cell proliferation.

    Directory of Open Access Journals (Sweden)

    Ashwini L Chand

    Full Text Available BACKGROUND: Liver Receptor Homolog 1 (LRH-1, NR5A2 is an orphan nuclear receptor that is over-expressed in cancers in tissues such as the breast, colon and pancreas. LRH-1 plays important roles in embryonic development, steroidogenesis and cholesterol homeostasis. In tumor cells, LRH-1 induces proliferation and cell cycle progression. High LRH-1 expression is demonstrated in breast cancers, positively correlating with ERα status and aromatase activity. LRH-1 dependent cellular mechanisms in breast cancer epithelial cells are poorly defined. Hence in the present study we investigated the actions of LRH-1 in estrogen receptor α (ERα positive breast cancer cells. RESULTS: The study aimed to investigate LRH-1 dependent mechanisms that promote breast cancer proliferation. We identified that LRH-1 regulated the expression of Growth Regulation by Estrogen in Breast Cancer 1 (GREB1 in MCF-7 and MDA-MB-231 cells. Over-expression of LRH-1 increased GREB1 mRNA levels while knockdown of LRH-1 reduced its expression. GREB1 is a well characterised ERα target gene, with three estrogen response elements (ERE located on its promoter. Chromatin immunoprecipitation studies provided evidence of the co-localisation of LRH-1 and ERα at all three EREs. With electrophoretic mobility shift assays, we demonstrated direct binding of LRH-1 to EREs located on GREB1 and Trefoil Factor 1 (TFF1, pS2 promoters. LRH-1 and ERα co-operatively activated transcription of ERE luciferase reporter constructs suggesting an overlap in regulation of target genes in breast cancer cells. Over-expression of LRH-1 resulted in an increase in cell proliferation. This effect was more pronounced with estradiol treatment. In the presence of ICI 182,780, an ERα antagonist, LRH-1 still induced proliferation. CONCLUSIONS: We conclude that in ER-positive breast cancer cells, LRH-1 promotes cell proliferation by enhancing ERα mediated transcription of target genes such as GREB-1. Collectively

  16. HSPC159 promotes proliferation and metastasis via inducing EMT and activating PI3K/Akt pathway in breast cancer.

    Science.gov (United States)

    Zheng, Jie; Zhang, Mengxue; Zhang, Liying; Ding, Xiaodi; Li, Wentong; Lu, Shijun

    2018-05-08

    HSPC159 is a novel human galectin-related protein and has been shown to involved in the carcinogenesis. Little is known about HSPC159 expression and function in breast cancer. Here we showed that HSPC159 was aberrantly expressed in both breast cancer cell lines and tumor tissues and that its expression was associated with poor prognosis of breast cancer patients. Using gain- and loss-of-function methods we found that HSPC159 enhanced breast cancer cells proliferation and metastasis in vitro and in vivo. Mechanistically, HSPC159 was found to induce epithelial-mesenchymal transition (EMT) and F-actin polymerization process of breast cancer cells. Moreover, HSPC159 promoted proliferation, migration and invasion through activating PI3K/Akt signaling pathway in breast cancer. In conclusion, our findings demonstrated that HSPC159 contributed to breast cancer progression via PI3K/Akt pathway and might serve as a potential therapeutic target for the treatment of breast cancer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. STAT5A-mediated NOX5-L expression promotes the proliferation and metastasis of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dho, So Hee [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Kim, Ji Young; Lee, Kwang-Pyo; Kwon, Eun-Soo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Lim, Jae Cheong [Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Kim, Chang-Jin [Department of Pathology, Soonchunhyang Medical Science Research Institute, Chonan 330-090 (Korea, Republic of); Jeong, Dongjun, E-mail: juny1024@sch.ac.kr [Department of Pathology, Soonchunhyang Medical Science Research Institute, Chonan 330-090 (Korea, Republic of); Kwon, Ki-Sun, E-mail: kwonks@kribb.re.kr [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 305-333 (Korea, Republic of)

    2017-02-01

    NADPH oxidase (NOX) generates reactive oxygen species (ROS) and has been suggested to mediate cell proliferation in some cancers. Here, we show that an increase in the expression of NOX5 long form (NOX5-L) is critical for tumor progression in breast tumor tissues. Immunostaining of clinical samples indicated that NOX5 was overexpressed in 41.1% of breast ductal carcinoma samples. NOX5-L depletion consistently suppressed cell proliferation, invasion, and migration in vitro. Antibody-mediated neutralization of NOX5-L attenuated tumor progression in a mouse xenograft model. Promoter analysis revealed that NOX5-L expression is regulated by STAT5A in breast cancer cells. Based on our novel findings, we suggest that inhibition of NOX5-L may be a promising therapeutic strategy that exerts anti-cancer effects via the modulation of ROS-mediated cell signaling. - Highlights: • The ROS-generating protein, NOX5-L, determines cellular proliferation and metastasis in subset of breast tumor. • Tumor growth was attenuated by the treatment of anti-NOX5-L antibody in a xenograft model. • NOX5-L expression is transcriptionally regulated by STAT5A in breast cancer cells.

  18. Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ryota Domura

    2017-06-01

    Full Text Available The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments and different stiffness of the polymeric substrates (poly(l-lactic acid and poly(ε-caprolactone, PLLA and PCL, respectively as well as collagen substrates (coat and gel to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7. The morphological spreading parameter (nucleus/cytoplasm area ratio induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC50 of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

  19. Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells.

    Science.gov (United States)

    Domura, Ryota; Sasaki, Rie; Ishikawa, Yuma; Okamoto, Masami

    2017-06-06

    The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (poly(l-lactic acid) and poly(ε-caprolactone), PLLA and PCL, respectively) as well as collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter (nucleus/cytoplasm area ratio) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC 50 ) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

  20. Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Xin; Lyu, Pengwei; Gu, Yuanting; Li, Lin; Li, Jingruo; Wang, Yan; Zhang, Linfeng [Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Fu, Chao [Department of Ultrasonography, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Cao, Zhang, E-mail: zzzhangcao@126.com [Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China)

    2015-08-28

    Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did not alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser{sup 461}, along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breast cancers. • Shh promoted glucose utilization, lactate production, and cell proliferation. • Shh did not alter PFKFB3 expression but augmented PFKFB3 phosphorylation on ser461. • Shh acts on PFKFB3 phosphorylation via Smo and p38 MAPK/MK2.

  1. Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation

    International Nuclear Information System (INIS)

    Ge, Xin; Lyu, Pengwei; Gu, Yuanting; Li, Lin; Li, Jingruo; Wang, Yan; Zhang, Linfeng; Fu, Chao; Cao, Zhang

    2015-01-01

    Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did not alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser 461 , along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breast cancers. • Shh promoted glucose utilization, lactate production, and cell proliferation. • Shh did not alter PFKFB3 expression but augmented PFKFB3 phosphorylation on ser461. • Shh acts on PFKFB3 phosphorylation via Smo and p38 MAPK/MK2

  2. Overexpression of miR-206 suppresses glycolysis, proliferation and migration in breast cancer cells via PFKFB3 targeting

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Xin; Lyu, Pengwei; Cao, Zhang; Li, Jingruo; Guo, Guangcheng; Xia, Wanjun; Gu, Yuanting, E-mail: zzyuantinggu@126.com

    2015-08-07

    miRNAs, sorting as non-coding RNAs, are differentially expressed in breast tumor and act as tumor promoters or suppressors. miR-206 could suppress the progression of breast cancer, the mechanism of which remains unclear. The study here was aimed to investigate the effect of miR-206 on human breast cancers. We found that miR-206 was down-regulated while one of its predicted targets, 6-Phosphofructo-2-kinase (PFKFB3) was up-regulated in human breast carcinomas. 17β-estradiol dose-dependently decreased miR-206 expression as well as enhanced PFKFB3 mRNA and protein expression in estrogen receptor α (ERα) positive breast cancer cells. Furthermore, we identified that miR-206 directly interacted with 3′-untranslated region (UTR) of PFKFB3 mRNA. miR-206 modulated PFKFB3 expression in MCF-7, T47D and SUM159 cells, which was influenced by 17β-estradiol depending on ERα expression. In addition, miR-206 overexpression impeded fructose-2,6-bisphosphate (F2,6BP) production, diminished lactate generation and reduced cell proliferation and migration in breast cancer cells. In conclusion, our study demonstrated that miR-206 regulated PFKFB3 expression in breast cancer cells, thereby stunting glycolysis, cell proliferation and migration. - Highlights: • miR-206 was down-regulated and PFKFB3 was up-regulated in human breast carcinomas. • 17β-estradiol regulated miR-206 and PFKFB3 expression in ERα+ cancer cells. • miR-206directly interacted with 3′-UTR of PFKFB3 mRNA. • miR-206 fructose-2,6-bisphosphate (F2,6BP) impeded production and lactate generation. • miR-206 reduced cell proliferation and migration in breast cancer cells.

  3. Long Noncoding RNA HOTAIR Modulates MiR-206-mediated Bcl-w Signaling to Facilitate Cell Proliferation in Breast Cancer.

    Science.gov (United States)

    Ding, Wei; Ren, Jin; Ren, Hui; Wang, Dan

    2017-12-08

    LncRNA HOX transcript antisense RNA (HOTAIR) is involved in lots of cancers. The pro-survival protein Bcl-w is frequently found in cancer development. However, the effect of HOTAIR on Bcl-w in breast cancer is not well documented. In this study, we first evaluated the correlation between HOTAIR level and Bcl-w expression in clinical breast cancer tissues. We observed that the expression levels of Bcl-w were much higher in the breast cancer samples than that in their paired noncancerous tissues. Moreover, the levels of HOTAIR were positively associated with those of Bcl-w in clinical breast cancer samples. As expected, we observed that HOTAIR was able to up-regulate the expression of Bcl-w in breast cancer cells. Mechanistically, we found that miR-206 was capable of inhibiting the expression of Bcl-w by directly binding to the 3'UTR of Bcl-w mRNA. Interestingly, HOTAIR could increase the expression of Bcl-w through sequestering miR-206 at post-transcriptional level. Functionally, our data showed that HOTAIR-induced Bcl-w by miR-206 facilitated the proliferation of breast cancer cells. Thus, we conclude that HOTAIR up-regulates Bcl-w to enhance cell proliferation through sequestering miR-206 in breast cancer. Our finding provides new insights into the mechanism of breast cancer mediated by HOTAIR.

  4. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yongguo, E-mail: 1138303166@qq.com [Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Lu, Jianwei, E-mail: jianwei2010077@163.com [Cancer Hospital of Jiangsu Province, Nanjing, Jiangsu (China); Zhou, Jing, E-mail: 2310848@163.com [Department of Oncology, Taizhou People’ Hospital, Taizhou, Jiangsu (China); Tan, Xueming, E-mail: 843039795@qq.com [Department of Gastroenterology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); He, Ye, E-mail: 2825636@qq.com [Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Ding, Jie, E-mail: 9111165@qq.com [Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Tian, Yun, E-mail: 1815857@qq.com [Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Wang, Li, E-mail: 2376737@qq.com [Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Wang, Keming, E-mail: wkmys@sohu.com [Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China)

    2014-04-04

    Highlights: • First, we have shown that upregulated of the Loc554202 in breast cancer tissues. • Second, we demonstrated the function of Loc554202 in breast cancer cell. • Finally, we demonstrated that LOC554202 knockdown could inhibit tumor growth in vivo. - Abstract: Data derived from massive cloning and traditional sequencing methods have revealed that long non-coding RNAs (lncRNA) play important roles in the development and progression of cancer. Although many studies suggest that the lncRNAs have different cellular functions, many of them are not yet to be identified and characterized for the mechanism of their functions. To address this question, we assay the expression level of lncRNAs–Loc554202 in breast cancer tissues and find that Loc554202 is significantly increased compared with normal control, and associated with advanced pathologic stage and tumor size. Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis.

  5. IL-7 splicing variant IL-7δ5 induces human breast cancer cell proliferation via activation of PI3K/Akt pathway

    International Nuclear Information System (INIS)

    Pan, Deshun; Liu, Bing; Jin, Xiaobao; Zhu, Jiayong

    2012-01-01

    Highlights: ► This study confirms the role of IL-7δ5 in breast cancer cell proliferation. ► IL-7δ5 promotes breast cancer cell proliferation and cell cycle progression. ► IL-7δ5 promotes cell proliferation via activation of PI3K/Akt pathway. -- Abstract: Various tumor cells express interleukin 7 (IL-7) and IL-7 variants. IL-7 has been confirmed to stimulate solid tumor cell proliferation. However, the effect of IL-7 variants on tumor cell proliferation remains unclear. In this study, we evaluated the role of IL-7δ5 (an IL-7 variant lacking exon 5) on proliferation and cell cycle progression of human MDA-MB-231 and MCF-7 breast cancer cells. The results showed that IL-7δ5 promoted cell proliferation and cell cycle progression from G1 phase to G2/M phase, associated with upregulation of cyclin D1 expression and the downregulation of p27 kip1 expression. Mechanistically, we found that IL-7δ5 induced the activation of Akt. Inhibition of PI3K/Akt pathway by LY294002 reversed the proliferation and cell cycle progression of MDA-MB-231 and MCF-7 cells induced by IL-7δ5. In conclusion, our findings demonstrate that IL-7δ5 variant induces human breast cancer cell proliferation and cell cycle progression via activation of PI3K/Akt pathway. Thus, IL-7δ5 may be a potential target for human breast cancer therapeutics intervention.

  6. A naringenin–tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hatkevich, Talia; Ramos, Joseph; Santos-Sanchez, Idalys; Patel, Yashomati M., E-mail: ympatel@uncg.edu

    2014-10-01

    Since over 60% of breast cancers are estrogen receptor positive (ER+), many therapies have targeted the ER. The ER is activated by both estrogen binding and phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been successful they do not target the growth factor promoting phosphorylation of the ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase, (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in breast cancer cells and are associated with poor prognosis. Thus targeting multiple cellular proliferation and survival pathways at the onset of treatment is critical for the development of more effective therapies. The grapefruit flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways. Previous studies examining either Nar or Tam used charcoal-stripped serum which removed estrogen as well as other factors. We wanted to use serum containing medium in order to retain all the potential inducers of cell proliferation so as not to exclude any targets of Nar. Here we show that a Nar–Tam combination is more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells. We demonstrate that a Nar–Tam combination impaired cellular proliferation and viability to a greater extent than either component alone in MCF-7 cells. Furthermore, the use of a Nar–Tam combination requires lower concentrations of both compounds to achieve the same effects on proliferation and viability. Nar may function by inhibiting both PI3K and MAPK pathways as well as localizing ERα to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar–Tam combination induces apoptosis and impairs proliferation signaling to a greater extent than either compound alone. These studies provide critical information for understanding the molecular mechanisms involved in cell proliferation and apoptosis in breast cancer cells. - Highlights: • Nar–Tam impairs cell viability more effectively than

  7. A naringenin–tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Hatkevich, Talia; Ramos, Joseph; Santos-Sanchez, Idalys; Patel, Yashomati M.

    2014-01-01

    Since over 60% of breast cancers are estrogen receptor positive (ER+), many therapies have targeted the ER. The ER is activated by both estrogen binding and phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been successful they do not target the growth factor promoting phosphorylation of the ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase, (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in breast cancer cells and are associated with poor prognosis. Thus targeting multiple cellular proliferation and survival pathways at the onset of treatment is critical for the development of more effective therapies. The grapefruit flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways. Previous studies examining either Nar or Tam used charcoal-stripped serum which removed estrogen as well as other factors. We wanted to use serum containing medium in order to retain all the potential inducers of cell proliferation so as not to exclude any targets of Nar. Here we show that a Nar–Tam combination is more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells. We demonstrate that a Nar–Tam combination impaired cellular proliferation and viability to a greater extent than either component alone in MCF-7 cells. Furthermore, the use of a Nar–Tam combination requires lower concentrations of both compounds to achieve the same effects on proliferation and viability. Nar may function by inhibiting both PI3K and MAPK pathways as well as localizing ERα to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar–Tam combination induces apoptosis and impairs proliferation signaling to a greater extent than either compound alone. These studies provide critical information for understanding the molecular mechanisms involved in cell proliferation and apoptosis in breast cancer cells. - Highlights: • Nar–Tam impairs cell viability more effectively than

  8. A recombined fusion protein PTD-Grb2-SH2 inhibits the proliferation of breast cancer cells in vitro.

    Science.gov (United States)

    Yin, Jikai; Cai, Zhongliang; Zhang, Li; Zhang, Jian; He, Xianli; Du, Xilin; Wang, Qing; Lu, Jianguo

    2013-03-01

    The growth factor receptor bound protein 2 (Grb2) is one of the affirmative targets for cancer therapy, especially for breast cancer. In this study, we hypothesized the Src-homology 2 (SH2) domain in Grb2 may serve as a competitive protein-binding agent to interfere with the proliferation of breast cancer cells in vitro. We designed, constructed, expressed and purified a novel fusion protein containing the protein transduction domain (PTD) and Grb2-SH2 domain (we named it after PTD-Grb2-SH2). An immunofluorescence assay was used to investigate the location of PTD-Grb2-SH2 in cells. MTT assay and EdU experiments were applied to detect the proliferation of breast cancer cells. The ultra-structure was observed using transmission electron microscopy. Flow cytometry was used to determine the cytotoxicity of PTD-Grb2-SH2 on cell proliferation. We successfully obtained the PTD-Grb2-SH2 fusion protein in soluble form using a prokaryotic expression system. The new fusion protein successfully passed through both the cellular and nuclear membranes of breast cancer cells. The MTT assay showed that PTD-Grb2-SH2 exhibited significant toxicity to breast cancer cells in a dose- and time-dependent manner in vitro. EdU identified the decreased proliferation rates in treated MDA-MB-231 and SK-BR-3 cells. Observation by transmission electron microscopy and flow cytometry further confirmed the cytotoxicity as apoptosis. Our results show that the HIV1-TAT domain is a useful tool for transporting a low molecular weight protein across the cell membrane in vitro. The PTD-Grb2-SH2 may be a novel agent for breast cancer therapy.

  9. Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner.

    Science.gov (United States)

    David, Diana; Jagadeeshan, Sankar; Hariharan, Ramkumar; Nair, Asha Sivakumari; Pillai, Radhakrishna Madhavan

    2014-01-01

    Smurf2 is a member of the HECT family of E3 ubiquitin ligases that play important roles in determining the competence of cells to respond to TGF- β/BMP signaling pathway. However, besides TGF-β/BMP pathway, Smurf2 regulates a repertoire of other signaling pathways ranging from planar cell polarity during embryonic development to cell proliferation, migration, differentiation and senescence. Expression of Smurf2 is found to be dysregulated in many cancers including breast cancer. The purpose of the present study is to examine the effect of Smurf2 knockdown on the tumorigenic potential of human breast cancer cells emphasizing more on proliferative signaling pathway. siRNAs targeting different regions of the Smurf2 mRNA were employed to knockdown the expression of Smurf2. The biological effects of synthetic siRNAs on human breast cancer cells were investigated by examining the cell proliferation, migration, invasion, focus formation, anchorage-independent growth, cell cycle arrest, and cell cycle and cell proliferation related protein expressions upon Smurf2 silencing. Smurf2 silencing in human breast cancer cells resulted in a decreased focus formation potential and clonogenicity as well as in vitro cell migration/invasion capabilities. Moreover, knockdown of Smurf2 suppressed cell proliferation. Cell cycle analysis showed that the anti-proliferative effect of Smurf2 siRNA was mediated by arresting cells in the G0/G1 phase, which was caused by decreased expression of cyclin D1and cdk4, followed by upregulation p21 and p27. Furthermore, we demonstrated that silencing of Smurf2 downregulated the proliferation of breast cancer cells by modulating the PI3K- PTEN-AKT-FoxO3a pathway via the scaffold protein CNKSR2 which is involved in RAS-dependent signaling pathways. The present study provides the first evidence that silencing Smurf2 using synthetic siRNAs can regulate the tumorigenic properties of human breast cancer cells in a CNKSR2 dependent manner. Our results

  10. H19 lncRNA mediates 17β-estradiol-induced cell proliferation in MCF-7 breast cancer cells.

    Science.gov (United States)

    Sun, Hong; Wang, Guo; Peng, Yan; Zeng, Ying; Zhu, Qiong-Ni; Li, Tai-Lin; Cai, Jia-Qin; Zhou, Hong-Hao; Zhu, Yuan-Shan

    2015-06-01

    Estrogen plays a critical role in breast cancer development and progression. However, the mechanism involved in the promotion of breast cancer development and progression by estrogen remains unclear although it has been intensively studied. In the present study, we investigated the estrogen inducibility and functional significance of H19 lncRNA in breast cancer cells and tumor tissues. The screening of 83 disease-related long non-coding RNAs (lncRNAs) revealed that H19 lncRNA was much higher in estrogen receptor (ER)-positive MCF-7 breast cancer cells than in ER-negative MDA-MB-231 cells. 17β-estradiol produced a dose- and time-dependent induction of H19 expression in MCF-7 cells, which was mediated via ERα as evident by the blockade of this 17β-estradiol effect with ICI 182780, a specific ER antagonist and knockdown of ERα using specific RNAi. Moreover, knockdown of H19 lncRNA decreased cell survival and blocked estrogen-induced cell growth while overexpression of H19 lncRNA stimulated cell proliferation. Quantitation of H19 lncRNA in human breast cancer tissues showed that the level of H19 lncRNA was >10-fold higher in ER-positive than in ER-negative tumor tissues. These results suggest that H19 is an estrogen-inducible gene and plays a key role in cell survival and in estrogen-induced cell proliferation in MCF-7 cells, indicating that H19 lncRNA may serve as a biomarker for breast cancer diagnosis and progression, and as a valuable target for breast cancer therapy.

  11. miR-625 suppresses cell proliferation and migration by targeting HMGA1 in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Wen-bin; Zhong, Cai-neng; Luo, Xun-peng; Zhang, Ya-yuan; Zhang, Gui-ying [Department of Breast Surgery, Second Clinical Medical College of Jinan University, Shenzhen People' s Hospital, Shenzhen, Guangdong Province (China); Zhou, Dong-xian, E-mail: 1072241978@qq.com [Department of Breast Surgery, Second Clinical Medical College of Jinan University, Shenzhen People' s Hospital, Shenzhen, Guangdong Province (China); Liu, Li-ping, E-mail: leoliping@aliyun.com [Department of Hepatobiliary and Pancreas Surgery, Second Clinical Medical College of Jinan University, Shenzhen People' s Hospital, Shenzhen, Guangdong Province (China)

    2016-02-19

    Dysregulation of microRNA contributes to the high incidence and mortality of breast cancer. Here, we show that miR-625 was frequently down-regulated in breast cancer. Decrease of miR-625 was closely associated with estrogen receptor (P = 0.004), human epidermal growth factor receptor 2 (P = 0.003) and clinical stage (P = 0.001). Kaplan–Meier and multivariate analyses indicated miR-625 as an independent factor for unfavorable prognosis (hazard ratio = 2.654, 95% confident interval: 1.300–5.382, P = 0.007). Re-expression of miR-625 impeded, whereas knockdown of miR-625 enhanced cell viabilities and migration abilities in breast cancer cells. HMGA1 was confirmed as a direct target of miR-625. The expressions of HMGA1 mRNA and protein were induced by miR-625 mimics, but reduced by miR-625 inhibitor. Re-introduction of HMGA1 in cells expressing miR-625 distinctly abrogated miR-625-mediated inhibition of cell growth. Taken together, our data demonstrate that miR-625 suppresses cell proliferation and migration by targeting HMGA1 and suggest miR-625 as a promising prognostic biomarker and a potential therapeutic target for breast cancer. - Highlights: • miR-625 expression was significantly decreased in breast cancer. • Decrease of miR-625 was associated with poor clinical outcomes and unfavorable overall survival. • miR-625 overexpression inhibits cell proliferation and migration in vitro. • miR-625 directly targets and suppresses the expression of HMGA1.

  12. GP88 (PC-Cell Derived Growth Factor, progranulin stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

    Directory of Open Access Journals (Sweden)

    Sabnis Gauri

    2011-06-01

    Full Text Available Abstract Background Aromatase inhibitors (AI that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+ breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88, also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells Methods We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. Results GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Conclusion Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.

  13. Long non-coding RNA TUG1 promotes cell proliferation and metastasis in human breast cancer.

    Science.gov (United States)

    Li, Teng; Liu, Yun; Xiao, Haifeng; Xu, Guanghui

    2017-07-01

    Long non-coding RNAs (LncRNAs) utilize a wide variety of mechanisms to regulate RNAs or proteins on the transcriptional or post-transcriptional levels. Accumulating studies have identified numerous LncRNAs to exert critical effects on different physiological processes, genetic disorders, and human diseases. Both clinical tissues from breast cancer patients and cultured cells were used for the qRT-PCR analysis. Specific siRNAs were included to assess the roles of TUG1 with cell viability assay, transwell assay, and cell apoptosis assay, respectively. The expression of TUG1 was enhanced in breast cancerous tissues and in highly invasive breast cancer cell lines and was associated with clinical variables, including tumor size, distant metastasis and TNM staging. Knockdown of TUG1 significantly slowed down cell proliferation, cell migration, and invasion in breast cancer cell lines MDA-MB-231 and MDA-MB-436. In addition, cell apoptotic rate was shown to increase upon siTUG1 treatment as evidenced by increases of the activities of caspase-3 and caspase-9. The identification of TUG1 as a critical mediator of breast cancer progression implied that it might serve as a biomarker for the diagnosis and treatment of breast cancer in clinic.

  14. Lentivirus mediated RNA interference of EMMPRIN (CD147) gene inhibits the proliferation, matrigel invasion and tumor formation of breast cancer cells.

    Science.gov (United States)

    Yang, Jing; Wang, Rong; Li, Hongjiang; Lv, Qing; Meng, Wentong; Yang, Xiaoqin

    2016-07-08

    Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147), a glycoprotein enriched on the plasma membrane of tumor cells, promotes proliferation, invasion, metastasis, and survival of malignant tumor cells. In this study, we sought to examine the expression of EMMPRIN in breast tumors, and to identify the potential roles of EMMPRIN on breast cancer cells. EMMPRIN expression in breast cancer tissues was assessed by immunohistochemistry. We used a lentivirus vector-based RNA interference (RNAi) approach expressing short hairpin RNA (shRNA) to knockdown EMMPRIN gene in breast cancer cell lines MDA-MB-231 and MCF-7. In vitro, Cell proliferative, invasive potential were determined by Cell Counting Kit (CCK-8), cell cycle analysis and matrigel invasion assay, respectively. In vivo, tumorigenicity was monitored by inoculating tumor cells into breast fat pad of female nude mice. EMMPRIN was over-expressed in breast tumors and breast cancer cell lines. Down-regulation of EMMPRIN by lentivirus vector-based RNAi led to decreased cell proliferative, decreased matrigel invasion in vitro, and attenuated tumor formation in vivo. High expression of EMMPRIN plays a crucial role in breast cancer cell proliferation, matrigel invasion and tumor formation.

  15. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

    Science.gov (United States)

    Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

    2014-01-01

    The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

  16. miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

    International Nuclear Information System (INIS)

    Zhang, Yunda; Xu, Guoxing; Liu, Gang; Ye, Yongzhi; Zhang, Chuankai; Fan, Chuannan; Wang, Haibin; Cai, Huali; Xiao, Rui; Huang, Zhengjie; Luo, Qi

    2016-01-01

    miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2 is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.

  17. miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yunda [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 (China); Xu, Guoxing [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 (China); Liu, Gang; Ye, Yongzhi [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Zhang, Chuankai [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 (China); Fan, Chuannan [State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 (China); Wang, Haibin; Cai, Huali; Xiao, Rui [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 (China); Huang, Zhengjie, E-mail: huangzhengjie@xmu.edu.cn [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 (China); Luo, Qi, E-mail: luoqixmzsh@126.com [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 (China)

    2016-08-05

    miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2 is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.

  18. New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.

    Directory of Open Access Journals (Sweden)

    Ghada Allan

    Full Text Available sp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4, cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21(Waf1/Cip1. In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer.

  19. Protocadherin-7 induces bone metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ai-Min [Department of Orthopedics, The 5th Central Hospital of Tianjin, Tianjin (China); Tian, Ai-Xian [Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Zhang, Rui-Xue [Department of Clinical Laboratory Diagnosis, Tianjin Medical University, Tianjin (China); Ge, Jie [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Sun, Xuan [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Cao, Xu-Chen, E-mail: caoxuch@126.com [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-07-05

    Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.

  20. Protocadherin-7 induces bone metastasis of breast cancer

    International Nuclear Information System (INIS)

    Li, Ai-Min; Tian, Ai-Xian; Zhang, Rui-Xue; Ge, Jie; Sun, Xuan; Cao, Xu-Chen

    2013-01-01

    Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer

  1. ERK/CANP rapid signaling mediates 17β-estradiol-induced proliferation of human breast cancer cell line MCF-7 cells.

    Science.gov (United States)

    Wang, Guo-Sheng; Huang, Yan-Gang; Li, Huan; Bi, Shi-Jie; Zhao, Jin-Long

    2014-01-01

    17β-estradiol (E2) exerts its functions through both genomic and non-genomic signaling pathways. Because E2 is important in breast cancer development, we investigated whether its actions in promoting breast cancer cell proliferation occur through the non-genomic signaling pathway via extracellular signal-regulated kinase 1/2 (ERK1/2)/calcium-activated neutral protease (CANP). MCF-7 breast cancer cells were treated with ERKl/2 inhibitor (PD98059) or CANP inhibitor (calpeptin) before exposure to 1×10(-8) M E2. MTT colorimetry and flow cytometry were used to analyze effects on cell proliferation and cell cycle progression, respectively. Expression of phosphorylated-ERK (p-ERK), total ERK, and Capn4 proteins were assessed by Western blotting. Cell proliferation increased in cells treated with E2 for 24 h (P<0.05), and the proportion of cells in G0/G1 was decreased, accompanied by accelerated G1/S. Calpeptin pre-treatment significantly inhibited the E2-induced proliferation of MCF-7 cells (P<0.05), while also ameliorating the effects of E2 on cell cycle progression. Further, expression of p-ERK was rapidly up-regulated (after 10 min) by E2 (P<0.05), an effect that persisted 16 h after E2 exposure but which was significantly inhibited by PD98059 (P<0.05). Finally, expression of Capn4 protein was rapidly up-regulated in E2-exposed cells (P<0.05), but this change was significantly inhibited by PD98059 or calpeptin (P<0.05) pre-treatment. Thus, the rapid, non-genomic ERK/CANP signaling pathway mediates E2-induced proliferation of human breast cancer cells.

  2. Intratumor heterogeneity of DCE-MRI reveals Ki-67 proliferation status in breast cancer

    Science.gov (United States)

    Cheng, Hu; Fan, Ming; Zhang, Peng; Liu, Bin; Shao, Guoliang; Li, Lihua

    2018-03-01

    Breast cancer is a highly heterogeneous disease both biologically and clinically, and certain pathologic parameters, i.e., Ki67 expression, are useful in predicting the prognosis of patients. The aim of the study is to identify intratumor heterogeneity of breast cancer for predicting Ki-67 proliferation status in estrogen receptor (ER)-positive breast cancer patients. A dataset of 77 patients was collected who underwent dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) examination. Of these patients, 51 were high-Ki-67 expression and 26 were low-Ki-67 expression. We partitioned the breast tumor into subregions using two methods based on the values of time to peak (TTP) and peak enhancement rate (PER). Within each tumor subregion, image features were extracted including statistical and morphological features from DCE-MRI. The classification models were applied on each region separately to assess whether the classifiers based on features extracted from various subregions features could have different performance for prediction. An area under a receiver operating characteristic curve (AUC) was computed using leave-one-out cross-validation (LOOCV) method. The classifier using features related with moderate time to peak achieved best performance with AUC of 0.826 than that based on the other regions. While using multi-classifier fusion method, the AUC value was significantly (P=0.03) increased to 0.858+/-0.032 compare to classifier with AUC of 0.778 using features from the entire tumor. The results demonstrated that features reflect heterogeneity in intratumoral subregions can improve the classifier performance to predict the Ki-67 proliferation status than the classifier using features from entire tumor alone.

  3. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells

    International Nuclear Information System (INIS)

    Garcia-Becerra, Rocio; Diaz, Lorenza; Camacho, Javier; Barrera, David; Ordaz-Rosado, David; Morales, Angelica; Ortiz, Cindy Sharon; Avila, Euclides; Bargallo, Enrique; Arrecillas, Myrna; Halhali, Ali; Larrea, Fernando

    2010-01-01

    Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-a-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

  4. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Becerra, Rocio [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Diaz, Lorenza, E-mail: lorenzadiaz@gmail.com [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Camacho, Javier [Department of Pharmacology, Centro de Investigacion y de Estudios Avanzados, Instituto Politecnico Nacional, Av. Instituto Politecnico Nacional 2508, San Pedro Zacatenco 07360, Mexico, D.F. (Mexico); Barrera, David; Ordaz-Rosado, David; Morales, Angelica [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Ortiz, Cindy Sharon [Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Avila, Euclides [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Bargallo, Enrique [Department of Breast Tumors, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Arrecillas, Myrna [Department of Pathology, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Halhali, Ali; Larrea, Fernando [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)

    2010-02-01

    Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-a-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

  5. Cell-specific regulation of proliferation by Ano1/TMEM16A in breast cancer with different ER, PR, and HER2 status.

    Science.gov (United States)

    Wu, Huizhe; Wang, Hui; Guan, Shu; Zhang, Jing; Chen, Qiuchen; Wang, Xiaodong; Ma, Ke; Zhao, Pengfei; Zhao, Haishan; Yao, Weifan; Jin, Feng; Xiao, Qinghuan; Wei, Minjie

    2017-10-17

    The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many tumors. However, conflicting data exist regarding the role of Ano1 in cell proliferation. Here, we performed immunohistochemistry to investigate the expression of Ano1 and Ki67 in 403 patients with breast cancer, and analyzed the association between the expression of Ano1 and Ki67 in breast cancer subtypes categorized according to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Ano1 expression was negatively correlated with Ki67 expression. Ano1 overexpression more frequently occurred in ER-positive or HER2-negative patients with the low expression of Ki67. Ano1 overexpression was associated with longer overall survival (OS) in breast cancer with the low expression of Ki67, especially in ER-positive, PR-positive, and HER2-negative breast cancer. Multivariate Cox regression analysis showed that Ano1 overexpression was a prognostic factor for longer overall survival in ER-positive, PR-positive, or HER2-negative patients with the low expression of Ki67. Furthermore, Ano1 promoted cell proliferation in ER-positive, PR-positive, and HER2-negative MCF7 cells, but inhibited cell proliferation in ER-negative, PR-negative, and HER2-negative MDA-MB-435S cells. Our findings suggest that Ano1 may differentially regulate cell proliferation in a subtype of breast cancer defined by ER, PR, and HER2. Combined expression of Ano1 and Ki67 may be used for predicting clinical outcomes of breast cancer patients with different subtypes of ER, PR, and HER2.

  6. Transforming growth factor β-activated kinase 1 inhibitor suppresses the proliferation in triple-negative breast cancer through TGF-β/TGFR pathway.

    Science.gov (United States)

    Zhang, Liangyu; Fu, Zelong; Li, Xia; Tang, Haitao; Luo, Jiesi; Zhang, Dehui; Zhuang, Yongzhi; Han, Zhiyang; Yin, Mingzhu

    2017-09-01

    Breast cancer is one of the most invasive cancer types in female population. The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. However, the fundamental role of TAK1 for triple-negative breast cancer (TNBC) progression and the effect of potential anti-TAK1 drug candidate needs to be further evaluated. Herein, we focused on the role of TAK1 in human breast cancer cells, and we hypothesized that the inhibition of TAK1 activation can repress the growth of human TNBC cells. We found that the TAK1 is robustly activated within cancer cell population of clinic-derived TNBC samples and the human breast cancer cell lines in culture. Furthermore, we determined the effect of 5Z-7-oxozeaenol (5Z-O), a TAK1-specific small molecule inhibitor, on proliferation of human TNBC cell line. 5Z-O treatment significantly suppressed the proliferation of human TNBC cells. Collectively, these demonstrate the role of TAK1 in human breast cancer and the antiproliferate effect of TAK1 inhibitor. Our study sets the stage for further research on TAK1 as a promising target for development of anti-TNBC drugs and therapeutic strategies. © 2017 John Wiley & Sons A/S.

  7. The Paraguayan Rhinella toad venom: Implications in the traditional medicine and proliferation of breast cancer cells.

    Science.gov (United States)

    Schmeda-Hirschmann, Guillermo; Gomez, Celeste Vega; Rojas de Arias, Antonieta; Burgos-Edwards, Alberto; Alfonso, Jorge; Rolon, Miriam; Brusquetti, Francisco; Netto, Flavia; Urra, Félix A; Cárdenas, César

    2017-03-06

    Toads belonging to genus Rhinella are used in Paraguayan traditional medicine to treat cancer and skin infections. The objective of the study was to determine the composition of venoms obtained from three different Paraguayan Rhinella species, to establish the constituents of a preparation sold in the capital city of Paraguay to treat cancer as containing the toad as ingredient, to establish the effect of the most active Rhinella schneideri venom on the cell cycle using human breast cancer cells and to assess the antiprotozoal activity of the venoms. The venom obtained from the toads parotid glands was analyzed by HPLC-MS-MS. The preparation sold in the capital city of Paraguay to treat cancer that is advertised as made using the toad was analyzed by HPLC-MS-MS. The effect of the R. schneideri venom and the preparation was investigated on human breast cancer cells. The antiprotozoal activity was evaluated on Leishmania braziliensis, L. infantum and murine macrophages. From the venoms of R. ornata, R. schneideri and R. scitula, some 40 compounds were identified by spectroscopic and spectrometric means. Several minor constituents are reported for the first time. The preparation sold as made from the toad did not contained bufadienolides or compounds that can be associated with the toad but plant compounds, mainly phenolics and flavonoids. The venom showed activity on human breast cancer cells and modified the cell cycle proliferation. The antiprotozoal effect was higher for the R. schneideri venom and can be related to the composition and relative ratio of constituents compared with R. ornata and R. scitula. The preparation sold in the capital city of Paraguay as containing the toad venom, used popularly to treat cancer did not contain the toad venom constituents. Consistent with this, this preparation was inactive on proliferation of human breast cancer cells. In contrast, the toad venoms of Rhinella species altered the cell cycle progression, affecting the

  8. Lactate dehydrogenase downregulation mediates the inhibitory effect of diallyl trisulfide on proliferation, metastasis, and invasion in triple-negative breast cancer.

    Science.gov (United States)

    Cheng, Shi-Yann; Yang, Yao-Chih; Ting, Kuan-Lun; Wen, Su-Ying; Viswanadha, Vijaya Padma; Huang, Chih-Yang; Kuo, Wei-Wen

    2017-04-01

    The Warburg effect plays a critical role in tumorigenesis, suggesting that specific agents targeting Warburg effect key proteins may be a promising strategy for cancer therapy. Previous studies have shown that diallyl trisulfide (DATS) inhibits proliferation of breast cancer cells by inducing apoptosis in vitro and in vivo. However, whether the Warburg effect is involved with the apoptosis-promoting action of DATS is unclear. Here, we show that the action of DATS is associated with downregulation of lactate dehydrogenase A (LDHA), an essential protein of the Warburg effect whose upregulation is closely related to tumorigenesis. Interestingly, inhibition of the Warburg effect by DATS in breast cancer cells did not greatly affect normal cells. Furthermore, DATS inhibited growth of breast cancer cells, particularly in MDA-MB-231, a triple-negative breast cancer (TNBC) cell, and reduced proliferation and migration; invasion was reversed by over-expression of LDHA. These data suggest that DATS inhibits breast cancer growth and aggressiveness through a novel pathway targeting the key enzyme of the Warburg effect. Our study shows that LDHA downregulation is involved in the apoptotic effect of DATS on TNBC. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1390-1398, 2017. © 2016 Wiley Periodicals, Inc.

  9. Role of KCNMA1 in breast cancer.

    Directory of Open Access Journals (Sweden)

    Martin Oeggerli

    Full Text Available KCNMA1 encodes the α-subunit of the large conductance, voltage and Ca(2+-activated (BK potassium channel and has been reported as a target gene of genomic amplification at 10q22 in prostate cancer. To investigate the prevalence of the amplification in other human cancers, the copy number of KCNMA1 was analyzed by fluorescence-in-situ-hybridization (FISH in 2,445 tumors across 118 different tumor types. Amplification of KCNMA1 was restricted to a small but distinct fraction of breast, ovarian and endometrial cancer with the highest prevalence in invasive ductal breast cancers and serous carcinoma of ovary and endometrium (3-7%. We performed an extensive analysis on breast cancer tissue microarrays (TMA of 1,200 tumors linked to prognosis. KCNMA1 amplification was significantly associated with high tumor stage, high grade, high tumor cell proliferation, and poor prognosis. Immunofluorescence revealed moderate or strong KCNMA1 protein expression in 8 out of 9 human breast cancers and in the breast cancer cell line MFM223. KCNMA1-function in breast cancer cell lines was confirmed by whole-cell patch clamp recordings and proliferation assays, using siRNA-knockdown, BK channel activators such as 17ß-estradiol and the BK-channel blocker paxilline. Our findings revealed that enhanced expression of KCNMA1 correlates with and contributes to high proliferation rate and malignancy of breast cancer.

  10. P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.

    Science.gov (United States)

    Wada, M; Canals, D; Adada, M; Coant, N; Salama, M F; Helke, K L; Arthur, J S; Shroyer, K R; Kitatani, K; Obeid, L M; Hannun, Y A

    2017-11-23

    The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ -/- ) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.

  11. The PIKfyve–ArPIKfyve–Sac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines

    International Nuclear Information System (INIS)

    Ikonomov, Ognian C.; Filios, Catherine; Sbrissa, Diego; Chen, Xuequn; Shisheva, Assia

    2013-01-01

    Highlights: •We assess PAS complex proteins and phosphoinositide levels in breast cancer cells. •Sac3 and ArPIKfyve are markedly elevated in triple-negative breast cancer cells. •Sac3 silencing inhibits proliferation in triple-negative breast cancer cell lines. •Phosphoinositide profiles are altered in breast cancer cells. •This is the first evidence linking high Sac3 with breast cancer cell proliferation. -- Abstract: The phosphoinositide 5-kinase PIKfyve and 5-phosphatase Sac3 are scaffolded by ArPIKfyve in the PIKfyve–ArPIKfyve–Sac3 (PAS) regulatory complex to trigger a unique loop of PtdIns3P–PtdIns(3,5)P 2 synthesis and turnover. Whereas the metabolizing enzymes of the other 3-phosphoinositides have already been implicated in breast cancer, the role of the PAS proteins and the PtdIns3P–PtdIns(3,5)P 2 conversion is unknown. To begin elucidating their roles, in this study we monitored the endogenous levels of the PAS complex proteins in cell lines derived from hormone-receptor positive (MCF7 and T47D) or triple-negative breast cancers (TNBC) (BT20, BT549 and MDA-MB-231) as well as in MCF10A cells derived from non-tumorigenic mastectomy. We report profound upregulation of Sac3 and ArPIKfyve in the triple negative vs. hormone-sensitive breast cancer or non-tumorigenic cells, with BT cell lines showing the highest levels. siRNA-mediated knockdown of Sac3, but not that of PIKfyve, significantly inhibited proliferation of BT20 and BT549 cells. In these cells, knockdown of ArPIKfyve had only a minor effect, consistent with a primary role for Sac3 in TNBC cell proliferation. Intriguingly, steady-state levels of PtdIns(3,5)P 2 in BT20 and T47D cells were similar despite the 6-fold difference in Sac3 levels between these cell lines. However, steady-state levels of PtdIns3P and PtdIns5P, both regulated by the PAS complex, were significantly reduced in BT20 vs. T47D or MCF10A cell lines, consistent with elevated Sac3 affecting directly or indirectly the

  12. Overexpression of YB1 C-terminal domain inhibits proliferation, angiogenesis and tumorigenicity in a SK-BR-3 breast cancer xenograft mouse model.

    Science.gov (United States)

    Shi, Jian-Hong; Cui, Nai-Peng; Wang, Shuo; Zhao, Ming-Zhi; Wang, Bing; Wang, Ya-Nan; Chen, Bao-Ping

    2016-01-01

    Y-box-binding protein 1 (YB1) is a multifunctional transcription factor with vital roles in proliferation, differentiation and apoptosis. In this study, we have examined the role of its C-terminal domain (YB1 CTD) in proliferation, angiogenesis and tumorigenicity in breast cancer. Breast cancer cell line SK-BR-3 was infected with GFP-tagged YB1 CTD adenovirus expression vector. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay showed that YB1 CTD decreased SK-BR-3 cell proliferation, and down-regulated cyclin B1 and up-regulated p21 levels in SK-BR-3 cells. YB1 CTD overexpression changed the cytoskeletal organization and slightly inhibited the migration of SK-BR-3 cells. YB1 CTD also inhibited secreted VEGF expression in SK-BR-3 cells, which decreased SK-BR-3-induced EA.hy926 endothelial cell angiogenesis in vitro. YB1 CTD overexpression attenuated the ability of SK-BR-3 cells to form tumours in nude mice, and decreased in vivo VEGF levels and angiogenesis in the xenografts in SK-BR-3 tumour-bearing mice. Taken together, our findings demonstrate the vital role of YB1 CTD overexpression in inhibiting proliferation, angiogenesis and tumorigenicity of breast cancer cell line SK-BR-3.

  13. Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer.

    Science.gov (United States)

    Jeng, Kuo-Shyang; Jeng, Chi-Juei; Sheen, I-Shyan; Wu, Szu-Hua; Lu, Ssu-Jung; Wang, Chih-Hsuan; Chang, Chiung-Fang

    2018-05-05

    Overexpression of Sonic Hedgehog signaling (Shh) pathway molecules is associated with invasiveness and recurrence in breast carcinoma. Therefore, inhibition of the Shh pathway downstream molecule Glioma-associated Oncogene Homolog (Gli) was investigated for its ability to reduce progression and invasiveness of patient-derived breast cancer cells and cell lines. Human primary breast cancer T2 cells with high expression of Shh signaling pathway molecules were compared with breast cancer line MDA-MB-231 cells. The therapeutic effects of Gli inhibitors were examined in terms of the cell proliferation, apoptosis, cancer stem cells, cell migration and gene expression. Blockade of the Shh signaling pathway could reduce cell proliferation and migration only in MDA-MB-231 cells. Hh pathway inhibitor-1 (HPI-1) increased the percentages of late apoptotic cells in MDA-MB-231 cells and early apoptotic cells in T2 cells. It reduced Bcl2 expression for cell proliferation and increased Bim expression for apoptosis. In addition, Gli inhibitor HPI-1 decreased significantly the percentages of cancer stem cells in T2 cells. HPI-1 worked more effectively than GANT-58 against breast carcinoma cells. In conclusion, HPI-1 could inhibit cell proliferation, reduce cell invasion and decrease cancer stem cell population in breast cancer cells. To target Gli-1 could be a potential strategy to suppress breast cancer stem cells.

  14. Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation

    Science.gov (United States)

    Zhang, Yemin; Zhou, Yu; Li, Mingxin; Wang, Changhua

    2016-01-01

    Previous studies have evidenced that the anticancer potential of curcumin (diferuloylmethane), a main yellow bioactive compound from plant turmeric was mediated by interfering with PI3K/Akt signaling. However, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that curcumin treatment reduced Akt protein expression in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells, along with an activation of autophagy and suppression of ubiquitin-proteasome system (UPS) function. The curcumin-reduced Akt expression, cell proliferation, and migration were prevented by genetic and pharmacological inhibition of autophagy but not by UPS inhibition. Additionally, inactivation of AMPK by its specific inhibitor compound C or by target shRNA-mediated silencing attenuated curcumin-activated autophagy. Thus, these results indicate that curcumin-stimulated AMPK activity induces activation of the autophagy-lysosomal protein degradation pathway leading to Akt degradation and the subsequent suppression of proliferation and migration in breast cancer cell. PMID:26752181

  15. Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells.

    Science.gov (United States)

    Hamdan, Lamia; Arrar, Zoheir; Al Muataz, Yacoub; Suleiman, Lutfi; Négrier, Claude; Mulengi, Joseph Kajima; Boukerche, Habib

    2013-01-01

    This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer.

  16. Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Lamia Hamdan

    Full Text Available This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA, on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231 with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer.

  17. Cyclodextrin-Modified Porous Silicon Nanoparticles for Efficient Sustained Drug Delivery and Proliferation Inhibition of Breast Cancer Cells.

    Science.gov (United States)

    Correia, Alexandra; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Almeida, Sérgio; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2015-10-21

    Over the past decade, the potential of polymeric structures has been investigated to overcome many limitations related to nanosized drug carriers by modulating their toxicity, cellular interactions, stability, and drug-release kinetics. In this study, we have developed a successful nanocomposite consisting of undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with an anticancer drug, sorafenib, and surface-conjugated with heptakis(6-amino-6-deoxy)-β-cyclodextrin (HABCD) to show the impact of the surface polymeric functionalization on the physical and biological properties of the drug-loaded nanoparticles. Cytocompatibility studies showed that the UnTHCPSi-HABCD NPs were not toxic to breast cancer cells. HABCD also enhanced the suspensibility and both the colloidal and plasma stabilities of the UnTHCPSi NPs. UnTHCPSi-HABCD NPs showed a significantly increased interaction with breast cancer cells compared to bare NPs and also sustained the drug release. Furthermore, the sorafenib-loaded UnTHCPSi-HABCD NPs efficiently inhibited cell proliferation of the breast cancer cells.

  18. Downregulated long non-coding RNA MEG3 in breast cancer regulates proliferation, migration and invasion by depending on p53’s transcriptional activity

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Lin [West Biostatistics and Cost-effectiveness Research Center, Medical Insurance Office, West China Hospital of Sichuan University, 610041, Sichuan (China); Li, Yu [Department of Anesthesiology, West China Hospital, Sichuan University, 610041, Sichuan (China); Yang, Bangxiang, E-mail: b19933009@qq.coom [Department of Pain Management, West China Hospital of Sichuan University, 610041, Sichuan (China)

    2016-09-09

    Long non-coding RNAs (lncRNAs) was found to play critical roles in tumorigenesis, hence, screen of tumor-related lncRNAs, identification of their biological roles is important for understanding the processes of tumorigenesis. In this study, we identified the expressing difference of several tumor-related lncRNAs in breast cancer samples and found that, MEG3, which is downregulated in non-small cell lung cancer (NSCLC) tumor tissues, is also downregulated in breast cancer samples compared with adjacent tissues. For figuring out the effect of MEG3 in breast cancer cells MCF7 and MB231, we overexpressed MEG3 in these cells, and found that it resulted the inhibition of proliferation, colony formation, migration and invasion capacities by enhancing p53’s transcriptional activity on its target genes, including p21, Maspin and KAI1. MEG3 presented similar effects in MB157, which is a p53-null breast cancer cell line, when functional p53 but not p53R273H mutant, which lacks transcriptional activity, was introduced. Surprisingly, overexpression of MEG3 activates p53’s transcriptional activity by decreasing MDM2’s transcription level, and thus stabilizes and accumulates P53. Taken together, our findings indicate that MEG3 is downregulated in breast cancer tissues and affects breast cancer cells’ malignant behaviors, which indicate MEG3 a potential therapeutic target for breast cancer. - Highlights: • MEG3 RNA is widely downregulated in breast tumor tissue. • MEG3 regulates P53 indirectly through transcriptional regulation of MDM2. • Under unstressed condition, MEG3-related P53 accumulation transcriptionally activates p53’s target genes. • MEG3 expression level tightly regulates proliferation, colony formation, migration and invasion in breast tumor cells.

  19. INHIBITION OF SPONTANEOUS APOPTOSIS IN HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    邵志敏; 江明; 吴炅; 余黎民; 韩企夏; 张延璆; 沈镇宙

    1996-01-01

    Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptcsis,a genetically prograined process of autonomous ceil death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer sampies. We found there is a great inhibition of spontaneous apoptosis in breast cancer ceils compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

  20. The Use of Novel PET Tracers to Image Breast Cancer Biologic Processes Such as Proliferation, DNA Damage and Repair, and Angiogenesis.

    Science.gov (United States)

    Kenny, Laura

    2016-02-01

    The balance between proliferation and cell death is pivotal to breast tumor growth. Because of a combination of environmental and genetic factors leading to activation of oncogenes or inactivation of tumor suppressor genes, these processes become deregulated in cancer. PET imaging of proliferation, angiogenesis, and DNA damage and repair offers the opportunity to monitor therapeutic efficacy to detect changes in tumor biology that may precede physical size reduction and simultaneously allows the study of intratumoral and intertumoral heterogeneity.This review examines recent developments in breast cancer imaging using novel probes. The probes discussed here are not licensed for routine use and are at various stages of development ranging from preclinical development (e.g., the DNA repair marker γH2AX) to clinical validation in larger studies (such as the proliferation probe 3'-deoxy-3'-(18)F-fluorothymidine [(18)F-FLT]). In breast cancer, most studies have focused on proliferation imaging mainly based on (18)F-labeled thymidine analogs. Initial studies have been promising; however, the results of larger validation studies are necessary before being incorporated into routine clinical use. Although there are distinct advantages in using process-specific probes, properties such as metabolism need careful consideration, because high background uptake in the liver due to glucuronidation in the case of (18)F-FLT may limit utility for imaging of liver metastases.Targeting angiogenesis has had some success in tumors such as renal cell carcinoma; however, angiogenesis inhibitors have not been particularly successful in the clinical treatment of breast cancer. This could be potentially attributed to patient selection due to the lack of validated predictive and responsive biomarkers; the quest for a successful noninvasive biomarker for angiogenesis could solve this challenge. Finally, we look at cell death including apoptosis and DNA damage and repair probes, the most well

  1. Interleukin-19 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2013-01-01

    Full Text Available Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL- 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored both in vitro and in vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

  2. Increased utilization of fructose has a positive effect on the development of breast cancer

    Directory of Open Access Journals (Sweden)

    Xiajing Fan

    2017-09-01

    Full Text Available Rapid proliferation and Warburg effect make cancer cells consume plenty of glucose, which induces a low glucose micro-environment within the tumor. Up to date, how cancer cells keep proliferating in the condition of glucose insufficiency still remains to be explored. Recent studies have revealed a close correlation between excessive fructose consumption and breast cancer genesis and progression, but there is no convincing evidence showing that fructose could directly promote breast cancer development. Herein, we found that fructose, not amino acids, could functionally replace glucose to support proliferation of breast cancer cells. Fructose endowed breast cancer cells with the colony formation ability and migratory capacity as effective as glucose. Interestingly, although fructose was readily used by breast cancer cells, it failed to restore proliferation of non-tumor cells in the absence of glucose. These results suggest that fructose could be relatively selectively employed by breast cancer cells. Indeed, we observed that a main transporter of fructose, GLUT5, was highly expressed in breast cancer cells and tumor tissues but not in their normal counterparts. Furthermore, we demonstrated that the fructose diet promoted metastasis of 4T1 cells in the mouse models. Taken together, our data show that fructose can be used by breast cancer cells specifically in glucose-deficiency, and suggest that the high-fructose diet could accelerate the progress of breast cancer in vivo.

  3. Selective anti-proliferation of HER2-positive breast cancer cells by anthocyanins identified by high-throughput screening.

    Directory of Open Access Journals (Sweden)

    Weihua Liu

    Full Text Available Overexpressed Human epidermal growth factor receptor 2 (HER2 drives the biology of 20% breast cancer and is a prediction of a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients. Traditional Chinese herbs/medicines have been used to treat breast cancer patients including HER2-positive patients in Asia for decades. Although the traditional medicines demonstrate efficacy in clinics for HER2-positive patients, the mechanism is largely unknown. In this article, we screened a 10,000 natural product library in 6 different cell lines representing breast cancer, and assessed the ability of each drug to cause cytotoxicity through a high-throughput screening approach. We have identified eight natural compounds that selectively inhibit the proliferation of HER2-positive cells. Two of the hit compounds, peonidin-3-glucoside and cyaniding-3-glucoside, are both extracts from black rice. They inhibit the phospho-HER2 and phospho-AKT and were confirmed to induce HER2-psotive breast cancer cells apoptosis both in vitro and in vivo. Peonidin-3-glucoside and cyaniding-3-glucoside treatments significantly reduced the tumor size and volume in vivo compared to the control group. There is no significant difference of antitumorgenic effects between peonidin-3-glucoside and cyaniding-3-glucoside treatments.

  4. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

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    L. Zhao

    2014-01-01

    Full Text Available Fanconi anemia complementation group F protein (FANCF is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  5. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    International Nuclear Information System (INIS)

    Zhao, L.; Li, N.; Yu, J.K.; Tang, H.T.; Li, Y.L.; He, M.; Yu, Z.J.; Bai, X.F.; Zheng, Z.H.; Wang, E.H.; Wei, M.J.

    2013-01-01

    Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer

  6. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.; Li, N.; Yu, J.K.; Tang, H.T.; Li, Y.L.; He, M.; Yu, Z.J.; Bai, X.F. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Zheng, Z.H.; Wang, E.H. [Institute of Pathology and Pathophysiology, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Wei, M.J. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China)

    2013-12-12

    Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  7. BMP9 inhibits proliferation and metastasis of HER2-positive SK-BR-3 breast cancer cells through ERK1/2 and PI3K/AKT pathways.

    Science.gov (United States)

    Ren, Wei; Liu, Yuehong; Wan, Shaoheng; Fei, Chang; Wang, Wei; Chen, Yingying; Zhang, Zhihui; Wang, Ting; Wang, Jinshu; Zhou, Lan; Weng, Yaguang; He, Tongchuan; Zhang, Yan

    2014-01-01

    Bone morphogenetic protein 9 (BMP9), a member of TGF-β superfamily, is reported to inhibit the growth and migration of prostate cancer, osteosarcoma and triple-negative MDA-MB-231 breast cancer cells. However, little is known about the effect of on the biological behaviors of HER2-positive SK-BR-3 breast cancer cells and the underlying mechanisms. This study aimed to investigate the effects of BMP9 on the proliferation and metastasis of SK-BR-3 cells with BMP9 over-expression or BMP9 down-regulated expression. Results indicated that exogenously expressed BMP9 inhibited the proliferation and metastasis of SK-BR-3 cells while decreased endogenous BMP9 expression in SK-BR-3 cells promoted the proliferation and migration of breast cancer cells in vitro and in vivo. In SK-BR-3 cells with BMP9 over-expression, the phosphorylation of HER2, ERK1/2 and AKT was markedly suppressed and the HER2 expression decreased at both mRNA and protein levels, while opposite results were observed in SK-BR-3 cells with BMP9 knock down. When the phosphorylation of ERK1/2 and PI3K/AKT was inhibited by PD98059 and LY294002, respectively, the decreased proliferation and invasion induced by BMP9 knock down were eliminated. These findings suggest that BMP9 can inhibit the proliferation and metastasis of SK-BR-3 cells via inactivating ERK1/2 and PI3K/AKT signaling pathways. Thus, BMP9 may serve as a useful agent in the treatment of HER-2 positive breast cancer.

  8. PKCα expression is a marker for breast cancer aggressiveness

    Directory of Open Access Journals (Sweden)

    Jirström Karin

    2010-04-01

    Full Text Available Abstract Background Protein kinase C (PKC isoforms are potential targets for breast cancer therapy. This study was designed to evaluate which PKC isoforms might be optimal targets for different breast cancer subtypes. Results In two cohorts of primary breast cancers, PKCα levels correlated to estrogen and progesterone receptor negativity, tumor grade, and proliferative activity, whereas PKCδ and PKCε did not correlate to clinicopathological parameters. Patients with PKCα-positive tumors showed poorer survival than patients with PKCα-negative tumors independently of other factors. Cell line studies demonstrated that PKCα levels are high in MDA-MB-231 and absent in T47D cells which proliferated slower than other cell lines. Furthermore, PKCα silencing reduced proliferation of MDA-MB-231 cells. PKCα inhibition or downregulation also reduced cell migration in vitro. Conclusions PKCα is a marker for poor prognosis of breast cancer and correlates to and is important for cell functions associated with breast cancer progression.

  9. MicroRNA-101 inhibits cell proliferation, promotes cell apoptosis and increases sensitivity of breast cancer MDA-MB-231 cells to paclitaxel

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    Qiu-Lin Ke

    2016-02-01

    Full Text Available Objective: To explore the effect that miR-101 inhibits breast cancer MDA-MB-231 cell proliferation and increases the chemosensitivity of paclitaxel to breast cancer MDA-MB-231 cells and its influence on protein expression level of target gene Bcl2. Methods: miR-101 was artificially synthesized, it used liposome 3000 to transfect MDA-MB-231 cells, and experiment was divided into three groups: blank control group, negative control group and miR-101 group. MTT assay was used to detect the effect of miR-101 on MDA-MB-231 cell proliferation and chemosensitivity of paclitaxel-mediated MDA-MB-231 cells; flow cytometer was used to detect cell apoptosis. Real-time PCR and Western bloting were used to detect the changes of mRNA and protein expression levels of Bcl2. Results: After miR-101 transfected MDA-MB- 231 cells, cell proliferation ability significantly decreased compared with negative control group, and differences had statistical significance (P<0.01; after paclitaxel was used to process cells, IC50 of miR-101-processing group decreased by 2.45 times compared with blank control group, differences had statistical significance (P<0.05 and differences between blank control group and negative control group had no statistical significance; detection results by flow cytometer showed that both early-stage and late-stage apoptosis rates of MDA-MB-231 cells of miR-101 group were significantly higher than those of negative control group (P<0.05, and early-stage apoptosis rate was more significant (P<0.01; after transfection of miR-101, mRNA and protein levels of Bcl2 of MDA-MB-231 cells significantly decreased, and differences had statistical significance (P<0.05. Conclusion: miR-101 can inhibit breast cancer MDAMB- 231 cell proliferation through targeting and downregulating Bcl2, thereby increasing the chemosensitivity of breast cancer cells to paclitaxel and promoting cell apoptosis.

  10. FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tian-Li [Department of General Surgery, The People’s Hospital of Wuqing, Tianjin (China); Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Yue [Department of Respiration, Affiliated Hospital of Medical College of Chinese People’s Armed Police Force, Tianjin (China); Chen, Ao-Xiang; Sun, Xuan [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie, E-mail: gejie198003@163.com [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2014-04-04

    Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy.

  11. FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

    International Nuclear Information System (INIS)

    Chu, Tian-Li; Zhao, Hong-Meng; Li, Yue; Chen, Ao-Xiang; Sun, Xuan; Ge, Jie

    2014-01-01

    Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy

  12. Polymorphisms in steroid hormone biosynthesis genes and risk of breast cancer and fibrocystic breast conditions in Chinese women.

    Science.gov (United States)

    Sakoda, Lori C; Blackston, Christie; Doherty, Jennifer A; Ray, Roberta M; Lin, Ming Gang; Stalsberg, Helge; Gao, Dao Li; Feng, Ziding; Thomas, David B; Chen, Chu

    2008-05-01

    Common variants in genes encoding for key enzymes involved in steroidogenesis may alter sex steroid hormone levels, thereby influencing susceptibility to breast carcinoma and related conditions. In a case-control study of Chinese women, we examined genotypes of the CYP11A1 pentanucleotide [(TAAAA)n] repeat (D15S520), CYP17A1 rs743572, and HSD17B1 rs605059 polymorphisms in relation to the risk of breast cancer and fibrocystic breast conditions, comparing 615 women with breast cancer and 467 women with fibrocystic breast conditions separately with 879 women without clinical breast disease. We also evaluated whether these relationships differed by the presence of proliferation in the extratumoral epithelium or fibrocystic lesions, menopausal status, or body mass index. Only CYP11A1 genotype was related to breast cancer risk, with women homozygous for the 4-repeat allele, relative to those homozygous for the 6-repeat allele, at reduced risk (age-adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.91). There was some suggestion of a stronger inverse association for breast cancer with evidence of proliferation in the extratumoral epithelium than for breast cancer without extratumoral proliferation. Breast cancer risk associated with CYP11A1 genotype did not differ by menopausal status or body mass index level. No associations between CYP11A1, CYP17A1, and HSD17B1 genotypes and risk of fibrocystic breast conditions were observed. Our findings support the possibility that common allelic variation at the CYP11A1 D15S520 locus alters breast cancer risk in Chinese women.

  13. Cadmium promotes the proliferation of triple-negative breast cancer cells through EGFR-mediated cell cycle regulation

    International Nuclear Information System (INIS)

    Wei, Zhengxi; Song, Xiulong; Shaikh, Zahir A.

    2015-01-01

    Cadmium (Cd) is a carcinogenic metal which is implicated in breast cancer by epidemiological studies. It is reported to promote breast cancer cell growth in vitro through membrane receptors. The study described here examined Cd-mediated growth of non-metastatic human breast cancer derived cells that lack receptors for estrogen, progesterone, and HER2. Treatment of triple-negative HCC 1937 cells with 0.1–0.5 μM Cd increased cell growth by activation of AKT and ERK. Accelerated cell cycle progression was achieved by increasing the levels of cyclins A, B, and E, as well as those of CDKs 1 and 2. Although triple negative cells lack estrogen receptor, they express high levels of EGFR. Therefore, further studies on HCC 1937 and another triple-negative cell line, HCC 38, were conducted using specific siRNA and an inhibitor of EGFR to determine whether EGFR was responsible for mediating the effect of Cd. The results revealed that in both cell types EGFR was not only activated upon Cd treatment, but was also essential for the downstream activation of AKT and ERK. Based on these observations, it is concluded that, in breast cancer cells lacking estrogen receptor, sub-micromolar concentration of Cd can promote cell proliferation. Furthermore, that EGFR plays a critical role in this process. - Highlights: • Sub-micromolar concentrations of Cd promote cell growth in breast cancer cells that lack ER, PR, and HER2. • The increase in cell number is not due to reduction in apoptosis. • Growth promotion involves AKT and ERK signaling and downstream stimulation of cell cycle progression. • Initiation of cell growth by Cd occurs at the cell membrane and requires the activation of EGFR.

  14. Breast fibroblasts modulate epithelial cell proliferation in three-dimensional in vitro co-culture

    International Nuclear Information System (INIS)

    Sadlonova, Andrea; Novak, Zdenek; Johnson, Martin R; Bowe, Damon B; Gault, Sandra R; Page, Grier P; Thottassery, Jaideep V; Welch, Danny R; Frost, Andra R

    2005-01-01

    Stromal fibroblasts associated with in situ and invasive breast carcinoma differ phenotypically from fibroblasts associated with normal breast epithelium, and these alterations in carcinoma-associated fibroblasts (CAF) may promote breast carcinogenesis and cancer progression. A better understanding of the changes that occur in fibroblasts during carcinogenesis and their influence on epithelial cell growth and behavior could lead to novel strategies for the prevention and treatment of breast cancer. To this end, the effect of CAF and normal breast-associated fibroblasts (NAF) on the growth of epithelial cells representative of pre-neoplastic breast disease was assessed. NAF and CAF were grown with the nontumorigenic MCF10A epithelial cells and their more transformed, tumorigenic derivative, MCF10AT cells, in direct three-dimensional co-cultures on basement membrane material. The proliferation and apoptosis of MCF10A cells and MCF10AT cells were assessed by 5-bromo-2'-deoxyuridine labeling and TUNEL assay, respectively. Additionally, NAF and CAF were compared for expression of insulin-like growth factor II as a potential mediator of their effects on epithelial cell growth, by ELISA and by quantitative, real-time PCR. In relatively low numbers, both NAF and CAF suppressed proliferation of MCF10A cells. However, only NAF and not CAF significantly inhibited proliferation of the more transformed MCF10AT cells. The degree of growth inhibition varied among NAF or CAF from different individuals. In greater numbers, NAF and CAF have less inhibitory effect on epithelial cell growth. The rate of epithelial cell apoptosis was not affected by NAF or CAF. Mean insulin-like growth factor II levels were not significantly different in NAF versus CAF and did not correlate with the fibroblast effect on epithelial cell proliferation. Both NAF and CAF have the ability to inhibit the growth of pre-cancerous breast epithelial cells. NAF have greater inhibitory capacity than CAF

  15. Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo

    Directory of Open Access Journals (Sweden)

    Dong Y

    2017-12-01

    Full Text Available Yan Dong,1,* Cai Chang,2,* Jingtian Liu,3 Jinwei Qiang4 1Department of Ultrasonography, Jinshan Hospital, 2Department of Ultrasonography, Cancer Center, 3Department of General Surgery, 4Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China *These authors contributed equally to this work Abstract: Breast cancer remains a major cause of cancer-related death in women worldwide. Dysregulation of microRNAs (miRNAs is involved in the initiation and progression of breast cancer. Moreover, it was found that GIT1 was widely involved in the development of many human cancers. Herein, we aimed to investigate the expression changes of miR-149* and GIT1 and the functional effects of miR-149*/GIT1 link in breast cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR and Western blot (WB were used to examine the expression levels of miR-149* and GIT1. Dual luciferase reporter assay was utilized to confirm the target interaction between miR-149* and GIT1. The biological functions, including cell proliferation, invasion, and migration, of miR-149* and GIT1 were determined by MTT assay and Transwell assays, respectively. Eventually, the tumor xenograft model in nude mice injected with stable transfected MDA-MB-231 cells was established to verify the effects of miR-149* and GIT1 on tumor growth. Our results showed that miR-149* expression was decreased, whereas GIT1 expression was increased in clinical samples of breast cancer. Based on the inverse expression trend between miR-149* and GIT1, we further demonstrated that miR-149* indeed directly targets GIT1. Subsequently, it was observed that inhibition of miR-149* significantly promoted cell proliferation, invasion, and migration, but the ability of cell proliferation, invasion, and migration was obviously declined after silencing of GIT1 in MDA-MB-231 cells transfected with miR-149* mimic and/or si-GIT1. Finally, it was also found that elevated miR-149* decelerated

  16. Effects of hydroxyapatite nanoparticles on proliferation and apoptosis of human breast cancer cells (MCF-7)

    International Nuclear Information System (INIS)

    Meena, Ramovatar; Kesari, Kavindra Kumar; Rani, Madhu; Paulraj, R.

    2012-01-01

    The study aimed to correlate cell proliferation inhibition with oxidative stress and p53 protein expression in cancerous cells. Hydroxyapatite (HAP) (Ca 10 (PO 4 ) 6 (OH) 2 ) is the essential component of inorganic composition in human bone. It has been found to have obvious inhibitory function on growth of many kinds of tumor cells and its nanoparticle has stronger anti-cancerous effect than macromolecule microparticles. Human breast cancer cells (MCF-7) were cultured and treated with HAP nanoparticles at various concentrations. Cells viability was detected with MTT colorimetric assay. The morphology of the cancerous cells was performed by transmission electron microscopy and the expression of a cell apoptosis related gene (p53) was determined by ELISA assay and flow cytometry (FCM). The intracellular reactive oxygen species (ROS) level in HAP exposed cells was measured by H 2 DCFDA staining. DNA damage was measured by single-cell gel electrophoresis assay. The statistical analysis was done by one way ANOVA. The cellular proliferation inhibition rate was significantly (p < 0.05) increasing in a dose-dependent manner of HAP nanoparticles. Cell apoptotic characters were observed after MCF-7 cells were treated by HAP nanoparticles for 48 h. Moreover, ELISA assay and FCM shows a dose-dependent activation of p53 in MCF-7 cells treated with nanoHAP. These causative factors of the above results may be justified by an overproduction of ROS. In this study, a significant (p < 0.05) increase in the level of intracellular ROS in HAP-treated cells was observed. This study shows that HAP inhibits the growth of human breast cancer MCF-7 cells as well as induces cell apoptosis. This study shows that HAP NPs Induce the production of intracellular reactive oxygen species and activate p53, which may be responsible for DNA damage and cell apoptosis.

  17. Adipocyte activation of cancer stem cell signaling in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

    Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

  18. Downregulation of the long non-coding RNA TUG1 is associated with cell proliferation, migration, and invasion in breast cancer.

    Science.gov (United States)

    Fan, Shulin; Yang, Zhaoying; Ke, Zirui; Huang, Keke; Liu, Ning; Fang, Xuedong; Wang, Keren

    2017-11-01

    Recent studies have identified many long non-coding RNAs (lncRNAs) with critical roles in various biological processes including tumorigenesis. Taurine-upregulated gene 1 (TUG1), is an lncRNA recently reported to be involved in the progression of several human cancers. This study aimed to investigate the clinical significance and biological functions of TUG1 in breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure TUG1 expression in cells from breast cancer cell lines and in 58 matched pairs of breast cancer and normal tissue samples from patients with clinicopathological comparisons. Gain-and loss-of-function experiments were performed in vitro to investigate the biological role of TUG1. TUG1 expression was significantly downregulated in both breast cancer tissues and cell lines compared to controls, and low TUG1 expression was significantly correlated with mutant p53 expression (p=0.037) and lymph node metastasis (p=0.044). In vitro experiments revealed that TUG1 overexpression significantly suppressed cell proliferation by causing cell cycle arrest and inducing apoptosis in breast cancer cells, while TUG1 knockdown caused increased cell growth via promoting cell cycle progression and regulating the expression of cyclinD1 and CDK4. Further functional assays indicated that TUG1 overexpression significantly promoted cell migration and invasion while TUG1 knockdown had the opposite effects. Our findings indicate that the lncRNA TUG1 is a tumor suppressor in breast cancer, and may serve as a novel prognostic biomarker and potential therapeutic target for patients with breast cancer. Copyright © 2017. Published by Elsevier Masson SAS.

  19. Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes

    Directory of Open Access Journals (Sweden)

    Yao Wei

    2016-06-01

    Full Text Available Shikonin is a naphthoquinone isolated from the traditional Chinese medicine Lithospermum. It has been used in the treatment of various tumors. However, the effects of shikonin on such diseases have not been fully elucidated. In the present study, we detected the exosome release of a breast cancer cell line (MCF-7 with shikonin treatment and found a positive relationship between the level of secreted exosomes and cell proliferation. We next analyzed miRNA profiles in MCF-7 cells and exosomes and found that some miRNAs are specifically sorted and abundant in exosomes. Knockdown of the most abundant miRNAs in exosomes and the MCF-7 proliferation assay showed that miR-128 in exosomes negatively regulates the level of Bax in MCF-7 recipient cells and inhibits cell proliferation. These results show that shikonin inhibits the proliferation of MCF-7 cells through reducing tumor-derived exosomal miR-128. The current study suggests that shikonin suppresses MCF-7 growth by the inhibition of exosome release.

  20. Tumor-suppressor activity of RRIG1 in breast cancer

    International Nuclear Information System (INIS)

    Zhang, Guihong; Brewster, Abenaa; Guan, Baoxiang; Fan, Zhen; Brown, Powel H; Xu, Xiao-Chun

    2011-01-01

    Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion. Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity. The immunohistochemical data showed that RRIG1 expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. RRIG1 expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of RRIG1 expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential. The data from the current study indicated that RRIG1 expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer

  1. Mevalonates, Ras and Breast Cancer

    National Research Council Canada - National Science Library

    White, Michael

    2001-01-01

    .... This selective inhibition appears to be a consequence of expression of oncogenic Ras. Here we are evaluating the ability of Fmev to selectively interfere with proliferation of breast cancer cells...

  2. Mechanisms of dihydrotestosterone action on resveratrol-induced anti-proliferation in breast cancer cells with different ERα status.

    Science.gov (United States)

    Chin, Yu-Tang; Yang, Sheng-Huei; Chang, Tung-Cheng; Changou, Chun A; Lai, Hsuan-Yu; Fu, Earl; HuangFu, Wei-Chun; Davis, Paul J; Lin, Hung-Yun; Liu, Leroy F

    2015-11-03

    Dihydrotestosterone (DHT) has been shown to promote breast cancer growth via different mechanisms. In addition to binding to ERα, the DHT membrane receptor exists on integrin αvβ3. Resveratrol induces p53-dependent apoptosis via plasma membrane integrin αvβ3. Resveratrol and DHT signals are both transduced by activated ERK1/2; however, DHT promotes cell proliferation in cancer cells, whereas resveratrol is pro-apoptotic. In this study, we examined the mechanism by which DHT inhibits resveratrol-induced apoptosis in human ERα positive (MCF-7) and negative (MDA-MB-231) breast cancer cells. DHT inhibited resveratrol-stimulated phosphorylation of Ser-15 of p53 in a concentration-dependent manner. These effects of DHT on resveratrol action were blocked by an ERα antagonist, ICI 182,780, in MCF-7 breast cancer cells. DHT inhibited resveratrol-induced nuclear complex of p53-COX-2 formation which is required p53-dependent apoptosis. ChIP studies of COX-2/p53 binding to DNA and expression of p53-responsive genes indicated that DHT inhibited resveratrol-induced p53-directed transcriptional activity. In addition, DHT did inhibit resveratrol-induced COX-2/p53-dependent gene expression. These results suggest that DHT inhibits p53-dependent apoptosis in breast cancer cells by interfering with nuclear COX-2 accumulation which is essential for stimulation of apoptotic pathways. Thus, the surface receptor sites for resveratrol and DHT are discrete and activate ERK1/2-dependent downstream effects on apoptosis that are distinctive. These studies provide new insights into the antagonizing effects of resveratrol versus DHT, an important step toward better understanding and eventually treating breast cancer. It also indicates the complex pathways by which apoptosis is induced by resveratrol in DHT-depleted and -repleted environments.

  3. Protein tyrosine phosphatase µ (PTP µ or PTPRM, a negative regulator of proliferation and invasion of breast cancer cells, is associated with disease prognosis.

    Directory of Open Access Journals (Sweden)

    Ping-Hui Sun

    Full Text Available BACKGROUND: PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells. DESIGN: Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models. RESULTS: A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK. CONCLUSIONS: Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.

  4. Silencing of the HER2/neu Gene by siRNA Inhibits Proliferation and Induces Apoptosis in HER2/neu-Overexpressing Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Timo Faltus

    2004-11-01

    Full Text Available In eukaryotes, double-stranded (ds RNA induces sequence-specific inhibition of gene expression referred to as RNA interference (RNAi. We exploited RNAi to define the role of HER2/neu in the neoplastic proliferation of human breast cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer cells with short interfering RNA (siRNA targeted against human HER2/neu and analyzed the specific inhibition of HER2/neu expression by Northern and Western blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific decrease in HER2/neu mRNA and protein levels. Moreover, transfection with HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines SKBR-3 and BT-474, consistent with a powerful RNA silencing effect. siRNA treatment resulted in an antiproliferative and apoptotic response in cells overexpressing HER2/neu, but had no influence in cells with almost no expression of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu function is essential for the proliferation of HER2/neuoverexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as anti proliferative agents that display activity against neoplastic cells at very low doses.

  5. Melatonin, Aging and Breast Cancer

    National Research Council Canada - National Science Library

    Hill, Steven

    2001-01-01

    ... conditions for tumor induction, promotion and progression. The pineal gland, via its hormone melatonin, has been shown by numerous laboratories to inhibit the proliferation of both human and animal models of breast cancer...

  6. Olive phenolics as c-Met inhibitors: (--Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

    Directory of Open Access Journals (Sweden)

    Mohamed R Akl

    Full Text Available Dysregulation of the Hepatocyte growth factor (HGF/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT, angiogenesis, invasion, and metastasis. (--Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (--oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (--oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (--oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (--oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (--oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (--oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.

  7. The role of intratumoral and systemic IL-6 in breast cancer

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Højfeldt, Grith Westergaard; Hojman, Pernille

    2013-01-01

    review the associations between IL-6 and breast cancer ranging from in vitro cell culture studies to clinical studies, covering the role of IL-6 in controlling breast cancer cell growth, regulation of cancer stem cell renewal, as well as breast cancer cell migration. Moreover, associations between...... is important for controlling breast cancer cell growth, metastasis, and self renewal of cancer stem cells....... circulating IL-6 and risk of breast cancer, prognosis for patients with prevalent disease, adverse effects and interventions to control systemic IL-6 levels in patients are discussed. In summary, direct application of IL-6 on breast cancer cells inhibits proliferation in estrogen receptor positive cells...

  8. BP1 Homeoprotein Enhances Metastatic Potential in ER-negative Breast Cancer

    Science.gov (United States)

    Fu, Yebo; Lian, Yi; Kim, Kyung Soon; Zhang, Lei; Hindle, A. Katharine; Brody, Fred; Siegel, Robert S.; McCaffrey, Timothy A.; Fu, Sidney W.

    2010-01-01

    Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. It was reported that BP1, a homeobox isoform of DLX4, is overexpressed in 80% of breast cancer patients and in 100% of estrogen receptor negative (ER-) tumors. The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and tumorigenesis. These findings imply that BP1 may play an important role in ER- breast cancer. We sought to determine the effects and mechanisms of BP1 on cell proliferation and metastasis using ER- Hs578T cells as a model. Cells were transfected with either pcDNA3.2 plasmid containing BP1 gene, or pcDNA3.2 vector, then selected and cloned. Overexpression of BP1 increased cell proliferation rate by 2-5 fold (p=2.0. Of those genes, 49 were up-regulated and 22 were down-regulated. Significant pathways were identified involving cell proliferation and metastasis. These data demonstrated that overexpression of BP1 significantly enhanced cell proliferation and metastatic potential in ER- Hs578T cells. Further analysis with more ER- cell lines and patient samples is warranted to establish BP1 as a therapeutic target for ER- breast cancer. PMID:20842225

  9. The Fbw7 tumor suppressor targets KLF5 for ubiquitin-mediated degradation and suppresses breast cell proliferation.

    Science.gov (United States)

    Zhao, Dong; Zheng, Han-Qiu; Zhou, Zhongmei; Chen, Ceshi

    2010-06-01

    Fbw7 is a tumor suppressor frequently inactivated in cancers. The KLF5 transcription factor promotes breast cell proliferation and tumorigenesis through upregulating FGF-BP. The KLF5 protein degrades rapidly through the ubiquitin proteasome pathway. Here, we show that the Skp1-CUL1-Fbw7 E3 ubiquitin ligase complex (SCF(Fbw7)) targets KLF5 for ubiquitin-mediated degradation in a GSK3beta-mediated KLF5 phosphorylation-dependent manner. Mutation of the critical S303 residue in the KLF5 Cdc4 phospho-degrons motif ((303)SPPSS) abolishes the protein interaction, ubiquitination, and degradation by Fbw7. Inactivation of endogenous Fbw7 remarkably increases the endogenous KLF5 protein abundances. Endogenous Fbw7 suppresses the FGF-BP gene expression and breast cell proliferation through targeting KLF5 for degradation. These findings suggest that Fbw7 inhibits breast cell proliferation at least partially through targeting KLF5 for proteolysis. This new regulatory mechanism of KLF5 degradation may result in useful diagnostic and therapeutic targets for breast cancer and other cancers. Copyright 2010 AACR.

  10. Cullin1 is a novel marker of poor prognosis and a potential therapeutic target in human breast cancer.

    Science.gov (United States)

    Bai, J; Yong, H M; Chen, F F; Mei, P J; Liu, H; Li, C; Pan, Z Q; Wu, Y P; Zheng, J N

    2013-08-01

    To investigate the role of Cullin1 (Cul1) in the development of breast cancer, we examined the expression of Cul1 in breast cancer tissues and analyzed the correlation between Cul1 expression and clinicopathologic variables and patients survival. We evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) which includes 393 breast cancer tissues. We also studied the role of Cul1 in breast cancer cell proliferation, migration and invasion by carrying out CCK8 cell proliferation assay, cell migration and invasion assay. The Cul1 expression was significantly correlated with breast cancer histology grade (P = 0.000), estrogen receptor status (P = 0.001), progesterone receptor status (P = 0.001) and human epidermal growth factor receptor 2 status (P = 0.002). Furthermore, we showed a strong correlation between high Cul1 expression and worse 5-year overall and disease-specific survival rates in breast cancer patients (P = 0.026 and P = 0.015, respectively). Finally, we found that Cul1 knockdown inhibits cell proliferation, migration and invasion abilities. Cul1 overexpression is significantly correlated with breast cancer progression and predicts worse survival. Cul1 regulates breast cancer cell proliferation, migration and invasion.

  11. An Advanced Deep Learning Approach for Ki-67 Stained Hotspot Detection and Proliferation Rate Scoring for Prognostic Evaluation of Breast Cancer.

    Science.gov (United States)

    Saha, Monjoy; Chakraborty, Chandan; Arun, Indu; Ahmed, Rosina; Chatterjee, Sanjoy

    2017-06-12

    Being a non-histone protein, Ki-67 is one of the essential biomarkers for the immunohistochemical assessment of proliferation rate in breast cancer screening and grading. The Ki-67 signature is always sensitive to radiotherapy and chemotherapy. Due to random morphological, color and intensity variations of cell nuclei (immunopositive and immunonegative), manual/subjective assessment of Ki-67 scoring is error-prone and time-consuming. Hence, several machine learning approaches have been reported; nevertheless, none of them had worked on deep learning based hotspots detection and proliferation scoring. In this article, we suggest an advanced deep learning model for computerized recognition of candidate hotspots and subsequent proliferation rate scoring by quantifying Ki-67 appearance in breast cancer immunohistochemical images. Unlike existing Ki-67 scoring techniques, our methodology uses Gamma mixture model (GMM) with Expectation-Maximization for seed point detection and patch selection and deep learning, comprises with decision layer, for hotspots detection and proliferation scoring. Experimental results provide 93% precision, 0.88% recall and 0.91% F-score value. The model performance has also been compared with the pathologists' manual annotations and recently published articles. In future, the proposed deep learning framework will be highly reliable and beneficial to the junior and senior pathologists for fast and efficient Ki-67 scoring.

  12. Mesenchymal stem cells expressing interleukin-18 inhibit breast cancer in a mouse model.

    Science.gov (United States)

    Liu, Xiaoyi; Hu, Jianxia; Li, Yueyun; Cao, Weihong; Wang, Yu; Ma, Zhongliang; Li, Funian

    2018-05-01

    Development of an improved breast cancer therapy has been an elusive goal of cancer gene therapy for a long period of time. Human mesenchymal stem cells derived from umbilical cord (hUMSCs) genetically modified with the interleukin (IL)-18 gene (hUMSCs/IL-18) were previously demonstrated to be able to suppress the proliferation, migration and invasion of breast cancer cells in vitro . In the present study, the effect of hUMSCs/IL-18 on breast cancer in a mouse model was investigated. A total of 128 mice were divided into 2 studies (the early-effect study and the late-effect study), with 4 groups in each, including the PBS-, hUMSC-, hUMSC/vector- and hUMSC/IL-18-treated groups. All treatments were injected along with 200 µl PBS. Following therapy, the tumor size, histological examination, and expression of lymphocytes, Ki-67, cluster of differentiation 31 and cytokines [interleukin (IL)-18, IL-12, interferon (IFN)-γ and TNF-α] in each group were analyzed. Proliferation of cells (assessed by measuring tumor size and Ki-67 expression) and metastasis, (by determining pulmonary and hepatic metastasis) of breast cancer cells in the hUMSC/IL-18 group were significantly decreased compared with all other groups. hUMSCs/IL-18 suppressed tumor cell proliferation by activating immunocytes and immune cytokines, decreasing the proliferation index of proliferation marker protein Ki-67 of tumor cells and inhibiting tumor angiogenesis. Furthermore, hUMSCs/IL-18 were able to induce a more marked and improved therapeutic effect in the tumor sites, particularly in early tumors. The results of the present study indicate that hUMSCs/IL-18 were able to inhibit the proliferation and metastasis of breast cancer cells in vivo , possibly leading to an approach for a novel antitumor therapy in breast cancer.

  13. Leptin: A proliferative factor for breast cancer?

    International Nuclear Information System (INIS)

    Caldefie-Chezet, F.; Damez, M.; Latour, M. de; Konska, G.; Mishellani, F.; Fusillier, C.; Guerry, M.; Penault-Llorca, F.; Guillot, J.; Vasson, M.-P.

    2005-01-01

    Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

  14. Serum midkine expression in breast cancer patients and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Min Zhang

    2016-01-01

    Objective:To study serum midkine expression in breast cancer patients and its clinical significance.Methods: A total of 45 cases of patients with breast cancer and 45 cases of patients with benign breast tumor were selected for study, breast tumor specimens were collected to detect mRNA content of MK and serum was collected to detect protein content of MK; breast cancer MCF-7 cell lines were cultured and transfected with varying concentrations of MK expression plasmid, and then cell proliferation and apoptosis, VEGF expression in media as well as MMPs and TIMPs expression in cells was detected.Results:MK expression in breast tissue and serum MK content of breast cancer patients were higher than those of benign breast tumor patients, and MK expression in breast tissue and serum MK content of breast cancer patients with TNMⅢ/Ⅳ stage, low/un-differentiation and lymph node metastasis were higher than those of breast cancer patients with TNMⅠ/Ⅱ stage, medium/high differentiation and without lymph node metastasis; MK expression plasmid could dose-dependently increase mRNA content and protein content of MK in breast cancer cell lines, increase cell viability and decrease apoptosis percentage; VEGFA, VEGFB and VEGFC contents in media as well as MMP2 and MMP9 contents in cells of 100.0 μg/mL plasmid group were significantly higher than those of 0 μg/mL plasmid group, and contents of TIMP1 and TIMP2 in cells were significantly lower than those of 0 μg/mL plasmid group.Conclusion:Serum midkine content in breast cancer patients abnormally rises, and high expression of MK can induce breast cancer cell proliferation, inhibit breast cancer cell apoptosis and promote angiogenesis and cell invasion.

  15. MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1.

    Science.gov (United States)

    Wang, Yongxia; Zhang, Zheying; Wang, Jianqiang

    2018-04-20

    Breast cancer is the leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancer cases and has a poorer prognosis than other subtypes. Moreover, the treatment for breast cancer, especially for TNBC, remains unsatisfactory. Therefore, novel therapies are urgently needed. Microribonucleic acids (miRNAs) are a class of biomarkers and therapeutic targets in many types of cancers. In the present study, the expression of miR-384 was explored in GSE58606 and in fresh breast cancer tissues by qPCR. The results showed that miR-384 was decreased in breast cancer, especially in TNBC. The results of MTT, colony formation, soft agar, Transwell migration, wound healing and the tumorigenesis assay demonstranted that overexpression of miR-384 inhibited the proliferation and migration of breast cancer in vitro and in vivo; knockdown of miR-384 enhanced the proliferation and migration of breast cancer. In addition, luciferase assay showed that Activin A receptor type 1 (ACVR1) was a direct target of miR-384 and is involved in the inhibitory effects of miR-384 on breast cancer progression. Furthermore, this study indicated that ACVR1 activated the Wnt/β-catenin signaling pathway in breast cancer. In conclusion, our findings revealed functional and mechanistic links between miR-384 and ACVR1 in the progression of breast cancer. miR-384 not only plays an important role in the progression of breast cancer, but has promise as a potential therapeutic target for breast cancer especially for TNBC.

  16. Selumetinib suppresses cell proliferation, migration and trigger apoptosis, G1 arrest in triple-negative breast cancer cells.

    Science.gov (United States)

    Zhou, Yan; Lin, Shuchen; Tseng, Kuo-Fu; Han, Kun; Wang, Yaling; Gan, Zhi-Hua; Min, Da-Liu; Hu, Hai-Yan

    2016-10-21

    Triple-negative breast cancer (TNBC) has aggressive progression with poor prognosis and ineffective treatments. Selumetinib is an allosteric, ATP-noncompetitive inhibitor of MEK1/2, which has benn known as effective antineoplastic drugs for several malignant tumors. We hypothesized that Selumetinib might be potential drug for TNBC and explore the mechanism. After treated with Selumetinib, the viability and mobility of HCC1937 and MDA-MB-231 were detected by MTT, tunnel, wound-healing assay, transwell assay and FCM methods. MiR array was used to analysis the change of miRs. We predicted and verified CUL1 is the target of miR-302a using Luciferase reporter assay. We also silenced the CUL1 by siRNA, to clarify whether CUL1 take part in the cell proliferation, migration and regulated its substrate TIMP1 and TRAF2. Moreover, after transfection, the antagomir of miR-302a and CUL1 over-expressed plasmid into HCC1937 and MDA-MB-231 cell accompanied with the Selumetinib treatment, we detected the proliferation and migration again. Selumetinib reduce the proliferation, migration, triggered apoptosis and G1 arrest in TNBC cell lines. In this process, the miR-302a was up-regulated and inhibited the CUL1 expression. The later negatively regulated the TIMP1 and TRAF2. As soon as we knockdown miR-302a and over-expression CUL1 in TNBC cells, the cytotoxicity of Selumetinib was reversed. MiR-302a targeted regulated the CUL1 expression and mediated the Selumetinib-induced cytotoxicity of triple-negative breast cancer.

  17. The role of lipolysis stimulated lipoprotein receptor in breast cancer and directing breast cancer cell behavior.

    Directory of Open Access Journals (Sweden)

    Denise K Reaves

    Full Text Available The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by cancer stem cell-like features and low expression of cell junction and adhesion proteins. Herein, we sought to define the role of lipolysis stimulated lipoprotein receptor (LSR in breast cancer and cancer cell behavior as LSR was recently correlated with tumor-initiating features. We show that LSR was expressed in epithelium, endothelium, and stromal cells within the healthy breast tissue, as well as in tumor epithelium. In primary breast tumor bioposies, LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, as well as ERα positive tumors and breast cancer cell lines. LSR levels were significantly reduced in claudin-low breast cancer cell lines and functional studies illustrated that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may promote collective cell migration. Re-introduction of LSR in claudin-low breast cancer cell lines reestablished tight junction protein expression and correlated with transepithelial electrical resistance, thereby reverting claudin-low lines to other intrinsic molecular subtypes. Moreover, overexpression of LSR altered gene expression of pathways involved in transformation and tumorigenesis as well as enhanced proliferation and survival in anchorage independent conditions, highlighting that reestablishment of LSR signaling promotes aggressive/tumor initiating cell behaviors. Collectively, these data highlight a direct role for LSR in driving aggressive breast cancer behavior.

  18. Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation

    International Nuclear Information System (INIS)

    Moerkens, Marja; Zhang, Yinghui; Wester, Lynn; Water, Bob van de; Meerman, John HN

    2014-01-01

    Tamoxifen resistance is a major problem in the treatment of estrogen receptor (ER) α -positive breast cancer patients. Although the mechanisms behind tamoxifen resistance are still not completely understood, clinical data suggests that increased expression of receptor tyrosine kinases is involved. Here, we studied the estrogen and anti-estrogen sensitivity of human breast cancer MCF7 cells that have a moderate, retroviral-mediated, ectopic expression of epidermal growth factor receptor (MCF7-EGFR). Proliferation of MCF7-EGFR and parental cells was induced by 17β-estradiol (E2), epidermal growth factor (EGF) or a combination of these. Inhibition of proliferation under these conditions was investigated with 4-hydroxy-tamoxifen (TAM) or fulvestrant at 10 -12 to 10 -6 M. Cells were lysed at different time points to determine the phosphorylation status of EGFR, MAPK 1/3 , AKT and the expression of ERα. Knockdown of target genes was established using smartpool siRNAs. Transcriptomics analysis was done 6 hr after stimulation with growth factors using Affymetrix HG-U133 PM array plates. While proliferation of parental MCF7 cells could only be induced by E2, proliferation of MCF7-EGFR cells could be induced by either E2 or EGF. Treatment with TAM or fulvestrant did significantly inhibit proliferation of MCF7-EGFR cells stimulated with E2 alone. EGF treatment of E2/TAM treated cells led to a marked cell proliferation thereby overruling the anti-estrogen-mediated inhibition of cell proliferation. Under these conditions, TAM however did still inhibit ERα- mediated transcription. While siRNA-mediated knock-down of EGFR inhibited the EGF- driven proliferation under TAM/E2/EGF condition, knock down of ERα did not. The TAM resistant cell proliferation mediated by the conditional EGFR-signaling may be dependent on the PI3K/Akt pathway but not the MEK/MAPK pathway, since a MEK inhibitor (U0126), did not block the proliferation. Transcriptomic analysis under the various E2/TAM

  19. miR-124-3p functions as a tumor suppressor in breast cancer by targeting CBL

    International Nuclear Information System (INIS)

    Wang, Yanbo; Chen, Luxiao; Wu, Zhenyu; Wang, Minghai; Jin, Fangfang; Wang, Nan; Hu, Xiuting; Liu, Zhengya; Zhang, Chen-Yu; Zen, Ke; Chen, Jiangning; Liang, Hongwei; Zhang, Yujing; Chen, Xi

    2016-01-01

    The origin and development of breast cancer remain complex and obscure. Recently, microRNA (miRNA) has been identified as an important regulator of the initiation and progression of breast cancer, and some studies have shown the essential role of miR-124-3p as a tumor suppressor in breast tumorigenesis. However, the detailed role of miR-124-3p in breast cancer remains poorly understood. Quantitative RT-PCR and western blotting assays were used to measure miR-124-3p and CBL expression levels in breast cancer tissues, respectively. Luciferase reporter assay was employed to validate the direct targeting of CBL by miR-124-3p. Cell proliferation and invasion assays were performed to analyze the biological functions of miR-124-3p and CBL in breast cancer cells. In the present study, we found that miR-124-3p was consistently downregulated in breast cancer tissues. Moreover, we showed that miR-124-3p significantly suppressed the proliferation and invasion of breast cancer cells. In addition, we investigated the molecular mechanism through which miR-124-3p contributes to breast cancer tumorigenesis and identified CBL (Cbl proto-oncogene, E3 ubiquitin protein ligase) as a direct target gene of miR-124-3p. Moreover, we found that ectopic expression of CBL can attenuate the inhibitory effect of miR-124-3p on cell proliferation and invasion in breast cancer cells. This study identified a new regulatory axis in which miR-124-3p and CBL regulate the proliferation and invasion of breast cancer cells. The online version of this article (doi:10.1186/s12885-016-2862-4) contains supplementary material, which is available to authorized users

  20. Effects of vitamin D-binding protein-derived macrophage-activating factor on human breast cancer cells.

    Science.gov (United States)

    Pacini, Stefania; Punzi, Tiziana; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco

    2012-01-01

    Searching for additional therapeutic tools to fight breast cancer, we investigated the effects of vitamin D-binding protein-derived macrophage activating factor (DBP-MAF, also known as GcMAF) on a human breast cancer cell line (MCF-7). The effects of DBP-MAF on proliferation, morphology, vimentin expression and angiogenesis were studied by cell proliferation assay, phase-contrast microscopy, immunohistochemistry and western blotting, and chorioallantoic membrane (CAM) assay. DBP-MAF inhibited human breast cancer cell proliferation and cancer cell-stimulated angiogenesis. MCF-7 cells treated with DBP-MAF predominantly grew in monolayer and appeared to be well adherent to each other and to the well surface. Exposure to DBP-MAF significantly reduced vimentin expression, indicating a reversal of the epithelial/mesenchymal transition, a hallmark of human breast cancer progression. These results are consistent with the hypothesis that the known anticancer efficacy of DBP-MAF can be ascribed to different biological properties of the molecule that include inhibition of tumour-induced angiogenesis and direct inhibition of cancer cell proliferation, migration and metastatic potential.

  1. Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner

    OpenAIRE

    David, Diana; Jagadeeshan, Sankar; Hariharan, Ramkumar; Nair, Asha Sivakumari; Pillai, Radhakrishna Madhavan

    2014-01-01

    Background Smurf2 is a member of the HECT family of E3 ubiquitin ligases that play important roles in determining the competence of cells to respond to TGF- β/BMP signaling pathway. However, besides TGF-β/BMP pathway, Smurf2 regulates a repertoire of other signaling pathways ranging from planar cell polarity during embryonic development to cell proliferation, migration, differentiation and senescence. Expression of Smurf2 is found to be dysregulated in many cancers including breast cancer. Th...

  2. p53 inactivation decreases dependence on estrogen/ERK signalling for proliferation but promotes EMT and susceptility to 3-bromopyruvate in ERα+ breast cancer MCF-7 cells.

    Science.gov (United States)

    Rieber, Manuel; Strasberg-Rieber, Mary

    2014-03-15

    Most breast cancers express the estrogen receptor alpha (ERα(+)), harbor wt TP53, depend on estrogen/ERK signalling for proliferation, and respond to anti-estrogens. However, concomittant activation of the epidermal growth factor receptor (EGFR)/MEK pathway promotes resistance by decreasing estrogen dependence. Previously, we showed that retroviral transduction of mutant p53 R175H into wt TP53 ERα(+) MCF-7 cells induces epidermal growth factor (EGF)-independent proliferation, activation of the EGF receptor (p-EGFR) and some characteristics of epithelial-mesenchymal transition (EMT). To investigate whether p53 inactivation augments ERα(+) cell proliferation in response to restrictive estradiol, chemical MEK inhibition or metabolic inhibitors. Introduction of mutant p53 R175H lowered expression of p53-dependent PUMA and p21WAF1, decreased E-cadherin and cytokeratin 18 associated with EMT, but increased the % of proliferating ERα(+)/Ki67 cells, diminishing estrogen dependence. These cells also exhibited higher proliferation in the presence of MEK-inhibitor UO126, reciprocally correlating with preferential susceptibility to the pyruvate analog 3-bromopyruvate (3-BrPA) without a comparable response to 2-deoxyglucose. p53 siRNA silencing by electroporation in wt TP53 MCF-7 cells also decreased estrogen dependence and response to MEK inhibition, while also conferring susceptibility to 3-BrPA. (a) ERα(+) breast cancer cells dysfunctional for TP53 which proliferate irrespective of low estrogen and chemical MEK inhibition are likely to increase metabolic consumption becoming increasingly susceptible to 3-BrPA; (b) targeting the pyruvate pathway may improve response to endocrine therapy in ERα(+) breast cancer with p53 dysfunction. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  3. EHMT2 is a metastasis regulator in breast cancer.

    Science.gov (United States)

    Kim, Kwangho; Son, Mi-Young; Jung, Cho-Rok; Kim, Dae-Soo; Cho, Hyun-Soo

    2018-02-05

    Various modes of epigenetic regulation of breast cancer proliferation and metastasis have been investigated, but epigenetic mechanisms involved in breast cancer metastasis remain elusive. Thus, in this study, EHMT2 (a histone methyltransferase) was determined to be significantly overexpressed in breast cancer tissues and in Oncomine data. In addition, knockdown of EHMT2 reduced cell migration/invasion and regulated the expression of EMT-related markers (E-cadherin, Claudin 1, and Vimentin). Furthermore, treatment with BIX-01294, a specific inhibitor of EHMT2, affected migration/invasion in MDA-MB-231 cells. Therefore, our findings demonstrate functions of EHMT2 in breast cancer metastasis and suggest that targeting EHMT2 may be an effective therapeutic strategy for preventing breast cancer metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. NUCKS overexpression in breast cancer

    Directory of Open Access Journals (Sweden)

    Kittas Christos

    2009-08-01

    Full Text Available Abstract Background NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR, real-time PCR (qRT-PCR and Western immunoblot analyses in the primary cell cultures developed from the same biopsies. Results The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas in situ (DCIS. It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of NUCKS expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures. Conclusion The results show overexpression of the NUCKS protein in a number of non

  5. The presence of a membrane-bound progesterone receptor sensitizes the estradiol-induced effect on the proliferation of human breast cancer cells.

    Science.gov (United States)

    Neubauer, Hans; Yang, Yang; Seeger, Harald; Fehm, Tanja; Cahill, Michael A; Tong, Xiaowen; Ruan, Xiangyan; Mueck, Alfred O

    2011-08-01

    Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two progestogens on MCF-7 breast cancer cells overexpressing PGRMC1. MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M). E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells. Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.

  6. Breast cancer induced by protracted radiation exposures

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1997-01-01

    The experience at Hiroshima/Nagasaki demonstrated that breast cancer can be induced by single doses of ionizing radiation following latencies of 10-40 years. Several epidemiological studies, usually involving ancillary low-LET radiation to the breast, have demonstrated that breast cancer can be induced by protracted exposures, with similar latencies, and with similar dependencies on dose. Radiobiologically these results suggest that the target cells involved were deficient in repair of low-LET damage even when the protraction was over months to years. Since three-quarters of breast tumors originate in the ducts where their proliferation is controlled by menstrual-cycle timed estrogen/progesterone secretions, these cells periodically were in cycle. Thus, the two main elements of a conceptual model for radon-induced lung cancer -- kinetics and deficient repair -- are satisfied. The model indicates that breast cancer could be the cumulative effect of protracted small exposures, the risk from any one of which ordinarily would be quite small. (author)

  7. Estrogen sulfotransferases in breast and endometrial cancers.

    Science.gov (United States)

    Pasqualini, Jorge Raul

    2009-02-01

    Estrogen sulfotransferase is significantly more active in the normal breast cell (e.g., Human 7) than in the cancer cell (e.g., MCF-7). The data suggest that in breast cancer sulfoconjugated activity is carried out by another enzyme, the SULT1A, which acts at high concentration of the substrates. In breast cancer cells sulfotransferase (SULT) activity can be stimulated by various progestins: medrogestone, promegestone, and nomegestrol acetate, as well as by tibolone and its metabolites. SULT activities can also be controlled by other substances including phytoestrogens, celecoxib, flavonoids (e.g., quercetin, resveratrol), and isoflavones. SULT expression was localized in breast cancer cells, which can be stimulated by promegestone and correlated with the increase of the enzyme activity. The estrogen sulfotransferase (SULT1E1), which acts at nanomolar concentration of estradiol, can inactivate most of this hormone present in the normal breast; however, in the breast cancer cells, the sulfotransferase denoted as SULT1A1 is mainly present, and this acts at micromolar concentrations of E(2). A correlation was postulated among breast cancer cell proliferation, the effect of various progestins, and sulfotransferase stimulation. In conclusion, it is suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers.

  8. Testosterone and breast cancer prevention.

    Science.gov (United States)

    Glaser, R; Dimitrakakis, C

    2015-11-01

    Testosterone (T) is the most abundant biologically active hormone in women. Androgen receptors (AR) are located throughout the body including the breast where T decreases tissue proliferation. However, T can be aromatized to estradiol (E2), which increases proliferation and hence, breast cancer (BCA) risk. Increased aromatase expression and an imbalance in the ratio of stimulatory estrogens to protective androgens impacts breast homeostasis. Recent clinical data supports a role for T in BCA prevention. Women with symptoms of hormone deficiency treated with pharmacological doses of T alone or in combination with anastrozole (A), delivered by subcutaneous implants, had a reduced incidence of BCA. In addition, T combined with A effectively treated symptoms of hormone deficiency in BCA survivors and was not associated with recurrent disease. Most notably, T+A implants placed in breast tissue surrounding malignant tumors significantly reduced BCA tumor size, further supporting T direct antiproliferative, protective and therapeutic effect. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  9. Dietary Natural Products for Prevention and Treatment of Breast Cancer.

    Science.gov (United States)

    Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-07-08

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.

  10. Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation

    Directory of Open Access Journals (Sweden)

    Duangmano Suwit

    2012-10-01

    proliferation of human breast cancer cells through disruption of the microtubule network and down-regulation of c-Myc and nucleophosmin/B23 as well as the perturbation in nucleophosmin/B23 trafficking from the nucleolus to nucleoplasm, resulting in G2/M arrest.

  11. Peroxisome Proliferator Activated Receptor-α/Hypoxia Inducible Factor-1α Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells

    Science.gov (United States)

    Papi, Alessio; Storci, Gianluca; Guarnieri, Tiziana; De Carolis, Sabrina; Bertoni, Sara; Avenia, Nicola; Sanguinetti, Alessandro; Sidoni, Angelo; Santini, Donatella; Ceccarelli, Claudio; Taffurelli, Mario; Orlandi, Marina; Bonafé, Massimiliano

    2013-01-01

    Aims Cancer stem cell biology is tightly connected to the regulation of the pro-inflammatory cytokine network. The concept of cancer stem cells “inflammatory addiction” leads to envisage the potential role of anti-inflammatory molecules as new anti-cancer targets. Here we report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. Methods Breast cancer stem cells were expanded as mammospheres from normal and tumor human breast tissues and from tumorigenic (MCF7) and non tumorigenic (MCF10) human breast cell lines. Mammospheres were exposed to the supernatant of breast tumor and normal mammary gland tissue fibroblasts. Results In mammospheres exposed to the breast tumor fibroblasts supernatant, autocrine tumor necrosis factor-α signalling engenders the functional interplay between peroxisome proliferator activated receptor-α and hypoxia inducible factor-1α (PPARα/HIF1α). The two proteins promote mammospheres formation and enhance each other expression via miRNA130b/miRNA17-5p-dependent mechanism which is antagonized by PPARγ. Further, the PPARα/HIF1α interplay regulates the expression of the pro-inflammatory cytokine interleukin-6, the hypoxia survival factor carbonic anhydrase IX and the plasma lipid carrier apolipoprotein E. Conclusion Our data demonstrate the importance of exploring the role of nuclear receptors (PPARα/PPARγ) in the regulation of pro-inflammatory pathways, with the aim to thwart breast cancer stem cells functioning. PMID:23372804

  12. Phyto-oestrogens and breast cancer chemoprevention

    International Nuclear Information System (INIS)

    Limer, Jane L; Speirs, Valerie

    2004-01-01

    Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

  13. Role of ornithine decarboxylase in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Wensheng Deng; Xian Jiang; Yu Mei; Jingzhong Sun; Rong Ma; Xianxi Liu; Hui Sun; Hui Tian; Xueying Sun

    2008-01-01

    Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis that decarboxylates ornithine to putrescine, has become a promising target for cancer research. The aim of this study is to investigate the role of ODC in breast cancer. We detected expression of ODC in breast cancer tissues and four breast cancer cell lines, and transfected breast cancer cells with an adenoviral vector carrying antisense ODC (rAd-ODC/Ex3as) and examined their growth and migration.ODC was overexpressed in breast cancer tissues and cell lines compared with non-tumor tissues and normal breast epithelial celis,and there was a positive correlation between the level of ODC mRNA and the staging of tumors.The expression of ODC correlated with cyclin D1,a cell cycle protein,in synchronized breast cancer MDA-MB-231 cells.Gene transfection of rAd-ODC/Ex3as markedly down-regulated expression Of ODC and cyclin D1,resulting in suppression of proliferation and cell cycle arrest at G0-G1 phase,and the inhibifion of colony formation,an anchorage-independent growth pattern,and the migratory ability of MDA-MB-231 cells.rAd-ODC/Ex3as also markedly reduced the concentration of putrescine,but not spermidine or spermine,in MDA-MB-231 cells.The results suggested that the ODC gene might act as aprognostic factor for breast cancer and it could be a promising therapeutic target.

  14. Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Andrade, F.O.; Nagamine, M.K.; De Conti, A.; Chaible, L.M.; Fontelles, C.C.; Jordão Junior, A.A.; Vannucchi, H.; Dagli, M.L.Z.; Bassoli, B.K.; Moreno, F.S.; Ong, T.P.

    2012-01-01

    The combined treatment with histone deacetylase inhibitors (HDACi) and retinoids has been suggested as a potential epigenetic strategy for the control of cancer. In the present study, we investigated the effects of treatment with butyrate, a dietary HDACi, combined with vitamin A on MCF-7 human breast cancer cells. Cell proliferation was evaluated by the crystal violet staining method. MCF-7 cells were plated at 5 x 10 4 cells/mL and treated with butyrate (1 mM) alone or combined with vitamin A (10 µM) for 24 to 120 h. Cell proliferation inhibition was 34, 10 and 46% following treatment with butyrate, vitamin A and their combination, respectively, suggesting that vitamin A potentiated the inhibitory activities of butyrate. Furthermore, exposure to this short-chain fatty acid increased the level of histone H3K9 acetylation by 9.5-fold (Western blot), but not of H4K16, and increased the expression levels of p21 WAF1 by 2.7-fold (Western blot) and of RARβ by 2.0-fold (quantitative real-time PCR). Our data show that RARβ may represent a molecular target for butyrate in breast cancer cells. Due to its effectiveness as a dietary HDACi, butyrate should be considered for use in combinatorial strategies with more active retinoids, especially in breast cancers in which RARβ is epigenetically altered

  15. Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, F.O. [Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil); Nagamine, M.K. [Laboratório de Oncologia Experimental, Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); De Conti, A. [Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil); Chaible, L.M. [Laboratório de Oncologia Experimental, Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Fontelles, C.C. [Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil); Jordão Junior, A.A.; Vannucchi, H. [Divisão de Nutrição, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Dagli, M.L.Z. [Laboratório de Oncologia Experimental, Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Bassoli, B.K.; Moreno, F.S.; Ong, T.P. [Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-06-22

    The combined treatment with histone deacetylase inhibitors (HDACi) and retinoids has been suggested as a potential epigenetic strategy for the control of cancer. In the present study, we investigated the effects of treatment with butyrate, a dietary HDACi, combined with vitamin A on MCF-7 human breast cancer cells. Cell proliferation was evaluated by the crystal violet staining method. MCF-7 cells were plated at 5 x 10{sup 4} cells/mL and treated with butyrate (1 mM) alone or combined with vitamin A (10 µM) for 24 to 120 h. Cell proliferation inhibition was 34, 10 and 46% following treatment with butyrate, vitamin A and their combination, respectively, suggesting that vitamin A potentiated the inhibitory activities of butyrate. Furthermore, exposure to this short-chain fatty acid increased the level of histone H3K9 acetylation by 9.5-fold (Western blot), but not of H4K16, and increased the expression levels of p21{sup WAF1} by 2.7-fold (Western blot) and of RARβ by 2.0-fold (quantitative real-time PCR). Our data show that RARβ may represent a molecular target for butyrate in breast cancer cells. Due to its effectiveness as a dietary HDACi, butyrate should be considered for use in combinatorial strategies with more active retinoids, especially in breast cancers in which RARβ is epigenetically altered.

  16. Inhibition of heregulin expression blocks tumorigenicity and metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Miaw-Sheue; Shamon-Taylor, Lisa A.; Mehmi, Inderjit; Tang, Careen K.; Cardillo, Marina; Lupu, Ruth

    2001-12-20

    The growth factor Heregulin (HRG) is expressed in 30% of breast cancer tumors. HRG induces tumorigenicity and metastasis of breast cancer cells. Our investigation into whether blockage of HRG reduces the aggressiveness of breast cancer cells demonstrated that transfection of MDA-MB-231 with an HRG antisense cDNA suppressed proliferation, tumorigenicity, and metastasis. Blockage of the aggressive phenotype is mediated possibly through inactivation of the erbB signaling pathways and a decrease in MMP-9 activity. Our study is the first to report that HRG is a key promoter of breast cancer progression and should be deemed as a potential target in developing therapies for the treatment of breast carcinomas.

  17. Molecular Imaging and Precision Medicine in Breast Cancer.

    Science.gov (United States)

    Chudgar, Amy V; Mankoff, David A

    2017-01-01

    Precision medicine, basing treatment approaches on patient traits and specific molecular features of disease processes, has an important role in the management of patients with breast cancer as targeted therapies continue to improve. PET imaging offers noninvasive information that is complementary to traditional tissue biomarkers, including information about tumor burden, tumor metabolism, receptor status, and proliferation. Several PET agents that image breast cancer receptors can visually demonstrate the extent and heterogeneity of receptor-positive disease and help predict which tumors are likely to respond to targeted treatments. This review presents applications of PET imaging in the targeted treatment of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Polyphenols as Promising Drugs against Main Breast Cancer Signatures

    Directory of Open Access Journals (Sweden)

    María Losada-Echeberría

    2017-11-01

    Full Text Available Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs and epidermal growth factor receptor 2 (HER2. Tumors with none of these receptors are classified as triple negative breast cancer (TNBC and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation.

  19. Polyphenols as Promising Drugs against Main Breast Cancer Signatures

    Science.gov (United States)

    Herranz-López, María; Micol, Vicente

    2017-01-01

    Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs) and epidermal growth factor receptor 2 (HER2). Tumors with none of these receptors are classified as triple negative breast cancer (TNBC) and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation. PMID:29112149

  20. Estrogen induced {beta}-1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hee-Jung [Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan (Korea, Republic of); Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan-city, Gyeongsangnam-do (Korea, Republic of); Chung, Tae-Wook; Kim, Cheorl-Ho [Department of Molecular and Cellular Glycobiology, College of Natural Science, Sungkyunkwan University, Suwon, Kyungki-do (Korea, Republic of); Jeong, Han-Sol; Joo, Myungsoo [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan-city, Gyeongsangnam-do (Korea, Republic of); Youn, BuHyun, E-mail: bhyoun72@pusan.ac.kr [Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan (Korea, Republic of); Ha, Ki-Tae, E-mail: hagis@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan-city, Gyeongsangnam-do (Korea, Republic of)

    2012-10-05

    Highlights: Black-Right-Pointing-Pointer We examined the regulation and biological functions of B4GALT1 expression induced by estrogen. Black-Right-Pointing-Pointer Estrogen-induced B4GALT1 expression through the direct binding of ER-{alpha} to ERE in MCF-7 cells. Black-Right-Pointing-Pointer B4GALT1 expression activates the proliferation of MCF-7 cells via its receptor function. Black-Right-Pointing-Pointer Thus, we suggest B4GALT1 as a molecular target for inhibiting breast cancer proliferation. -- Abstract: Beta 1,4-galactosyltransferase 1 (B4GALT1) synthesizes galactose {beta}-1,4-N-acetylglucosamine (Gal{beta}1-4GlcNAc) groups on N-linked sugar chains of glycoproteins, which play important roles in many biological events, including the proliferation and migration of cancer cells. A previous microarray study reported that this gene is expressed by estrogen treatment in breast cancer. In this study, we examined the regulatory mechanisms and biological functions of estrogen-induced B4GALT1 expression. Our data showed that estrogen-induced expression of B4GALT1 is localized in intracellular compartments and in the plasma membrane. In addition, B4GALT1 has an enzyme activity involved in the production of the Gal{beta}1-4GlcNAc structure. The result from a promoter assay and chromatin immunoprecipitation revealed that 3 different estrogen response elements (EREs) in the B4GALT1 promoter are critical for responsiveness to estrogen. In addition, the estrogen antagonists ICI 182,780 and ER-{alpha}-ERE binding blocker TPBM inhibit the expression of estrogen-induced B4GALT1. However, the inhibition of signal molecules relating to the extra-nuclear pathway, including the G-protein coupled receptors, Ras, and mitogen-activated protein kinases, had no inhibitory effects on B4GALT1 expression. The knock-down of the B4GALT1 gene and the inhibition of membrane B4GALT1 function resulted in the significant inhibition of estrogen-induced proliferation of MCF-7 cells. Considering

  1. Estrogen induced β-1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells

    International Nuclear Information System (INIS)

    Choi, Hee-Jung; Chung, Tae-Wook; Kim, Cheorl-Ho; Jeong, Han-Sol; Joo, Myungsoo; Youn, BuHyun; Ha, Ki-Tae

    2012-01-01

    Highlights: ► We examined the regulation and biological functions of B4GALT1 expression induced by estrogen. ► Estrogen-induced B4GALT1 expression through the direct binding of ER-α to ERE in MCF-7 cells. ► B4GALT1 expression activates the proliferation of MCF-7 cells via its receptor function. ► Thus, we suggest B4GALT1 as a molecular target for inhibiting breast cancer proliferation. -- Abstract: Beta 1,4-galactosyltransferase 1 (B4GALT1) synthesizes galactose β-1,4-N-acetylglucosamine (Galβ1-4GlcNAc) groups on N-linked sugar chains of glycoproteins, which play important roles in many biological events, including the proliferation and migration of cancer cells. A previous microarray study reported that this gene is expressed by estrogen treatment in breast cancer. In this study, we examined the regulatory mechanisms and biological functions of estrogen-induced B4GALT1 expression. Our data showed that estrogen-induced expression of B4GALT1 is localized in intracellular compartments and in the plasma membrane. In addition, B4GALT1 has an enzyme activity involved in the production of the Galβ1-4GlcNAc structure. The result from a promoter assay and chromatin immunoprecipitation revealed that 3 different estrogen response elements (EREs) in the B4GALT1 promoter are critical for responsiveness to estrogen. In addition, the estrogen antagonists ICI 182,780 and ER-α-ERE binding blocker TPBM inhibit the expression of estrogen-induced B4GALT1. However, the inhibition of signal molecules relating to the extra-nuclear pathway, including the G-protein coupled receptors, Ras, and mitogen-activated protein kinases, had no inhibitory effects on B4GALT1 expression. The knock-down of the B4GALT1 gene and the inhibition of membrane B4GALT1 function resulted in the significant inhibition of estrogen-induced proliferation of MCF-7 cells. Considering these results, we propose that estrogen regulates the expression of B4GALT1 through the direct binding of ER-α to ERE and

  2. Cystatin C deficiency suppresses tumor growth in a breast cancer model through decreased proliferation of tumor cells.

    Science.gov (United States)

    Završnik, Janja; Butinar, Miha; Prebanda, Mojca Trstenjak; Krajnc, Aleksander; Vidmar, Robert; Fonović, Marko; Grubb, Anders; Turk, Vito; Turk, Boris; Vasiljeva, Olga

    2017-09-26

    Cysteine cathepsins are proteases that, in addition to their important physiological functions, have been associated with multiple pathologies, including cancer. Cystatin C (CstC) is a major endogenous inhibitor that regulates the extracellular activity of cysteine cathepsins. We investigated the role of cystatin C in mammary cancer using CstC knockout mice and a mouse model of breast cancer induced by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium. We showed that the ablation of CstC reduced the rate of mammary tumor growth. Notably, a decrease in the proliferation of CstC knockout PyMT tumor cells was demonstrated ex vivo and in vitro , indicating a role for this protease inhibitor in signaling pathways that control cell proliferation. An increase in phosphorylated p-38 was observed in CstC knockout tumors, suggesting a novel function for cystatin C in cancer development, independent of the TGF-β pathway. Moreover, proteomic analysis of the CstC wild-type and knockout PyMT primary cell secretomes revealed a decrease in the levels of 14-3-3 proteins in the secretome of knock-out cells, suggesting a novel link between cysteine cathepsins, cystatin C and 14-3-3 proteins in tumorigenesis, calling for further investigations.

  3. Breast cancer risk accumulation starts early: prevention must also.

    Science.gov (United States)

    Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S

    2014-06-01

    Nearly one in four breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. This study follows the literature review methods and format. Exposures during childhood and adolescence affect a woman's long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors is related to breast cancer risk and risk of premalignant proliferative benign lesions. Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention.

  4. Targeting progesterone metabolism in breast cancer with l-proline derived new 14-azasteroids.

    Science.gov (United States)

    Singh, Jyotsana; Singh, Ritesh; Gupta, Preeti; Rai, Smita; Ganesher, Asha; Badrinarayan, Preethi; Sastry, G Narahari; Konwar, Rituraj; Panda, Gautam

    2017-08-15

    Breast cancer cell proliferation is promoted by a variety of mitogenic signals. Classically estrogen is considered as most predominant mitogenic signal in hormone-dependent breast cancer and progesterone is primarily considered to have protective effect. However, it is suggested that some progesterone metabolite may promote breast cancer and progesterone metabolites like 5α-pregnane and 4-pregnene could serve as regulators of estrogen-responsiveness of breast cancer cells. Here, we estimated the potential of alternate targeting of breast cancer via progesterone signalling. l-Proline derived novel 14-azasteroid compounds were screened against MCF-7 and MDA-MB-231 cell lines using MTT assay. In silico studies, cell cycle, Annexin-V-FITC/PI, JC-1 mitochondrial assay, ROS analysis were performed to analyse the impact of hit compound 3b on breast cancer cells. Further, we analysed the impact of hit 3b on the progesterone, its metabolites and enzymes responsible for the conversion of progesterone and its metabolites using ELISA. Data suggests that compound 3b binds and down regulates of 5α-reductase by specifically inhibiting production of progesterone metabolites that are capable of promoting breast cancer proliferation, epithelial mesenchymal transition and migration. This study establishes the proof of concept and generation of new leads for additional targeting of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Wnt signaling in triple-negative breast cancer

    Science.gov (United States)

    Pohl, SÖ-G; Brook, N; Agostino, M; Arfuso, F; Kumar, A P; Dharmarajan, A

    2017-01-01

    Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease. PMID:28368389

  6. Melatonin: an Inhibitor of Breast Cancer

    Science.gov (United States)

    Hill, Steven M.; Belancio, Victoria P.; Dauchy, Robert T.; Xiang, Shulin; Brimer, Samantha; Mao, Lulu; Hauch, Adam; Lundberg, Peter W.; Summers, Whitney; Yuan, Lin; Frasch, Tripp; Blask, David E.

    2015-01-01

    This review discusses recent work on melatonin-mediated circadian regulation and metabolic and molecular signaling mechanisms involved in human breast cancer growth and associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin, via the MT1 receptor, suppresses ERα mRNA expression and ERα transcriptional activity. As well, melatonin regulates the transactivation of other members of the nuclear receptor super-family, estrogen metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (Warburg effect), and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways including inhibition of p38 MAPK and repression of epithelial-to-mesenchymal transition. Studies demonstrate that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models indicate that LEN induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer to drive breast tumors to endocrine and chemotherapeutic resistance. These data provide the strongest understanding and support of the mechanisms underpinning the epidemiologic demonstration of elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LEN. PMID:25876649

  7. Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women.

    Science.gov (United States)

    Sakoda, Lori C; Blackston, Christie R; Xue, Kan; Doherty, Jennifer A; Ray, Roberta M; Lin, Ming Gang; Stalsberg, Helge; Gao, Dao Li; Feng, Ziding; Thomas, David B; Chen, Chu

    2008-05-01

    Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fibrocystic breast conditions. Women diagnosed with breast cancer (n=615) or fibrocystic breast conditions (n=467) were compared to women without clinical breast disease (n=878). We also examined whether these associations differed by menopausal status or by presence of proliferation in the extra-tumoral epithelium among women with breast cancer and in lesions among women with fibrocystic conditions. No overall association of either GST polymorphism with risk of breast cancer or fibrocystic breast conditions was observed. There was some evidence of slightly elevated cancer risk associated with carriage of the GSTM1 null genotype and at least one GSTP1 105-Val allele (OR=1.33, 95% CI, 0.99-1.80), compared to carriage of the GSTM1 non-null and GSTP1 Ile/Ile genotypes. This relationship was stronger in women who had breast cancer with extra-tumoral tissue proliferation (OR=1.77, 95% CI, 1.03-3.04). Our results suggest that GSTM1 and GSTP1 genotypes do not individually influence susceptibility to breast cancer or fibrocystic breast conditions. The observed increased risk of breast cancer associated with joint carriage of the GSTM1 null genotype and GSTP1 105-Val allele needs confirmation in other studies.

  8. Screening for breast cancer with mammography

    International Nuclear Information System (INIS)

    Sickles, E.A.

    1991-01-01

    Mammography is generally accepted as a useful problem-solving clinical tool in characterizing known breast lesions, so that appropriate and timely treatment can be given. However, it remains grossly underutilized at what it does best: screening. The major strengths of mammography are (a) its ability to detect breast cancer at a smaller, potentially more curable stage than any other examination, and (b) its proved efficacy in reducing breast cancer mortality in asymptomatic women aged 40-74. If, as has recently been estimated, screening with mammography and physical examination can be expected to lower breast cancer deaths by 40%-50% among those actually examined (13), then the lives of almost 20,000 U.S. women might be saved each year if screening were to become very widely used. The challenges of the next decade are clear, to mount much more effective campaigns to educate physicians and lay women about the life-saving benefits of breast cancer screening, to devise increasingly effective and lower cost screening strategies, to further improve the current high quality of mammographic imaging despite its increasing proliferation, and to train large numbers of breast imaging specialists to guarantee that the growing case load of screening and problem-solving mammograms is interpreted with a very high level of skill

  9. Ubiquitin-activating enzyme is necessary for 17β-estradiol-induced breast cancer cell proliferation and migration.

    Science.gov (United States)

    Pesiri, Valeria; Totta, Pierangela; Marino, Maria; Acconcia, Filippo

    2014-08-01

    The sex steroid hormone 17β-estradiol (E2) regulates breast cancer (BC) cell proliferation and migration through the activation of a plethora of signal transduction cascades (e.g., PI3K/AKT activation) starting after E2 binding to the estrogen receptor alpha (ERα). The activity of the ubiquitin (Ub)-system modulates many physiological processes (e.g., cell proliferation and migration), and recently, a specific inhibitor (Pyr-41) of the Ub-activating enzyme (E1), which works as the activator of the Ub-based signaling, has been identified to prevent the functions of the Ub-system. Here, by using Pyr-41, we studied the involvement of the Ub-system in E2-induced signaling to proliferation and migration of BC cells. Our data indicate that E1 activity is involved in the E2:ERα signaling important for cell proliferation and migration through the modulation of the E2-evoked activation of the PI3K/AKT and the p38/MAPK pathways. These discoveries indicate a new molecular circuitry that can be further explored to define new opportunities for BC treatment. © 2014 International Union of Biochemistry and Molecular Biology.

  10. The potential of shark bone powder in breast cancer inhibition (pre-clinical study in DMBA-Induced Sprague Dawly Rats)

    Science.gov (United States)

    Bintari, S. H.; Parman, S.; Dafip, M.

    2018-03-01

    Breast cancer is a malignant disease, which lead to second cause of that after cervical cancer in women. To date, lots of drugs and supplement have been developed and consumed by patients. Shark bone is one of the supplements that might inhibit the proliferation of cancer cells. The application of shark bone powder for supplementation in breast cancer cases still becomes controversy; but until now people are still many who consume as a supplement. This study aimed to prove the potency of shark bone powder in the inhibition of breast cancer proliferation and to propose the possibility of its biological mechanism. The pre-clinical experimental study used a controlled posttest controlled design with 25 white rats strains of DML-induced Sprague-Dawley strains. The cancer markers observed were p53, AgNORs, VEGF, Bcl-2, and Cas-3. The test subjects were divided into 3 groups: control group and 2 treatment groups fed modified with 60% and 90% respectively. A pre-clinical trial of shark bone powder showed that there was significant inhibition for the DMBA-induced anti proliferation and breast cell cancer (p breast cancer proliferation lies in concentration 30mg/BB/day.

  11. Small leucine zipper protein functions as a negative regulator of estrogen receptor α in breast cancer.

    Directory of Open Access Journals (Sweden)

    Juyeon Jeong

    Full Text Available The nuclear transcription factor estrogen receptor α (ERα plays a critical role in breast cancer progression. ERα acts as an important growth stimulatory protein in breast cancer and the expression level of ERα is tightly related to the prognosis and treatment of patients. Small leucine zipper protein (sLZIP functions as a transcriptional cofactor by binding to various nuclear receptors, including glucocorticoid receptor, androgen receptor, and peroxisome proliferator-activated receptor γ. However, the role of sLZIP in the regulation of ERα and its involvement in breast cancer progression is unknown. We found that sLZIP binds to ERα and represses the transcriptional activity of ERα in ERα-positive breast cancer cells. sLZIP also suppressed the expression of ERα target genes. sLZIP disrupted the binding of ERα to the estrogen response element of the target gene promoter, resulting in suppression of cell proliferation. sLZIP is a novel co-repressor of ERα, and plays a negative role in ERα-mediated cell proliferation in breast cancer.

  12. Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis

    Directory of Open Access Journals (Sweden)

    Stefan Christen

    2016-10-01

    Full Text Available Cellular proliferation depends on refilling the tricarboxylic acid (TCA cycle to support biomass production (anaplerosis. The two major anaplerotic pathways in cells are pyruvate conversion to oxaloacetate via pyruvate carboxylase (PC and glutamine conversion to α-ketoglutarate. Cancers often show an organ-specific reliance on either pathway. However, it remains unknown whether they adapt their mode of anaplerosis when metastasizing to a distant organ. We measured PC-dependent anaplerosis in breast-cancer-derived lung metastases compared to their primary cancers using in vivo 13C tracer analysis. We discovered that lung metastases have higher PC-dependent anaplerosis compared to primary breast cancers. Based on in vitro analysis and a mathematical model for the determination of compartment-specific metabolite concentrations, we found that mitochondrial pyruvate concentrations can promote PC-dependent anaplerosis via enzyme kinetics. In conclusion, we show that breast cancer cells proliferating as lung metastases activate PC-dependent anaplerosis in response to the lung microenvironment.

  13. Modulation of cholinephosphotransferase activity in breast cancer cell lines by Ro5-4864, a peripheral benzodiazepine receptor agonist

    International Nuclear Information System (INIS)

    Akech, Jacqueline; Roy, Somdutta Sinha; Das, Salil K.

    2005-01-01

    Changes in phospholipid and fatty acid profile are hallmarks of cancer progression. Increase in peripheral benzodiazepine receptor expression has been implicated in breast cancer. The benzodiazepine, Ro5-4864, increases cell proliferation in some breast cancer cell lines. Biosynthesis of phosphatidylcholine (PC) has been identified as a marker for cells proliferating at high rates. Cholinephosphotransferase (CPT) is the terminal enzyme for the de novo biosynthesis of PC. We have addressed here whether Ro5-4864 facilitates some cancer causing mechanisms in breast cancer. We report that cell proliferation increases exponentially in aggressive breast cancer cell lines 11-9-1-4 and BT-549 when treated with nanomolar concentrations of Ro5-4864. This increase is seen within 24 h of treatment, consistent with the cell doubling time in these cells. Ro5-4864 also upregulates c-fos expression in breast cancer cell lines 11-9-1-4 and BT-549, while expression in non-tumorigenic cell line MCF-12A was either basal or slightly downregulated. We further examined the expression of the CPT gene in breast cancer (11-9-1-4, BT-549) and non-tumorigenic cell lines (MCF-12A, MCF-12F). We found that the CPT gene is overexpressed in breast cancer cell lines compared to the non-tumorigenic cell lines. Furthermore, the activity of CPT in forming PC is increased in the breast cancer cell lines cultured for 24 h. Additionally, we examined the CPT activity in the presence of nanomolar concentrations of Ro5-4864. Biosynthesis of PC was increased in breast cancer cell lines upon treatment. We therefore propose that Ro5-4864 facilitates PC formation, a process important in membrane biogenesis for proliferating cells

  14. MicroRNA-223 Targeting STIM1 Inhibits the Biological Behavior of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yanfang Yang

    2018-01-01

    Full Text Available Background/Aims: To investigate the cellular effects and clinical significance of microRNA-223 (miR-223 in breast cancer by targeting stromal interaction molecule1 (STIM1. Methods: Breast cancer cell lines (T47D, MCF-7, SKB-R3, MDA-MB-231 and MDA-MB-435 and a normal breast epithelial cell line (MCF-10A were prepared for this study. MiR-223 mimics, anti-miR-223 and pcDNA 3.1-STIM1 were transiently transfected into cancer cells independently or together, and then RT-qPCR was performed to detect the expressions of miR-223 and STIM1 mRNA, dual-luciferase reporter assay was conducted to examine the effects of miR-223 on STIM1, Western blotting was used to measure the expressions of the STIM1 proteins, MTT and Trans-well assays were performed to detect cell proliferation and invasion. Finally, the correlation of miR-223 and STIM1 was investigated by detecting with ISH and IHC in breast cancer specimens or the corresponding adjacent normal tissues. Results: Compared with normal cells and tissues, breast cancer tissues and cells exhibited significantly lower expression of miR-223, but higher expression of STIM1. MiR-223 could inhibit the proliferation and invasiveness of breast cancer cells by negatively regulating the expressions of STIM1. Reimplantation with STIM1 partially rescued the miRNA-223-induced inhibition of breast cancer cells. Clinical data revealed that high expression of STIM1 and miR-223 was respectively detrimental and beneficial factor impacting patient’s disease-free survival (DFS rather than overall survival (OS. Moreover, Pearson correlation analysis also confirmed that STIM1 was inversely correlated with miR-223. Conclusion: MiR-223 inhibits the proliferation and invasion of breast cancer by targeting STIM1. The miR-223/STIM1 axis could possibly be a potential therapeutic target for treating breast cancer patients.

  15. Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development.

    Directory of Open Access Journals (Sweden)

    Masahito Kawazu

    2011-03-01

    Full Text Available Estrogen is a key regulator of normal function of female reproductive system and plays a pivotal role in the development and progression of breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B constitutes a key component of the estrogen signaling pathway. JMJD2B is expressed in a high proportion of human breast tumors, and that expression levels significantly correlate with estrogen receptor (ER positivity. In addition, 17-beta-estradiol (E2 induces JMJD2B expression in an ERα dependent manner. JMJD2B interacts with ERα and components of the SWI/SNF-B chromatin remodeling complex. JMJD2B is recruited to ERα target sites, demethylates H3K9me3 and facilitates transcription of ER responsive genes including MYB, MYC and CCND1. As a consequence, knockdown of JMJD2B severely impairs estrogen-induced cell proliferation and the tumor formation capacity of breast cancer cells. Furthermore, Jmjd2b-deletion in mammary epithelial cells exhibits delayed mammary gland development in female mice. Taken together, these findings suggest an essential role for JMJD2B in the estrogen signaling, and identify JMJD2B as a potential therapeutic target in breast cancer.

  16. Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Panshi Zhang

    Full Text Available Treatments for triple-negative breast cancer (TNBC are limited; intermediate-conductance calcium-activated potassium (SK4 channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC and western blotting (WB, increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p>0.05. Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p<0.05. Further investigation revealed that treatment with epidermal growth factor (EGF/basic fibroblast growth factor (bFGF caused MDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells.

  17. Effects of Calophyllum inophyllum fruit extract on the proliferation and morphological characteristics of human breast cancer cells MCF-7

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    Shanmugapriya

    2016-04-01

    Full Text Available Objective: To evaluate the antiproliferative activity of Calophyllum inophyllum (C. inophyllum fruit extract against human breast cancer cells MCF-7. Methods: The cytotoxic effect of C. inophyllum fruit extract against MCF-7 cancer cells was evaluated through MTT and CyQuant assays for 24 h and the morphological investigation of treated MCF-7 cells was observed under optical microscope using Giemsa staining. Results: The cytotoxic effect of C. inophyllum fruit extract against MCF-7 cancer cells was evaluated through MTT and CyQuant assays simultaneously for 24 h after treatment, which demonstrated the inhibition of cell viability with the IC50 values of 19.63 µg/mL and 27.54 µg/mL, respectively. The preliminary time-based morphological investigation of MCF-7 cells treated with the IC 50 value (23.59 µg/mL of C. inophyllum fruit extract was observed under an optical microscopy via Giemsa staining, which exhibited prominent histological characteristics of apoptosis. Conclusions: This study clearly proved that the proliferation of human breast cancer cell MCF-7 was inhibited by C. inophyllum fruit extract resulted from the induction of apoptosis in MCF-7 cells.

  18. A Comprehensive Nuclear Receptor Network for Breast Cancer Cells

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    Ralf Kittler

    2013-02-01

    Full Text Available In breast cancer, nuclear receptors (NRs play a prominent role in governing gene expression, have prognostic utility, and are therapeutic targets. We built a regulatory map for 24 NRs, six chromatin state markers, and 14 breast-cancer-associated transcription factors (TFs that are expressed in the breast cancer cell line MCF-7. The resulting network reveals a highly interconnected regulatory matrix where extensive crosstalk occurs among NRs and other breast -cancer-associated TFs. We show that large numbers of factors are coordinately bound to highly occupied target regions throughout the genome, and these regions are associated with active chromatin state and hormone-responsive gene expression. This network also provides a framework for stratifying and predicting patient outcomes, and we use it to show that the peroxisome proliferator-activated receptor delta binds to a set of genes also regulated by the retinoic acid receptors and whose expression is associated with poor prognosis in breast cancer.

  19. Breast cancer risk accumulation starts early – Prevention must also

    Science.gov (United States)

    Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S.

    2014-01-01

    Purpose Nearly 1 in 4 breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. Methods Literature review Results Exposures during childhood and adolescence affect a woman’s long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors are related to breast cancer risk and risk of premalignant proliferative benign lesions. Conclusion Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention. PMID:24820413

  20. Mitotically Active Leiomyoma of the Uterus in a Postmenopausal Breast Cancer Patient Receiving Tamoxifen

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    I-Feng Liu

    2006-06-01

    Conclusion: Endometrial cancer is rarely noted in breast cancer patients taking tamoxifen. Further, none have reported mitotically active leiomyoma of the uterus. From this case, endometrial proliferation and mitotically active leiomyoma of the uterus may be related to tamoxifen therapy, and should not be neglected in breast cancer patients.

  1. The response of breast cancer cells to mesenchymal stem cells: a possible role of inflammation by breast implants.

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    Orciani, Monia; Lazzarini, Raffaella; Scartozzi, Mario; Bolletta, Elisa; Mattioli-Belmonte, Monica; Scalise, Alessandro; Di Benedetto, Giovanni; Di Primio, Roberto

    2013-12-01

    Breast implants are widely used and at times might cause inflammation as a foreign body, followed by fibrous capsule formation around the implant. In cancer, the inflamed stroma is essential for preservation of the tumor. Mesenchymal stem cells can be recruited to sites of inflammation, and their role in cancer development is debated. The authors assessed the effects of inflammation caused by breast implants' effects on tumor. Mesenchymal stem cells were isolated from the fibrous capsules of women who underwent a second operation after 1 year (presenting inflammation) or after 20 years (not presenting inflammation) since initial surgery. After characterization, cells were co-cultured with MCF7, a breast cancer cell line. The expression of genes involved in oncogenesis, proliferation, and epithelial-to-mesenchymal transition was investigated, followed by Western blot analyses. After co-culture with mesenchymal stem cells from the inflamed capsule, MCF7 induced a dose- and time-dependent increase in proliferation. Polymerase chain reaction analyses revealed a dysregulation of genes involved in oncogenesis, proliferation, and epithelial-to-mesenchymal transition. The subsequent evaluation by Western blot did not confirm these results, showing only a modest decrease in the expression of E-cadherin after co-culture with mesenchymal stem cells (both derived from inflamed or control capsules). These data indicate that inflammation caused by breast implants partially affects proliferation of MCF7 but does not influence key mechanisms of tumor development.

  2. Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival.

    Science.gov (United States)

    Pai, Vaibhav P; Marshall, Aaron M; Hernandez, Laura L; Buckley, Arthur R; Horseman, Nelson D

    2009-01-01

    The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs

  3. Evaluation of Vitamin D in Breast Cancer in a Tertiary Care Hospital

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    MN Suma

    2017-10-01

    Full Text Available Introduction: Vitamin D has been implicated to play a very important role in different types of cancers due to its pleotropic effects such as cell proliferation, cell differentiation, apoptosis etc. The implications of vitamin D deficiency are more evident in breast, prostate and colorectal cancer. Studies have revealed vitamin D supplementation reduces the risk of Breast cancer. Aim: The main objective of our study was to find out whether low serum 25-hydroxy vitamin D levels was associated with breast cancer. Materials and Methods: Study group included 25 diagnosed cases of breast cancer. Equal number of age and sex matched healthy persons were included in the control group. Serum 25-hydroxy vitamin D was estimated by electrochemiluminiscence immunoassay. Results: Mean vitamin D levels were low in breast cancer patients, when compared to controls (p-value < 0.05,which shows that low vitamin D levels are associated with increased risk of breast cancer. Conclusion: Our study showed that low levels of vitamin D are associated with breast cancer when compared to apparently healthy controls. Estimation of serum vitamin D in patients with breast cancer might help in the early diagnosis and treatment of breast cancer.

  4. MEK inhibitor effective against proliferation in breast cancer cell.

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    Zhou, Yan; Hu, Hai-Yan; Meng, Wei; Jiang, Ling; Zhang, Xing; Sha, Jing-Jing; Lu, Zhigang; Yao, Yang

    2014-09-01

    The targeted small-molecule drug AZD6244 is an allosteric, ATP-noncompetitive inhibitor of MEK1/2 that has shown activity against several malignant tumors. Here, we report that AZD6244 repressed cell growth and induced apoptosis and G1-phase arrest in the breast cancer cell lines MDA-MB-231 and HCC1937. Using microRNA (miRNA) arrays and quantitative RT-PCR, we found that miR-203 was up-regulated after AZD6244 treatment. In accordance with bioinformatics and luciferase activity analyses, CUL1 was found to be the direct target of miR-203. Furthermore, miR-203 inhibition and CUL1 overexpression reversed the cytotoxicity of AZD6244 on the MDA-MB-231 and HCC1937 cells. Collectively, our data indicate that miR-203 mediates the AZD6244-induced cytotoxicity of breast cancer cells and that the MEK/ERK/miR-203/CUL1 signaling pathway may participate in this process.

  5. Breast cancer and steroid metabolizing enzymes: the role of progestogens.

    Science.gov (United States)

    Pasqualini, Jorge R

    2009-12-01

    It is well documented that breast tissue, both normal and cancerous, contains all the enzymatic systems necessary for the bioformation and metabolic transformation of estrogens, androgens and progesterone. These include sulfatases, aromatase, hydroxysteroid-dehydrogenases, sulfotransferases, hydroxylases and glucuronidases. The control of these enzymes plays an important role in the development and pathogenesis of hormone-dependent breast cancer. As discussed in this review, various progestogens including dydrogesterone and its 20alpha-dihydro-derivative, medrogestone, promegestone, nomegestrol acetate and norelgestromin can reduce intratissular levels of estradiol in breast cancer by blocking sulfatase and 17beta-hydroxysteroid-dehydrogenase type 1 activities. A possible correlation has been postulated between breast cell proliferation and estrogen sulfotransferase activity. Progesterone is largely transformed in the breast; normal breast produces mainly 4-ene derivatives, whereas 5alpha-derivatives are most common in breast cancer tissue. It has been suggested that this specific conversion of progesterone may be involved in breast carcinogenesis. In conclusion, treatment with anti-aromatases combined with anti-sulfatase or 17beta-hydroxysteroid-dehydrogenase type 1 could provide new therapeutic possibilities in the treatment of patients with hormone-dependent breast cancer. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  6. Anti-RhoC siRNAs inhibit the proliferation and invasiveness of breast cancer cells via modulating the KAI1, MMP9, and CXCR4 expression

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    Xu X

    2017-03-01

    Full Text Available Xu-Dong Xu,1 Han-Bin Shen,1 Li Zhu,2 Jian-Qin Lu,2 Lin Zhang,3 Zhi-Yong Luo,3 Ya-Qun Wu3 1Department of Thyroid and Breast Surgery, The Fifth Hospital of Wuhan, Hanyang District, 2Department of Oncology, 3Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China Abstract: Overexpression of RhoC in breast cancer cells indicates poor prognosis. In the present study, we aim to investigate the possible antitumor effects of anti-RhoC small-interfering RNA (siRNA in inflammatory breast cancer cells. In this study, a specific anti-RhoC siRNA was used to inhibit RhoC synthesis. Transfection of anti-RhoC siRNA into two IBC cells SUM149 and SUM190 induced extensive degradation of target mRNA and led to significant decrease in the synthesis of protein. Anti-RhoC siRNA inhibited cell proliferation and invasion, increased cell apoptosis, and induced cell cycle arrest in vitro. Moreover, the transfection of siRNA increased the expression of KAI1 and decreased the expression of MMP9 and CXCR4 in both mRNA and protein levels. Furthermore, transplantation tumor experiments in BALB/c-nu mice showed that intratumoral injection of anti-RhoC siRNA inhibited tumor growth and increased survival rate. Our results suggested that RhoC gene silencing with specific anti-RhoC siRNA would be a potential therapeutic method for metastatic breast cancer. Keywords: gene silencing, proliferation, apoptosis, cell cycle arrest

  7. Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

    International Nuclear Information System (INIS)

    Fleming, Jodie M; Ginsburg, Erika; Oliver, Shannon D; Goldsmith, Paul; Vonderhaar, Barbara K

    2012-01-01

    Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca 2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H 2 O 2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Our data opens new possibilities for hornerin and its proteolytic fragments in the control of mammary cell function and breast

  8. Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

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    Fleming Jodie M

    2012-06-01

    Full Text Available Abstract Background Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. Methods The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H2O2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Results Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Conclusions Our data opens new possibilities for hornerin and its

  9. Estrogens in breast cancer

    International Nuclear Information System (INIS)

    Terzieff, V.; Vázquez, A.

    2004-01-01

    The prolonged exposure to estrogen increases the risk of cancer breast, the precise role of estrogen in the carcinogenesis process is unclear. They are capable of inducing cell proliferation through different channels receptor Estrogen (ER) known, for example through MAPkinasa sensitivity the promoter of proliferation effect depends on the level of RE, or type to â, integrity (mutations may alter its function) and ligand. The different types of estrogens and related compounds have different profile of affinity for RE and effect end. The modulatory role of progestogens proliferation is very complex, and the interaction between the effector pathways of progestin’s, estrogens, EGF and IGF family - maybe others - determines the final effect .. Estrogens are mutagenic per se weak, but is now known for its hepatic metabolism occur highly reactive species such as quinones, and catechol, powerful mutagens in vitro. Direct or indirect genotoxicity probably explains Part of the effects of estrogen on tumor cells. The use of hormone replacement (HTR) increases the risk of CM, as proportional to the time of use. The combination with progestin seems to be increased risk (R R 2). It is unclear the role of phyto estrogens in the prevention the CM. In the male breast is known that the proliferative response to parenchymal different hormonal maneuvers is different. The effect is minimal castration are and maximum with the combination of estrogen and progesterone. It is unclear, however, the risk of the population exposed to hormone therapy for cancer prostate or otherwise

  10. Tiamulin inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of CD73.

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    Yang, Xu; Pei, Shimin; Wang, Huanan; Jin, Yipeng; Yu, Fang; Zhou, Bin; Zhang, Hong; Zhang, Di; Lin, Degui

    2017-04-11

    Metastasis is the leading cause of death in breast cancer patients. CD73, also known as ecto-5'-nucleotidase, plays a critical role in cancer development including metastasis. The existing researches indicate that overexpression of CD73 promotes growth and metastasis of breast cancer. Therefore, CD73 inhibitor can offer a promising treatment for breast cancer. Here, we determined whether tiamulin, which was found to inhibit CD73, was able to suppress breast cancer development and explored the related mechanisms. We firstly measured the effect of tiamulin hydrogen fumarate (THF) on CD73 using high performance liquid chromatography (HPLC). Then, we investigated cell proliferation, migration and invasion in MDA-MB-231 human breast cancer cell line and 4 T1 mouse breast cancer cell line treated with THF by migration assay, invasion assay and activity assay. Besides, we examined the effect of THF on syngeneic mammary tumors of mice by immunohistochemistry. Our data demonstrated that THF inhibited CD73 by decreasing the activity instead of the expression of CD73. In vitro, THF inhibited the proliferation, migration and invasion of MDA-MB-231 and 4 T1 cells by suppressing CD73 activity. In vivo, animal experiments showed that THF treatment resulted in significant reduction in syngeneic tumor growth, microvascular density and lung metastasis rate. Our results indicate that THF inhibits growth and metastasis of breast cancer by blocking the activity of CD73, which may offer a promising treatment for breast cancer therapy.

  11. Oxygen-carbon nanotubes as a chemotherapy sensitizer for paclitaxel in breast cancer treatment.

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    Yongkun Wang

    Full Text Available To study the in vivo and in vitro effects of adding oxygen carbon nanotubes (CNTs to chemotherapy for breast cancer.MCF-7 and SK-BR-3 breast cancer cells were co-cultured with paclitaxel and then exposed to oxygen-CNTs under hypoxic conditions. Cell proliferation, viability, and apoptosis rate were analyzed. Hypoxia-inducible factor-1 alpha (HIF-1α expression was measured using reverse transcription-polymerase chain reaction (RT-PCR and western blot. Nude mice were used as a human breast cancer model to explore the impact of oxygen-CNTs on the in vivo chemotherapeutic effect of paclitaxel.Oxygen-CNTs had no significant effects on the growth of breast cancer cells under normoxia and hypoxia. However, in the hypoxic environment, oxygen-CNTs significantly enhanced the inhibitory effect of paclitaxel on cell proliferation, as well as the apoptosis rate. Under hypoxia, downregulation of HIF-1α and upregulation of caspase-3, caspase-8, caspase-9, LC3 and Beclin-1 were observed when paclitaxel was combined with oxygen-CNT. Furthermore, addition of oxygen-CNTs to chemotherapy was found to significantly reduce tumor weight in the tumor-bearing mice model.Oxygen-CNTs can significantly increase the chemotherapeutic effect of paclitaxel on breast cancer cells. Oxygen-CNTs may be a potential chemosensitizer in breast cancer therapy.

  12. Breast Cancer Prevention

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... from starting. Risk-reducing surgery . General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  13. Breast Cancer Treatment

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  14. Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin.

    Directory of Open Access Journals (Sweden)

    Zhenchuan Song

    Full Text Available Breast cancer is a leading cause of death in women and with an increasing worldwide incidence. Doxorubicin, as a first-line anthracycline-based drug is conventional used on breast cancer clinical chemotherapy. However, the drug resistances limited the curative effect of the doxorubicin therapy in breast cancer patients, but the molecular mechanism determinants of breast cancer resistance to doxorubicin chemotherapy are not fully understood. In order to explore the association between metadherin (MTDH and doxorubicin sensitivity, the differential expressions of MTDH in breast cancer cell lines and the sensitivity to doxorubicin of breast cancer cell lines were investigated.The mRNA and protein expression of MTDH were determined by real-time PCR and Western blot in breast cancer cells such as MDA-MB-231, MCF-7, MDA-MB-435S, MCF-7/ADR cells. Once MTDH gene was knocked down by siRNA in MCF-7/ADR cells and overexpressed by MTDH plasmid transfection in MDA-MB-231 cells, the cell growth and therapeutic sensitivity of doxorubicin were evaluated using MTT and the Cell cycle assay and apoptosis rate was determined by flow cytometry.MCF-7/ADR cells revealed highly expressed MTDH and MDA-MB-231 cells had the lowest expression of MTDH. After MTDH gene was knocked down, the cell proliferation was inhibited, and the inhibitory rate of cell growth and apoptosis rate were enhanced, and the cell cycle arrest during the G0/G1 phase in the presence of doxorubicin treatment. On the other hand, the opposite results were observed in MDA-MB-231 cells with overexpressed MTDH gene.MTDH gene plays a promoting role in the proliferation of breast cancer cells and its high expression may be associated with doxorubicin sensitivity of breast cancer.

  15. Integration of Breast Cancer Secretomes with Clinical Data Elucidates Potential Serum Markers for Disease Detection, Diagnosis, and Prognosis.

    Science.gov (United States)

    Ziegler, Yvonne S; Moresco, James J; Yates, John R; Nardulli, Ann M

    2016-01-01

    Cancer cells secrete factors that influence adjacent cell behavior and can lead to enhanced proliferation and metastasis. To better understand the role of these factors in oncogenesis and disease progression, estrogen and progesterone receptor positive MCF-7 cells, triple negative breast cancer MDA-MB-231, DT22, and DT28 cells, and MCF-10A non-transformed mammary epithelial cells were grown in 3D cultures. A special emphasis was placed on triple negative breast cancer since these tumors are highly aggressive and no targeted treatments are currently available. The breast cancer cells secreted factors of variable potency that stimulated proliferation of the relatively quiescent MCF-10A cells. The conditioned medium from each cell line was subjected to mass spectrometry analysis and a variety of secreted proteins were identified including glycolytic enzymes, proteases, protease inhibitors, extracellular matrix proteins, and insulin-like growth factor binding proteins. An investigation of the secretome from each cell line yielded clues about strategies used for breast cancer proliferation and metastasis. Some of the proteins we identified may be useful in the development of a serum-based test for breast cancer detection, diagnosis, prognosis, and monitoring.

  16. Breast cancer screening

    Science.gov (United States)

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  17. Profilin-1 overexpression in MDA-MB-231 breast cancer cells is associated with alterations in proteomics biomarkers of cell proliferation, survival, and motility as revealed by global proteomics analyses.

    Science.gov (United States)

    Coumans, Joëlle V F; Gau, David; Poljak, Anne; Wasinger, Valerie; Roy, Partha; Moens, Pierre D J

    2014-12-01

    Despite early screening programs and new therapeutic strategies, metastatic breast cancer is still the leading cause of cancer death in women in industrialized countries and regions. There is a need for novel biomarkers of susceptibility, progression, and therapeutic response. Global analyses or systems science approaches with omics technologies offer concrete ways forward in biomarker discovery for breast cancer. Previous studies have shown that expression of profilin-1 (PFN1), a ubiquitously expressed actin-binding protein, is downregulated in invasive and metastatic breast cancer. It has also been reported that PFN1 overexpression can suppress tumorigenic ability and motility/invasiveness of breast cancer cells. To obtain insights into the underlying molecular mechanisms of how elevating PFN1 level induces these phenotypic changes in breast cancer cells, we investigated the alteration in global protein expression profiles of breast cancer cells upon stable overexpression of PFN1 by a combination of three different proteome analysis methods (2-DE, iTRAQ, label-free). Using MDA-MB-231 as a model breast cancer cell line, we provide evidence that PFN1 overexpression is associated with alterations in the expression of proteins that have been functionally linked to cell proliferation (FKPB1A, HDGF, MIF, PRDX1, TXNRD1, LGALS1, STMN1, LASP1, S100A11, S100A6), survival (HSPE1, HSPB1, HSPD1, HSPA5 and PPIA, YWHAZ, CFL1, NME1) and motility (CFL1, CORO1B, PFN2, PLS3, FLNA, FLNB, NME2, ARHGDIB). In view of the pleotropic effects of PFN1 overexpression in breast cancer cells as suggested by these new findings, we propose that PFN1-induced phenotypic changes in cancer cells involve multiple mechanisms. Our data reported here might also offer innovative strategies for identification and validation of novel therapeutic targets and companion diagnostics for persons with, or susceptibility to, breast cancer.

  18. High Salt Intake Attenuates Breast Cancer Metastasis to Lung.

    Science.gov (United States)

    Xu, Yijuan; Wang, Wenzhe; Wang, Minmin; Liu, Xuejiao; Lee, Mee-Hyun; Wang, Mingfu; Zhang, Hao; Li, Haitao; Chen, Wei

    2018-04-04

    Diet-related factors are thought to modify the risk of cancers, while the influence of high salt intake remains largely uncharacterized. Breast cancer is the most common cancer in women worldwide. In the present study, we examined the effect of salt intake on breast cancer by using a 4T1 mouse mammary tumor model. Unexpectedly, both the fitness and the survival rate of the tumor-bearing mice were improved by high salt intake. Similarly, high salt intake suppressed the primary tumor growth as well as metastasis to lung in mice. Mechanistically, high salt intake greatly reduced food intake and thus might exert antitumor effect through mimicking calorie restriction. Immunoblotting showed the lower proliferation marker Ki-67 and the higher expression of the tumor suppressor gene p53 in tumors of high salt intake mice. Importantly, high salt intake might induce hyperosmotic stress, which sensitized breast cancer cells to p53-dependent anoikis. Collectively, our findings raise the possibility that endogenous salt deposition might act as the first-line defense system against breast cancer progression as well as metastasis.

  19. Cell Proliferation (KI-67) Expression Is Associated with Poorer Prognosis in Nigerian Compared to British Breast Cancer Women

    Science.gov (United States)

    Agboola, Ayodeji O. J.; Banjo, Adekumbiola A. F.; Anunobi, Charles C.; Salami, Babatunde; Agboola, Mopelola Deji; Musa, Adewale A.; Nolan, Christopher C.; Rakha, Emad A.; Ellis, Ian O.; Green, Andrew R.

    2013-01-01

    Background. Black women with breast cancer (BC) in Nigeria have higher mortality rate compared with British women. This study investigated prognostic features of cell proliferation biomarker (Ki-67) in Nigerian breast cancer women. Materials and Methods. The protein expression of Ki-67 was investigated in series of 308 Nigerian women, prepared as a tissue microarray (TMA), using immunohistochemistry. Clinic-pathological parameters, biomarkers, and patient outcome of tumours expressing Ki-67 in Nigerian women were correlated with UK grade-matched series. Results. A significantly larger proportion of breast tumours from Nigerian women showed high Ki-67 expression. Those tumours were significantly correlated with negative expression of the steroid hormone receptors (ER and PgR), p21, p27, E-cadherin, BRCA-1, and Bcl-2 (all P < 0.001), but positively associated with EGFR (P = 0.003), p53, basal cytokeratins: CK56, CK14, triple negative, and basal phenotype using Nielsen's classification (all P < 0.001) compared to UK women. Multivariate analyses showed that race was also associated with BCSS independent of tumour size, lymph node status, and ER status. Conclusion. Ki-67 expression was observed to have contributed to the difference in the BCSS in Nigerian compared with British BC women. Therefore, targeting Ki-67 in the indigenous black women with BC might improve the patient outcome in the black women with BC. PMID:23691362

  20. Breast Cancer Overview

    Science.gov (United States)

    ... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Introduction Statistics Medical Illustrations Risk Factors and Prevention ...

  1. Increased Levels of Erythropoietin in Nipple Aspirate Fluid and in Ductal Cells from Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ferdinando Mannello

    2008-01-01

    Full Text Available Background: Erythropoietin (Epo is an important regulator of erythropoiesis, and controls proliferation and differentiation of both erythroid and non-erythroid tissues. Epo is actively synthesized by breast cells during lactation, and also plays a role in breast tissues promoting hypoxia-induced cancer initiation. Our aims are to perform an exploratory investigation on the Epo accumulation in breast secretions from healthy and cancer patients and its localization in breast cancer cells.

  2. Oxidative stress: development and progression of breast cancer:review article

    Directory of Open Access Journals (Sweden)

    Arash Salmaninejad

    2017-04-01

    Full Text Available Breast cancer is the most commonly diagnosed cancer in women worldwide. Enormous advancement has been made over the last decades in understanding the biology of breast cancer. Nevertheless, the molecular mechanisms regulating progression, gaining of invasive and metastatic phenotypes, and therapeutic resistance are still not completely understood. Oxidative stress initiate by disbalance in redox status of body. In this case, increase of free radicals in body cause tissue damage. One of the significant species of free radicals is reactive oxygen species (ROS that produced by various metabolic pathways, comprising aerobic metabolism in the mitochondrial respiratory chain. They play a serious role in cellular physiology and pathophysiology likewise beginning and evolution of numerous types of cancers. ROS overproduction is deleterious to cells, and considered key-factors for the development of numerous diseases, such as cardiovascular disorders, neurodegenerative diseases, and cancer. Cancer cells are commonly submitted to upper ROS levels that further incite malignant phenotype through motivation to preserved proliferation, angiogenesis, death evasion, invasiveness, and metastasis. ROS impress various signaling pathways, comprising mitogenic pathways and growth factors, and also controls numerous cellular processes, containing cell proliferation, thus stimulates the undisciplined growth of cells which inspires the development of tumors and initiates the progression of carcinogenesis. The importance of ROS on breast cancer development and etiology is being increasingly clarified. Nevertheless, fewer consideration has been given to the progress of redox system-targeted strategies for breast cancer treatment. Augmented oxidative stress caused by reactive species can diminish the body’s antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are core factors in the development of cancer. Bimolecular reactions cause

  3. Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer.

    LENUS (Irish Health Repository)

    Mohd Sharial, M S N

    2012-12-01

    Approximately 15%-23% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), which leads to the activation of signaling pathways that stimulate cell proliferation and survival. HER2-targeted therapy has substantially improved outcomes in patients with HER2-positive breast cancer. However, both de novo and acquired resistance are observed.

  4. Breast Cancer -- Male

    Science.gov (United States)

    ... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Introduction Statistics Risk Factors and Prevention ...

  5. Knockdown of TFIIS by RNA silencing inhibits cancer cell proliferation and induces apoptosis

    International Nuclear Information System (INIS)

    Hubbard, Kyle; Catalano, Jennifer; Puri, Raj K; Gnatt, Averell

    2008-01-01

    A common element among cancer cells is the presence of improperly controlled transcription. In these cells, the degree of specific activation of some genes is abnormal, and altering the aberrant transcription may therefore directly target cancer. TFIIS is a transcription elongation factor, which directly binds the transcription motor, RNA Polymerase II and allows it to read through various transcription arrest sites. We report on RNA interference of TFIIS, a transcription elongation factor, and its affect on proliferation of cancer cells in culture. RNA interference was performed by transfecting siRNA to specifically knock down TFIIS expression in MCF7, MCF10A, PL45 and A549 cells. Levels of TFIIS expression were determined by the Quantigene method, and relative protein levels of TFIIS, c-myc and p53 were determined by C-ELISA. Induction of apoptosis was determined by an enzymatic Caspase 3/7 assay, as well as a non-enzymatic assay detecting cytoplasmic mono- and oligonucleosomes. A gene array analysis was conducted for effects of TFIIS siRNA on MCF7 and MCF10A cell lines. Knockdown of TFIIS reduced cancer cell proliferation in breast, lung and pancreatic cancer cell lines. More specifically, TFIIS knockdown in the MCF7 breast cancer cell line induced cancer cell death and increased c-myc and p53 expression whereas TFIIS knockdown in the non-cancerous breast cell line MCF10A was less affected. Differential effects of TFIIS knockdown in MCF7 and MCF10A cells included the estrogenic, c-myc and p53 pathways, as observed by C-ELISA and gene array, and were likely involved in MCF7 cell-death. Although transcription is a fundamental process, targeting select core transcription factors may provide for a new and potent avenue for cancer therapeutics. In the present study, knockdown of TFIIS inhibited cancer cell proliferation, suggesting that TFIIS could be studied as a potential cancer target within the transcription machinery

  6. Tannic Acid Preferentially Targets Estrogen Receptor-Positive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Brian W. Booth

    2013-01-01

    Full Text Available Research efforts investigating the potential of natural compounds in the fight against cancer are growing. Tannic acid (TA belongs to the class of hydrolysable tannins and is found in numerous plants and foods. TA is a potent collagen cross-linking agent; the purpose of this study was to generate TA-cross-linked beads and assess the effects on breast cancer cell growth. Collagen beads were stable at body temperature following crosslinking. Exposure to collagen beads with higher levels of TA inhibited proliferation and induced apoptosis in normal and cancer cells. TA-induced apoptosis involved activation of caspase 3/7 and caspase 9 but not caspase 8. Breast cancer cells expressing the estrogen receptor were more susceptible to the effects of TA. Taken together the results suggest that TA has the potential to become an anti-ER+ breast cancer treatment or preventative agent.

  7. Lipoic Acid Decreases the Viability of Breast Cancer Cells and Activity of PTP1B and SHP2.

    Science.gov (United States)

    Kuban-Jankowska, Alicja; Gorska-Ponikowska, Magdalena; Wozniak, Michal

    2017-06-01

    Protein tyrosine phosphatases PTP1B and SHP2 are potential targets for anticancer therapy, because of the essential role they play in the development of tumors. PTP1B and SHP2 are overexpressed in breast cancer cells, thus inhibition of their activity can be potentially effective in breast cancer therapy. Lipoic acid has been previously reported to inhibit the proliferation of colon, breast and thyroid cancer cells. We investigated the effect of alpha-lipoic acid (ALA) and its reduced form of dihydrolipoic acid (DHLA) on the viability of MCF-7 cancer cells and on the enzymatic activity of PTP1B and SHP2 phosphatases. ALA and DHLA decrease the activity of PTP1B and SHP2, and have inhibitory effects on the viability and proliferation of breast cancer cells. ALA and DHLA can be considered as potential agents for the adjunctive treatment of breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study

    International Nuclear Information System (INIS)

    a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Gonzalo-Calvo, David de; López-Vilaró, Laura; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Nasarre, Laura; Perez-Olabarria, Maitane; Vázquez, Tania; Escuin, Daniel; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Badimon, Lina; Barnadas, Agusti; Lerma, Enrique; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Llorente-Cortés, Vicenta

    2015-01-01

    The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. The objective was to analyze the relationship between intratumor CE content and clinicopathological variables in human breast carcinomas. We classified 30 breast carcinoma samples into three subgroups: 10 luminal-A tumors (ER+/PR+/Her2-), 10 Her-2 tumors (ER-/PR-/Her2+), and 10 triple negative (TN) tumors (ER-/PR-/Her2-). We analyzed intratumor neutral CE, free cholesterol (FC) and triglyceride (TG) content by thin layer chromatography after lipid extraction. RNA and protein levels of lipid metabolism and invasion mediators were analyzed by real time PCR and Western blot analysis. Group-wise comparisons, linear regression and logistic regression models showed a close association between CE-rich tumors and higher histologic grade, Ki-67 and tumor necrosis. CE-rich tumors displayed higher mRNA and protein levels of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1). An increased expression of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in CE-rich tumors was also reported. Intratumor CE accumulation is intimately linked to proliferation and aggressive potential of breast cancer tumors. Our data support the link between intratumor CE content and poor clinical outcome and open the door to new antitumor interventions. The online version of this article (doi:10.1186/s12885-015-1469-5) contains supplementary material, which is available to authorized users

  9. Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

    Science.gov (United States)

    Wu, Mingxiang; Ma, Jie

    2017-04-01

    Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  10. Breast Cancer Surgery

    Science.gov (United States)

    FACTS FOR LIFE Breast Cancer Surgery The goal of breast cancer surgery is to remove the whole tumor from the breast. Some lymph nodes ... might still be in the body. Types of breast cancer surgery There are two types of breast cancer ...

  11. Inhibition of miR-155, a therapeutic target for breast cancer, prevented in cancer stem cell formation.

    Science.gov (United States)

    Zuo, Jiangcheng; Yu, Yalan; Zhu, Man; Jing, Wei; Yu, Mingxia; Chai, Hongyan; Liang, Chunzi; Tu, Jiancheng

    2018-02-06

    Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR. The invasive cell line MDA-MB-231 was used to quantify the expression of miR-155 by tumor-sphere forming experiment. Soft agar colony formation assay and tumor xenografts was used to explore whether the inhibition of miR-155 could reduce proliferation of cancer cells in vivo and vitro. In the study, we found miR-155 was upregulated in BC. Soft agar colony formation assay and tumor xenografts showed inhibition of miR-155 could significantly reduce proliferation of cancer cells in vivo and vitro, which confirmed that miR-155 is an effective therapeutic target of breast cancer. Sphere-forming experiment showed that overexpression of miR-155 significantly correlated with stem-like properties. Expressions of ABCG2, CD44 and CD90 were repressed by inhibition of miR-155, but CD24 was promoted. Interestingly, inhibition of miR-155 rendered MDA-MB-231 cells more sensitive to Doxorubicinol, which resulted in an increase of inhibition rate from 20.23% to 68.72%. Expression of miR-155 not only was a therapeutic target but also was associated with cancer stem cell formation and Doxorubicinol sensitivity. Our results underscore the importance of miR-155 as a therapeutic target and combination of Doxorubicinol and miR-155-silencing would be a potential way to cure breast cancer.

  12. Diet, Stem Cells, and Breast Cancer Prevention

    Science.gov (United States)

    2011-01-01

    pepper [39], flavonoids such as hesperetin and naringenin in citrus fruits and tomatoes [40], isoflavones (e.g., GEN, daidzein) from legumes and red...Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 1996;26:167–81. [41...38], capsaicin from chili pepper [39], flavonoids such as hesperetin and naringenin in citrus fruits and tomatoes [40], isoflavones (e.g., GEN

  13. FoxA1 as a lineage-specific oncogene in luminal type breast cancer

    International Nuclear Information System (INIS)

    Yamaguchi, Noritaka; Ito, Emi; Azuma, Sakura; Honma, Reiko; Yanagisawa, Yuka; Nishikawa, Akira; Kawamura, Mika; Imai, Jun-ichi

    2008-01-01

    The forkhead transcription factor FoxA1 is thought to be involved in mammary tumorigenesis. However, the precise role of FoxA1 in breast cancer development is controversial. We examined expression of FoxA1 in 35 human breast cancer cell lines and compared it with that of ErbB2, a marker of poor prognosis in breast cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by RNA interference significantly suppressed proliferation of ErbB2-negative and FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced the toxic effect of Herceptin on ErbB2-positive cell lines through induction of apoptosis. Taken together with previous data that FoxA1 is a marker of luminal cells in mammary gland, our present results suggest that FoxA1 plays an important role as a lineage-specific oncogene in proliferation of cancer cells derived from mammary luminal cells

  14. [Fibrocystic breast disease--breast cancer sequence].

    Science.gov (United States)

    Habor, V; Habor, A; Copotoiu, C; Panţîru, A

    2010-01-01

    Fibrocystic breast disease has developed a major issue: the breast cancer sequence. Its involvement regarding the increse of breast cancer risk has 2 aspects: it may be either the marker of a prone tissue or a premalignant hystological deffect. Difficult differential diagnosis of benign proliferative breast lession and carcinoma led to the idea of sequency between the two: cancer does not initiate on normal mammary epithelia; it takes several proliferative stages for it to occur. In our series we analized a number of 677 breast surgical procedures where the pathologic examination reveals 115 cases (17%) of coexistence between cancer and fibrocystic breast disease. This aspect has proved to be related to earlier debut of breast cancer, suggesting that epithelial hyperplasia is a risk factor for breast cancer.

  15. Mutation analysis of breast cancer gene BRCA among breast cancer Jordanian females

    International Nuclear Information System (INIS)

    Atoum, Manar F.; Al-Kayed, Sameer A.

    2004-01-01

    To screen mutations of the tumor suppressor breast cancer susceptibility gene 1 (BRCA1) within 3 exons among Jordanian breast cancer females. A total of 135 Jordanian breast cancer females were genetically analyzed by denaturing gradient electrophoresis (DGGE) for mutation detection in 3 BRCA1 exons (2, 11 and 20) between 2000-2002 in Al-Basheer Hospital, Amman, Jordan. Of the studied patients 50 had a family history of breast cancer, 28 had a family history of cancer other than breast cancer, and 57 had no family history of any cancer. Five germline mutations were detected among breast cancer females with a family history of breast cancers (one in exon 2 and 4 mutations in exon 11). Another germline mutation (within exon 11) was detected among breast cancer females with family history of cancer other than breast cancer, and no mutation was detected among breast cancer females with no family history of any cancer or among normal control females. Screening mutations within exon 2, exon 11 and exon 20 showed that most screened mutations were within BRCA1 exon 11 among breast cancer Jordanian families with a family history of breast cancer. (author)

  16. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... slow her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  17. Protein kinase D1 stimulates proliferation and enhances tumorigenesis of MCF-7 human breast cancer cells through a MEK/ERK-dependent signaling pathway

    International Nuclear Information System (INIS)

    Karam, Manale; Legay, Christine; Auclair, Christian; Ricort, Jean-Marc

    2012-01-01

    Protein kinase D1, PKD1, is a novel serine/threonine kinase whose altered expression and dysregulation in many tumors as well as its activation by several mitogens suggest that this protein could regulate proliferation and tumorigenesis. Nevertheless, the precise signaling pathways used are still unclear and the potential direct role of PKD1 in tumor development and progression has not been yet investigated. In order to clarify the role of PKD1 in cell proliferation and tumorigenesis, we studied the effects of PKD1 overexpression in a human adenocarcinoma breast cancer cell line, MCF-7 cells. We demonstrated that overexpression of PKD1 specifically promotes MCF-7 cell proliferation through accelerating G0/G1 to S phase transition of the cell cycle. Moreover, inhibition of endogenous PKD1 significantly reduced cell proliferation. Taken together, these results clearly strengthen the regulatory role of PKD1 in cell growth. We also demonstrated that overexpression of PKD1 specifically diminished serum- and anchorage-dependence for proliferation and survival in vitro and allowed MCF-7 cells to form tumors in vivo. Thus, all these data highlight the central role of PKD1 in biological processes which are hallmarks of malignant transformation. Analysis of two major signaling pathways implicated in MCF-7 cell proliferation showed that PKD1 overexpression significantly increased ERK1/2 phosphorylation state without affecting Akt phosphorylation. Moreover, PKD1 overexpression-stimulated cell proliferation and anchorage-independent growth were totally impaired by inhibition of the MEK/ERK kinase cascade. However, neither of these effects was affected by blocking the PI 3-kinase/Akt signaling pathway. Thus, the MEK/ERK signaling appears to be a determining pathway mediating the biological effects of PKD1 in MCF-7 cells. Taken together, all these data demonstrate that PKD1 overexpression increases the aggressiveness of MCF-7 breast cancer cells through enhancing their oncogenic

  18. Identification of novel LRH-1 target genes in breast cancer cells

    OpenAIRE

    Zhao, Zhe

    2017-01-01

    The orphan nuclear receptor liver receptor homolog-1 (LRH-1) plays important roles in embryonic development, lipid homeostasis and steroidogenesis, and has been implicated in driving several cancers. In breast cancer, LRH-1 is expressed in tumour epithelial cells of invasive ductal carcinomas. We hypothesized that LRH-1 regulates epithelial cell proliferation and invasiveness to drive breast tumour progression. The overall goal of this study was to identify molecular mechanisms regulated by L...

  19. miRNA-205 affects infiltration and metastasis of breast cancer

    International Nuclear Information System (INIS)

    Wang, Zhouquan; Liao, Hehe; Deng, Zhiping; Yang, Po; Du, Ning; Zhanng, Yunfeng; Ren, Hong

    2013-01-01

    Highlights: •We detected expression of miR-205 in breast cancer cell lines and tissue samples. •We suggest miR-205 is downregulated in human breast cancer tissues and MCF7 cells. •We suggest the lower expression of miR-205 play a role in breast cancer onset. •These data suggest that miR-205 directly targets HER3 in human breast cancer. -- Abstract: Background: An increasing number of studies have shown that miRNAs are commonly deregulated in human malignancies, but little is known about the function of miRNA-205 (miR-205) in human breast cancer. The present study investigated the influence of miR-205 on breast cancer malignancy. Methods: The expression level of miR-205 in the MCF7 breast cancer cell line was determined by quantitative (q)RT-PCR. We then analyzed the expression of miR-205 in breast cancer and paired non-tumor tissues. Finally, the roles of miR-205 in regulating tumor proliferation, apoptosis, migration, and target gene expression were studied by MTT assay, flow cytometry, qRT-PCR, Western blotting and luciferase assay. Results: miR-205 was downregulated in breast cancer cells or tissues compared with normal breast cell lines or non-tumor tissues. Overexpression of miR-205 reduced the growth and colony-formation capacity of MCF7 cells by inducing apoptosis. Overexpression of miR-205 inhibited MCF7 cell migration and invasiveness. By bioinformation analysis, miR-205 was predicted to bind to the 3′ untranslated regions of human epidermal growth factor receptor (HER)3 mRNA, and upregulation of miR-205 reduced HER3 protein expression. Conclusion: miR-205 is a tumor suppressor in human breast cancer by post-transcriptional inhibition of HER3 expression

  20. BP1 Homeoprotein Enhances Metastatic Potential in Er-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yebo Fu, Yi Lian, Kyung Soon Kim, Lei Zhang, A. Katharine Hindle, Fred Brody, Robert S. Siegel, Timothy A. McCaffrey, Sidney W. Fu

    2010-01-01

    Full Text Available Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. It was reported that BP1, a homeobox isoform of DLX4, is overexpressed in 80% of breast cancer patients and in 100% of estrogen receptor negative (ER- tumors. The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and tumorigenesis. These findings imply that BP1 may play an important role in ER- breast cancer. I sought to determine the effects and mechanisms of BP1 on cell proliferation and metastasis using ER- Hs578T cells as a model. Cells were transfected with either pcDNA3.2 plasmid containing BP1 gene, or pcDNA3.2 vector, then selected and cloned. Overexpression of BP1 increased cell proliferation rate by 2-5 fold (p<0.005, and enhanced the in vitro invasive activity by 25-65 fold (p<0.001. Microarray experiments were performed to identify differentially expressed genes when BP1 is overexpressed. The gene expression profile of the transfected cell lines were compared, resulting in 71 differentially expressed genes with a fold-change of >=2.0. Of those genes, 49 were up-regulated and 22 were down-regulated. Significant pathways were identified involving cell proliferation and metastasis. These data demonstrated that overexpression of BP1 significantly enhanced cell proliferation and metastatic potential in ER- Hs578T cells. Further analysis with more ER- cell lines and patient samples is warranted to establish BP1 as a therapeutic target.

  1. Validation of expression patterns for nine miRNAs in 204 lymph-node negative breast cancers.

    Directory of Open Access Journals (Sweden)

    Kristin Jonsdottir

    Full Text Available INTRODUCTION: Although lymph node negative (LN- breast cancer patients have a good 10-years survival (∼85%, most of them still receive adjuvant therapy, while only some benefit from this. More accurate prognostication of LN- breast cancer patient may reduce over- and under-treatment. Until now proliferation is the strongest prognostic factor for LN- breast cancer patients. The small molecule microRNA (miRNA has opened a new window for prognostic markers, therapeutic targets and/or therapeutic components. Previously it has been shown that miR-18a/b, miR-25, miR-29c and miR-106b correlate to high proliferation. METHODS: The current study validates nine miRNAs (miR-18a/b miR-25, miR-29c, miR-106b, miR375, miR-424, miR-505 and let-7b significantly correlated with established prognostic breast cancer biomarkers. Total RNA was isolated from 204 formaldehyde-fixed paraffin embedded (FFPE LN- breast cancers and analyzed with quantitative real-time Polymerase Chain Reaction (qPCR. Independent T-test was used to detect significant correlation between miRNA expression level and the different clinicopathological features for breast cancer. RESULTS: Strong and significant associations were observed for high expression of miR-18a/b, miR-106b, miR-25 and miR-505 to high proliferation, oestrogen receptor negativity and cytokeratin 5/6 positivity. High expression of let-7b, miR-29c and miR-375 was detected in more differentiated tumours. Kaplan-Meier survival analysis showed that patients with high miR-106b expression had an 81% survival rate vs. 95% (P = 0.004 for patients with low expression. CONCLUSION: High expression of miR-18a/b are strongly associated with basal-like breast cancer features, while miR-106b can identify a group with higher risk for developing distant metastases in the subgroup of Her2 negatives. Furthermore miR-106b can identify a group of patients with 100% survival within the otherwise considered high risk group of patients with

  2. Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells.

    Science.gov (United States)

    Chang, Hsin-Yi; Li, Ming-Hua; Huang, Tsui-Chin; Hsu, Chia-Lang; Tsai, Shang-Ru; Lee, Si-Chen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-02-06

    Breast cancer is one of the leading cancer-related causes of death worldwide. Treatment of triple-negative breast cancer (TNBC) is complex and challenging, especially when metastasis has developed. In this study, we applied infrared radiation as an alternative approach for the treatment of TNBC. We used middle infrared (MIR) with a wavelength range of 3-5 μm to irradiate breast cancer cells. MIR significantly inhibited cell proliferation in several breast cancer cells but did not affect the growth of normal breast epithelial cells. We performed iTRAQ-coupled LC-MS/MS analysis to investigate the MIR-triggered molecular mechanisms in breast cancer cells. A total of 1749 proteins were identified, quantified, and subjected to functional enrichment analysis. From the constructed functionally enriched network, we confirmed that MIR caused G2/M cell cycle arrest, remodeled the microtubule network to an astral pole arrangement, altered the actin filament formation and focal adhesion molecule localization, and reduced cell migration activity and invasion ability. Our results reveal the coordinative effects of MIR-regulated physiological responses in concentrated networks, demonstrating the potential implementation of infrared radiation in breast cancer therapy.

  3. VAV3 mediates resistance to breast cancer endocrine therapy

    NARCIS (Netherlands)

    H. Aguilar (Helena); A. Urruticoechea (Ander); P. Halonen (Pasi); K. Kiyotani (Kazuma); T. Mushiroda (Taisei); X. Barril (Xavier); J. Serra-Musach (Jordi); A.B.M.M.K. Islam (Abul); L. Caizzi (Livia); L. Di Croce (Luciano); E. Nevedomskaya (Ekaterina); W. Zwart (Wilbert); J. Bostner (Josefine); E. Karlsson (Elin); G. Pérez Tenorio (Gizeh); T. Fornander (Tommy); D.C. Sgroi (Dennis); R. Garcia-Mata (Rafael); M.P.H.M. Jansen (Maurice); N. García (Nadia); N. Bonifaci (Núria); F. Climent (Fina); E. Soler (Eric); A. Rodríguez-Vida (Alejo); M. Gil (Miguel); J. Brunet (Joan); G. Martrat (Griselda); L. Gómez-Baldó (Laia); A.I. Extremera (Ana); J. Figueras; J. Balart (Josep); R. Clarke (Robert); K.L. Burnstein (Kerry); K.E. Carlson (Kathryn); J.A. Katzenellenbogen (John); M. Vizoso (Miguel); M. Esteller (Manel); A. Villanueva (Alberto); A.B. Rodríguez-Peña (Ana); X.R. Bustelo (Xosé); Y. Nakamura (Yusuke); H. Zembutsu (Hitoshi); O. Stål (Olle); R.L. Beijersbergen (Roderick); M.A. Pujana (Miguel)

    2014-01-01

    textabstractIntroduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through

  4. Leptin’s Pro-Angiogenic Signature in Breast Cancer

    International Nuclear Information System (INIS)

    Gonzalez-Perez, Ruben Rene; Lanier, Viola; Newman, Gale

    2013-01-01

    Obesity is linked to increased incidence of breast cancer. The precise causes and mechanisms of these morbid relationships are unknown. Contradictory data on leptin angiogenic actions have been published. However, accumulating evidence would suggest that leptin’s pro-angiogenic effects in cancer play an essential role in the disease. Leptin, the main adipokine secreted by adipose tissue, is also abnormally expressed together with its receptor (OB-R) by breast cancer cells. Leptin induces proliferation and angiogenic differentiation of endothelial cells upregulates VEGF/VEGFR2 and transactivates VEGFR2 independent of VEGF. Leptin induces two angiogenic factors: IL-1 and Notch that can increase VEGF expression. Additionally, leptin induces the secretion and synthesis of proteases and adhesion molecules needed for the development of angiogenesis. Leptin’s paracrine actions can further affect stromal cells and tumor associated macrophages, which express OB-R and secrete VEGF and IL-1, respectively. A complex crosstalk between leptin, Notch and IL-1 (NILCO) that induces VEGF/VEGFR2 is found in breast cancer. Leptin actions in tumor angiogenesis could amplify, be redundant and/or compensatory to VEGF signaling. Current failure of breast cancer anti-angiogenic therapies emphasizes the necessity of targeting the contribution of other pro-angiogenic factors in breast cancer. Leptin’s impact on tumor angiogenesis could be a novel target for breast cancer, especially in obese patients. However, more research is needed to establish the importance of leptin in tumor angiogenesis. This review is focused on updated information on how leptin could contribute to tumor angiogenesis

  5. Breast cancer

    International Nuclear Information System (INIS)

    Tokunaga, Masayoshi

    1992-01-01

    More than 20-year follow-up of A-bomb survivors in Hiroshima and Nagasaki has a crucial role in determining the relationship of radiation to the occurrence of breast cancer. In 1967, Wanebo et al have first reported 27 cases of breast cancer during the period 1950-1966 among the Adult Health Study population of A-bomb survivors. Since then, follow-up surveys for breast cancer have been made using the Life Span Study (LSS) cohort, and the incidence of breast cancer has increased year by year; that is breast cancer was identified in 231 cases by the first LSS series (1950-1969), 360 cases by the second LSS series (1950-1974), 564 cases by the third LSS series (1950-1980), and 816 cases in the fourth LSS series (1950-1085). The third LSS series have revealed a high risk for radiation-induced breast cancer in women aged 10 or less at the time of exposure (ATE). Both relative and absolute risks are found to be decreased with increasing ages ATE. Based on the above-mentioned findings and other studies on persons exposed medical radiation, radiation-induced breast cancer is characterized by the following: (1) the incidence of breast cancer is linearly increased with increasing radiation doses; (2) both relative and absolute risks for breast cancer are high in younger persons ATE; (3) age distribution of breast cancer in proximally exposed A-bomb survivors is the same as that in both distally A-bomb survivors and non-exposed persons, and there is no difference in histology between the former and latter groups. Thus, immature mammary gland cells before the age of puberty are found to be most radiosensitive. (N.K.)

  6. Up-regulation of CNDP2 facilitates the proliferation of colon cancer.

    Science.gov (United States)

    Xue, Conglong; Zhang, Zhenwei; Yu, Honglan; Yu, Miao; Yuan, Kaitao; Yang, Ting; Miao, Mingyong; Shi, Hanping

    2014-05-21

    Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.

  7. Mesenchymal precursor cells maintain the differentiation and proliferation potentials of breast epithelial cells

    Science.gov (United States)

    2014-01-01

    Introduction Stromal-epithelial interactions play a fundamental role in tissue homeostasis, controlling cell proliferation and differentiation. Not surprisingly, aberrant stromal-epithelial interactions contribute to malignancies. Studies of the cellular and molecular mechanisms underlying these interactions require ex vivo experimental model systems that recapitulate the complexity of human tissue without compromising the differentiation and proliferation potentials of human primary cells. Methods We isolated and characterized human breast epithelial and mesenchymal precursors from reduction mammoplasty tissue and tagged them with lentiviral vectors. We assembled heterotypic co-cultures and compared mesenchymal and epithelial cells to cells in corresponding monocultures by analyzing growth, differentiation potentials, and gene expression profiles. Results We show that heterotypic culture of non-immortalized human primary breast epithelial and mesenchymal precursors maintains their proliferation and differentiation potentials and constrains their growth. We further describe the gene expression profiles of stromal and epithelial cells in co-cultures and monocultures and show increased expression of the tumor growth factor beta (TGFβ) family member inhibin beta A (INHBA) in mesenchymal cells grown as co-cultures compared with monocultures. Notably, overexpression of INHBA in mesenchymal cells increases colony formation potential of epithelial cells, suggesting that it contributes to the dynamic reciprocity between breast mesenchymal and epithelial cells. Conclusions The described heterotypic co-culture system will prove useful for further characterization of the molecular mechanisms mediating interactions between human normal or neoplastic breast epithelial cells and the stroma, and will provide a framework to test the relevance of the ever-increasing number of oncogenomic alterations identified in human breast cancer. PMID:24916766

  8. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Juhua Zhou; Yin Zhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy,radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future.

  9. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    JuhuaZhou; YinZhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy, radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future. Cellular & Molecular Immunology.

  10. Breast Cancer

    Science.gov (United States)

    Breast cancer affects one in eight women during their lives. No one knows why some women get breast cancer, but there are many risk factors. Risks that ... who have family members with breast or ovarian cancer may wish to be tested for the genes. ...

  11. 2'-Hydroxyflavanone: A novel strategy for targeting breast cancer.

    Science.gov (United States)

    Singhal, Jyotsana; Nagaprashantha, Lokesh; Chikara, Shireen; Awasthi, Sanjay; Horne, David; Singhal, Sharad S

    2017-09-26

    Breast cancer is the most common cancer in women that is driven by cross-talk with hormonal and cellular signaling pathways. The natural phytochemicals, due to broad-spectrum anti-inflammatory and anti-cancerous properties, present with novel opportunities for targeting breast cancer. Intake of citrus fruits is known to reduce the risk for incidence of breast cancer. Hence, we tested the efficacy of citrus flavonoid 2'-hydroxyflavanone (2HF) in breast cancer. 2HF inhibited survival, clonogenic ability, cell cycle progression and induced apoptosis in breast cancer cells. 2HF also decreased VEGF levels and inhibited migratory capacity of breast cancer cells. Administration of 2HF led to regression of triple-negative MDA-MB-231 tumors in the mice xenograft model. 2HF decreased the levels of RLIP76 both in vitro studies and in vivo MDA-MB-231 xenograft model of breast cancer. Western blot and histopathological analyses of resected tumors showed a decline in the levels of survival and proliferation markers Ki67, pAkt, survivin, and cell cycle proteins CDK4 and cyclin B1. 2HF treatment led to inhibition of angiogenesis as determined by decreased VEGF levels in vitro and angiogenesis marker CD31 in vivo . 2HF reversed the pro-/anti-apoptotic ratio of BAX/BCL-2 by decreasing anti-apoptotic protein BCL-2 and increasing pro-apoptotic proteins BAX and BIM in vivo . 2HF also decreased the mesenchymal markers vimentin and fibronectin along with causing a parallel increase in pro-differentiation protein E-cadherin. Collectively, the ability of 2HF to decrease RLIP76, VEGF and regulate critical proliferative, apoptotic and differentiation proteins together provides strong rationale to further develop 2HF based interventions for targeting breast cancer.

  12. Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis

    International Nuclear Information System (INIS)

    Cai, Dongqing; Cao, Jie; Li, Zhen; Zheng, Xin; Yao, Yao; Li, Wanglin; Yuan, Ziqiang

    2009-01-01

    Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer. cDNA microarray analysis was used to compare the BST2 gene expression between a metastatic to bone human breast cancer cell line (MDA-231BO) and a primary human breast cancer cell line (MDA-231). The BST2 expression in one bone metastatic breast cancer and seven non-bone metastatic breast cancer cell lines were also determined using real-time RT-PCR and Western blot assays. We then employed tissue array to further study the BST2 expression in human breast cancer using array slides containing 20 independent breast cancer tumors that formed metastatic bone lesions, 30 non-metastasis-forming breast cancer tumors, and 8 normal breast tissues. In order to test the feasibility of utilizing BST2 as a serum marker for the presence of bone metastasis in breast cancer, we had measured the BST2 expression levels in human serums by using ELISA on 43 breast cancer patients with bone metastasis, 43 breast cancer patients without bone metastasis, and 14 normal healthy controls. The relationship between cell migration and proliferation and BST2 expression was also studied in a human breast recombinant model system using migration and FACS analysis. The microarray demonstrated over expression of the BST2 gene in the bone metastatic breast cancer cell line (MDA-231BO) compared to the primary human breast cancer cell line (MDA-231). The expression of the BST2 gene was significantly increased in the bone metastatic breast cancer cell lines and tumor tissues compared to non-bone metastatic breast cancer

  13. High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer

    DEFF Research Database (Denmark)

    Rask, Lene; Balslev, Eva; Jørgensen, Stine

    2011-01-01

    features, we performed in situ hybridization and semi-quantitative assessment of the miR-21 signal on 12 LN negative grade I (assumed low risk), and 12 LN positive grade II (high risk) breast cancers. miR-21 was predominantly seen in cancer associated fibroblast-like cells, with no difference in expression......Low-risk and high-risk breast cancer patients are stratified primarily according to their lymph node (LN) status and grading. However, some low-risk patients relapse, and some high-risk patients have a favorable clinical outcome, implying a need for better prognostic and predictive tests. Micro...... RNAs are often aberrantly expressed in cancer and microRNA-21 is upregulated in a variety of cancers, including breast cancer. High miR-21 levels have been associated with poor prognosis. To determine the cellular localization of miR-21 and to compare its expression levels with histopathological...

  14. Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer

    International Nuclear Information System (INIS)

    Xu, Wen-Huan; Liu, Zhe-Bin; Hou, Yi-Feng; Hong, Qi; Hu, Da-Li; Shao, Zhi-Ming

    2014-01-01

    PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated. The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model. PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells. These findings demonstrated inhibiting autophagy together with PA-MSHA might be a promising therapeutic strategy in treating hormone receptor negative breast cancer cells

  15. Metabolic Syndrome and Triple-Negative Breast Cancer: A New Paradigm

    International Nuclear Information System (INIS)

    Davis, A.A.; Kaklamani, V.G.

    2012-01-01

    Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angio genesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC

  16. Metabolic Syndrome and Triple-Negative Breast Cancer: A New Paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Davis, A A; Kaklamani, V G [Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (Ukraine)

    2012-07-01

    Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angio genesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC

  17. Stages of Breast Cancer

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  18. REGγ regulates ERα degradation via ubiquitin–proteasome pathway in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Fan; Liang, Yan [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Bi, Jiong [Laboratory of General Surgery, First Affiliated Hospital, Sun Yet-sen University, Guangzhou 510080 (China); Chen, Li; Zhang, Fan [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cui, Youhong [Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Jiang, Jun, E-mail: jcbd@medmail.com.cn [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2015-01-02

    Highlights: • High expression of REGγ is correlated with ERα status and poor clinical features. • Cell growth, mobility and invasion are significantly impaired by REGγ knockdown. • REGγ indirectly regulates ERα protein expression. - Abstract: REGγ is a proteasome coactivator which regulates proteolytic activity in eukaryotic cells. Abundant lines of evidence have showed that REGγ is over expressed in a number of human carcinomas. However, its precise role in the pathogenesis of cancer is still unclear. In this study, by examining 200 human breast cancer specimens, we demonstrated that REGγ was highly expressed in breast cancers, and the expression of REGγ was positively correlated with breast cancer patient estrogen receptor alpha (ERα) status. Moreover, the expression of REGγ was found positively associated with poor clinical features and low survival rates in ERα positive breast cancer patients. Further cell culture studies using MCF7 and BT474 breast cancer cell lines showed that cell proliferation, motility, and invasion capacities were decreased significantly by REGγ knockdown. Lastly, we demonstrated that REGγ indirectly regulates the degradation of ERα protein via ubiquitin–proteasome pathway. In conclusion, our findings provide the evidence that REGγ expression was positively correlated with ERα status and poor clinical prognosis in ERα positive breast cancer patients. As well, we disclose a new connection between the two molecules that are both highly expressed in most breast cancer cases.

  19. Induction of apoptosis by eugenol in human breast cancer cells

    International Nuclear Information System (INIS)

    Vidhya, N.; Niranjali Devaraj, S.

    2011-01-01

    In the present study, potential anticancer effect of eugenol on inhibition of cell proliferation and induction of apoptosis in human MCF-7 breast cancer cells was investigated. Induction of cell death by eugenol was evaluated following MTT assay and monitoring lactate dehydrogenase released into the culture medium for cell viability and cytotoxicity, giemsa staining for morphological alterations, fluorescence microscopy analysis of cells using ethidium bromide and acridine orange and quantitation of DNA fragments for induction of apoptosis. Effect of eugenol on intracellular redox status of the human breast cancer cells was assessed by determining the level of glutathione and lipid peroxidation products (TBARS). Eugenol treatment inhibited the growth and proliferation of human MCF-7 breast cancer cells through induction of cell death, which was dose and time dependent. Microscopic examination of eugenol treated cells showed cell shrinkage, membrane blebbing and apoptotic body formation. Further, eugenol treatment also depleted the level of intracellular glutathione and increased the level of lipid peroxidation. The dose dependent increase in the percentage of apoptotic cells and DNA fragments suggested that apoptosis was involved in eugenol induced cell death and apoptosis might have played a role in the chemopreventive action of eugenol. (author)

  20. Data of a fluorescent imaging-based analysis of anti-cancer drug effects on three-dimensional cultures of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Junji Itou

    2015-12-01

    Full Text Available Three-dimensional (3D cell culture is a powerful tool to study cell growth under 3D condition. To perform a simple test for anti-cancer drugs in 3D culture, visualization of non-proliferated cells is required. We propose a fluorescent imaging-based assay to analyze cancer cell proliferation in 3D culture. We used a pulse-labeling technique with a photoconvertible fluorescent protein Kaede to identify non-proliferated cells. This assay allows us to observe change in cell proliferation in 3D culture by simple imaging. Using this assay, we obtained the data of the effects of anti-cancer drugs, 5-fluorouracil and PD0332991 in a breast cancer cell line, MCF-7.

  1. Breast cancer

    Science.gov (United States)

    ... can help you know how to prevent breast cancer. Breast implants, using antiperspirants, and wearing underwire bras do not increase the risk for breast cancer. There is also no evidence of a direct ...

  2. Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

    Science.gov (United States)

    Zhao, Xiangshan; Mirza, Sameer; Alshareeda, Alaa; Zhang, Ying; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Kim, Jun Hyun; Mohibi, Shakur; Goswami, Monica; Lele, Subodh M; West, William; Qiu, Fang; Ellis, Ian O; Rakha, Emad A; Green, Andrew R; Band, Hamid; Band, Vimla

    2012-07-01

    Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

  3. Breast Cancer: Treatment Options

    Science.gov (United States)

    ... Breast Cancer > Breast Cancer: Treatment Options Request Permissions Breast Cancer: Treatment Options Approved by the Cancer.Net Editorial ... can be addressed as quickly as possible. Recurrent breast cancer If the cancer does return after treatment for ...

  4. Common breast cancer susceptibility loci are associated with triple negative breast cancer

    Science.gov (United States)

    Stevens, Kristen N.; Vachon, Celine M.; Lee, Adam M.; Slager, Susan; Lesnick, Timothy; Olswold, Curtis; Fasching, Peter A.; Miron, Penelope; Eccles, Diana; Carpenter, Jane E.; Godwin, Andrew K.; Ambrosone, Christine; Winqvist, Robert; Schmidt, Marjanka K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor; Hartmann, Arndt; Beckmann, Matthias W.; Schulz-Wendtland, Rüdiger; Ekici, Arif B.; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Graham, Nikki; Hein, Rebecca; Nickels, Stephan; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Hans-Peter; Konstantopoulou, Irene; Fostira, Florentia; Pectasides, Dimitrios; Dimopoulos, Athanasios M.; Fountzilas, George; Clarke, Christine L.; Balleine, Rosemary; Olson, Janet E.; Fredericksen, Zachary; Diasio, Robert B.; Pathak, Harsh; Ross, Eric; Weaver, JoEllen; Rüdiger, Thomas; Försti, Asta; Dünnebier, Thomas; Ademuyiwa, Foluso; Kulkarni, Swati; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Ko, Yon-Dschun; Van Limbergen, Erik; Janssen, Hilde; Peto, Julian; Fletcher, Olivia; Giles, Graham G.; Baglietto, Laura; Verhoef, Senno; Tomlinson, Ian; Kosma, Veli-Matti; Beesley, Jonathan; Greco, Dario; Blomqvist, Carl; Irwanto, Astrid; Liu, Jianjun; Blows, Fiona M.; Dawson, Sarah-Jane; Margolin, Sara; Mannermaa, Arto; Martin, Nicholas G.; Montgomery, Grant W; Lambrechts, Diether; dos Santos Silva, Isabel; Severi, Gianluca; Hamann, Ute; Pharoah, Paul; Easton, Douglas F.; Chang-Claude, Jenny; Yannoukakos, Drakoulis; Nevanlinna, Heli; Wang, Xianshu; Couch, Fergus J.

    2012-01-01

    Triple negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiological factors which promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome wide association studies (GWAS) display heterogeneity of effect among breast cancer subtypes as defined by estrogen receptor (ER) and progesterone receptor (PR) status. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple negative breast cancer and 4,978 healthy controls. We identified six single nucleotide polymorphisms (SNPs) significantly associated with risk of triple negative breast cancer, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.11) and rs8100241 (19p13.11). Together, our results provide convincing evidence of genetic susceptibility for triple negative breast cancer. PMID:21844186

  5. Breast Cancer Screening

    International Nuclear Information System (INIS)

    Altaf, Fadwa J.

    2004-01-01

    Breast cancer is a very common health problem in Saudi females that can be reduced by early detection through introducing breast cancer screening. Literature review reveals significant reduction in breast cancer incidence and outcome after the beginning of breast cancer screening. The objectives of this article are to highlight the significance of breast cancer screening in different international societies and to write the major guidelines of breast cancer screening in relation to other departments involved with more emphasis on the Pathology Department guidelines in tissue handling, diagnostic criteria and significance of the diagnosis. This article summaries and acknowledges major work carried out before, and recommends similar modified work in order to meet the requirement for the Saudi society. (author)

  6. Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds.

    Science.gov (United States)

    Tungsukruthai, Sucharat; Petpiroon, Nalinrat; Chanvorachote, Pithi

    2018-05-01

    Throughout the world, breast cancer is among the major causes of cancer-related death and is the most common cancer found in women. The development of cancer molecular knowledge has surpassed the novel concept of cancer biology and unraveled principle targets for anticancer drug developments and treatment strategies. Metastatic breast cancer cells acquire their aggressive features through several mechanisms, including augmentation of survival, proliferation, tumorigenicity, and motility-related cellular pathways. Clearly, natural product-derived compounds have since long been recognized as an important source for anticancer drugs, several of which have been shown to have promising anti-metastasis activities by suppressing key molecular features supporting such cell aggressiveness. This review provides the essential details of breast cancer, the molecular-based insights into metastasis, as well as the effects and mechanisms of potential compounds for breast cancer therapeutic approaches. As the abilities of cancer cells to invade and metastasize are addressed as the hallmarks of cancer, compounds possessing anti-metastatic effects, together with their defined molecular drug action could benefit the development of new drugs as well as treatment strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Proliferation and Polarity in Breast Cancer: Untying the GordianKnot

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hong; Radisky, Derek C.; Bissell, Mina J.

    2005-05-09

    Epithelial cancers are associated with genomic instability and alterations in signaling pathways that affect proliferation, apoptosis, and integrity of tissue structure. Overexpression of a number of oncogenic protein kinases has been shown to malignantly transform cells in culture and to cause tumors in vivo, but the interconnected signaling events induced by transformation still awaits detailed dissection. We propose that the network of cellular signaling pathways can be classified into functionally distinct branches, and that these pathways are rewired in transformed cells and tissues after they lose tissue-specific architecture to favor tumor expansion and invasion. Using three-dimensional (3D) culture systems, we recently demonstrated that polarity and proliferation of human mammary epithelial cancer cells were separable consequences of signaling pathways downstream of PI3 kinase.These, and results from a number of other laboratories are beginning to provide insight into how different signaling pathways may become interconnected in normal tissues to allow homeostasis, and how they are disrupted during malignant progression.

  8. Developing Anti-HER2 Vaccines: Breast Cancer Experience.

    Science.gov (United States)

    Al-Awadhi, Aydah; Murray, James Lee; Ibrahim, Nuhad K

    2018-04-25

    Breast cancer accounts for more than one million new cases annually and is the leading cause of death in women globally. HER2 overexpression induces cellular and humoral immune responses against the HER2 protein and is associated with higher tumour proliferation rates. Trastuzumab-based therapies are effectively and widely used as standard of care in HER2-amplified/overexpressed breast cancer patients; one cited mechanism of action is the induction of passive immunity and antibody-dependent cellular cytotoxicity against malignant breast cancer cells. These findings drove the efforts to generate antigen-specific immunotherapy to trigger the patient's immune system to target HER2-overexpressing tumour cells, which led to the development of various vaccines against the HER2 antigen. This manuscript discusses the various anti-HER2 vaccine formulations and strategies and their potential role in the metastatic and adjuvant settings. This article is protected by copyright. All rights reserved. © 2018 UICC.

  9. Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry.

    Directory of Open Access Journals (Sweden)

    Cameron M Scott

    Full Text Available DNA methylation can mimic the effects of both germline and somatic mutations for cancer predisposition genes such as BRCA1 and p16INK4a. Constitutional DNA methylation of the BRCA1 promoter has been well described and is associated with an increased risk of early-onset breast cancers that have BRCA1-mutation associated histological features. The role of methylation in the context of other breast cancer predisposition genes has been less well studied and often with conflicting or ambiguous outcomes. We examined the role of methylation in known breast cancer susceptibility genes in breast cancer predisposition and tumor development. We applied the Infinium HumanMethylation450 Beadchip (HM450K array to blood and tumor-derived DNA from 43 women diagnosed with breast cancer before the age of 40 years and measured the methylation profiles across promoter regions of BRCA1, BRCA2, ATM, PALB2, CDH1, TP53, FANCM, CHEK2, MLH1, MSH2, MSH6 and PMS2. Prior genetic testing had demonstrated that these women did not carry a germline mutation in BRCA1, ATM, CHEK2, PALB2, TP53, BRCA2, CDH1 or FANCM. In addition to the BRCA1 promoter region, this work identified regions with variable methylation at multiple breast cancer susceptibility genes including PALB2 and MLH1. Methylation at the region of MLH1 in these breast cancers was not associated with microsatellite instability. This work informs future studies of the role of methylation in breast cancer susceptibility gene silencing.

  10. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    International Nuclear Information System (INIS)

    Martowicz, Agnieszka; Spizzo, Gilbert; Gastl, Guenther; Untergasser, Gerold

    2012-01-01

    The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAM high breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAM low breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAM high cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAM low cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer

  11. Prognostic molecular markers in early breast cancer

    International Nuclear Information System (INIS)

    Esteva, Francisco J; Hortobagyi, Gabriel N

    2004-01-01

    A multitude of molecules involved in breast cancer biology have been studied as potential prognostic markers. In the present review we discuss the role of established molecular markers, as well as potential applications of emerging new technologies. Those molecules used routinely to make treatment decisions in patients with early-stage breast cancer include markers of proliferation (e.g. Ki-67), hormone receptors, and the human epidermal growth factor receptor 2. Tumor markers shown to have prognostic value but not used routinely include cyclin D 1 and cyclin E, urokinase-like plasminogen activator/plasminogen activator inhibitor, and cathepsin D. The level of evidence for other molecular markers is lower, in part because most studies were retrospective and not adequately powered, making their findings unsuitable for choosing treatments for individual patients. Gene microarrays have been successfuly used to classify breast cancers into subtypes with specific gene expression profiles and to evaluate prognosis. RT-PCR has also been used to evaluate expression of multiple genes in archival tissue. Proteomics technologies are in development

  12. Clinical Trial of Acolbifene in Premenopausal Women at High Risk for Breast Cancer.

    Science.gov (United States)

    Fabian, Carol J; Kimler, Bruce F; Zalles, Carola M; Phillips, Teresa A; Metheny, Trina; Petroff, Brian K; Havighurst, Thomas C; Kim, KyungMann; Bailey, Howard H; Heckman-Stoddard, Brandy M

    2015-12-01

    The purpose of this study was to assess the feasibility of using the selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women. To do so, we assessed change in proliferation in benign breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) as a primary endpoint, along with changes in other risk biomarkers and objective and subjective side effects as secondary endpoints. Twenty-five women with cytologic hyperplasia ± atypia and ≥2% of breast epithelial cells staining positive for Ki-67, received 20 mg acolbifene daily for 6-8 months, and then had benign breast tissue and blood risk biomarkers reassessed. Ki-67 decreased from a median of 4.6% [interquartile range (IQR), 3.1%-8.5%] at baseline to 1.4% (IQR, 0.6%-3.5%) after acolbifene (P breast density. Subjective side effects were minimal with no significant increase in hot flashes, muscle cramps, arthralgias, or fatigue. Objective measures showed a clinically insignificant decrease in lumbar spine bone density (DEXA) and an increase in ovarian cysts but no change in endometrial thickness (sonography). In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen-inducible gene expression but minimal side effects, suggesting a phase IIB placebo-controlled trial evaluating it further for breast cancer prevention. ©2015 American Association for Cancer Research.

  13. Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium.

    Directory of Open Access Journals (Sweden)

    Sheng Zhang

    Full Text Available Supplemental dietary selenium is associated with reduced incidence of many cancers. The antitumor function of selenium is thought to be mediated through selenium-binding protein 1 (SELENBP1. However, the significance of SELENBP1 expression in breast cancer is still largely unknown. A total of 95 normal and tumor tissues assay and 12 breast cancer cell lines were used in this study. We found that SELENBP1 expression in breast cancer tissues is reduced compared to normal control. Low SELENBP1 expression in ER(+ breast cancer patients was significantly associated with poor survival (p<0.01, and SELENBP1 levels progressively decreased with advancing clinical stages of breast cancer. 17-β estradiol (E2 treatment of high SELENBP1-expressing ER(+ cell lines led to a down-regulation of SELENBP1, a result that did not occur in ER(- cell lines. However, after ectopic expression of ER in an originally ER(- cell line, down-regulation of SELENBP1 upon E2 treatment was observed. In addition, selenium treatment resulted in reduced cell proliferation in endogenous SELENBP1 high cells; however, after knocking-down SELENBP1, we observed no significant reduction in cell proliferation. Similarly, selenium has no effect on inhibition of cell proliferation in low endogenous SELENBP1 cells, but the inhibitory effect is regained following ectopic SELENBP1 expression. Furthermore, E2 treatment of an ER silenced high endogenous SELENBP1 expressing cell line showed no abolishment of cell proliferation inhibition upon selenium treatment. These data indicate that SELENBP1 expression is regulated via estrogen and that the cell proliferation inhibition effect of selenium treatment is dependent on the high level of SELENBP1 expression. Therefore, the expression level of SELENBP1 could be an important marker for predicting survival and effectiveness of selenium supplementation in breast cancer. This is the first study to reveal the importance of monitoring SELENBP1 expression

  14. FLI1 Expression in Breast Cancer Cell Lines and Primary Breast Carcinomas is Correlated with ER, PR and HER2

    Directory of Open Access Journals (Sweden)

    Inam Jasim Lafta

    2017-12-01

    Full Text Available FLI1 is a member of ETS family of transcription factors that regulate a variety of normal biologic activities including cell proliferation, differentiation, and apoptosis. The expression of FLI1 and its correlation with well-known breast cancer prognostic markers (ER, PR and HER2 was determined in primary breast tumors as well as four breast cancer lines including: MCF-7, T47D, MDA-MB-231 and MDA-MB-468 using RT-qPCR with either 18S rRNA or ACTB (β-actin for normalization of data. FLI1 mRNA level was decreased in the breast cancer cell lines under study compared to the normal breast tissue; however, Jurkat cells, which were used as a positive control, showed overexpression compared to the normal breast. Regarding primary breast carcinomas, FLI1 is significantly under expressed in all of the stages of breast cancer upon using 18S as an internal control. This FLI1 expression was correlated with ER, PR and HER2 status. In conclusion FLI1 can be exploited as a preliminary marker that can predict the status of ER, PR and HER2 in primary breast tumors.

  15. SCFβ-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate cancer cell proliferation and migration

    Science.gov (United States)

    Tron, Adriana E.; Wang, Zhiwei; Sun, Liankun; Inuzuka, Hiroyuki; Wei, Wenyi

    2013-01-01

    Metastasis suppressor 1 (MTSS1) is an important tumor suppressor protein, and loss of MTSS1 expression has been observed in several types of human cancers. Importantly, decreased MTSS1 expression is associated with more aggressive forms of breast and prostate cancers, and with poor survival rate. Currently, it remains unclear how MTSS1 is regulated in cancer cells, and whether reduced MTSS1 expression contributes to elevated cancer cell proliferation and migration. Here we report that the SCFβ-TRCP regulates MTSS1 protein stability by targeting it for ubiquitination and subsequent destruction via the 26S proteasome. Notably, depletion of either Cullin 1 or β-TRCP1 led to increased levels of MTSS1. We further demonstrated a crucial role for Ser322 in the DSGXXS degron of MTSS1 in governing SCFβ-TRCP-mediated MTSS1 degradation. Mechanistically, we defined that Casein Kinase Iδ (CKIδ) phosphorylates Ser322 to trigger MTSS1's interaction with β-TRCP for subsequent ubiquitination and degradation. Importantly, introducing wild-type MTSS1 or a non-degradable MTSS1 (S322A) into breast or prostate cancer cells with low MTSS1 expression significantly inhibited cellular proliferation and migration. Moreover, S322A-MTSS1 exhibited stronger effects in inhibiting cell proliferation and migration when compared to ectopic expression of wild-type MTSS1. Therefore, our study provides a novel molecular mechanism for the negative regulation of MTSS1 by β-TRCP in cancer cells. It further suggests that preventing MTSS1 degradation could be a possible novel strategy for clinical treatment of more aggressive breast and prostate cancers. PMID:24318128

  16. β-Catenin Mediates Anti-adipogenic and Anticancer Effects of Arctigenin in Preadipocytes and Breast Cancer Cells.

    Science.gov (United States)

    Lee, Jihye; Imm, Jee-Young; Lee, Seong-Ho

    2017-03-29

    Arctigenin is a lignan abundant in Asteraceae plants and has anti-inflammatory, antiobesity, and anticancer activities. Obesity is one of the leading causes of several types of cancers including breast cancer. The current study was performed to investigate if arctigenin suppresses differentiation of preadipocytes and proliferation of breast cancer cells and to explore potential molecular mechanisms. Treatment of arctigenin reduced lipid accumulation in differentiated 3T3-L1 adipocytes in a dose- and time-dependent manner without toxicity. Arctigenin suppressed the expression of peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein-alpha (C/EBPα), perilipin, and fatty acid binding protein 4 (FABP4) in a dose-dependent manner in differentiated 3T3-L1 cells. Both total and unphosphorylated (active) β-catenin were increased in whole cell lysates and the nuclear fraction of differentiated 3T3-L1 cells treated with 25 μM arctigenin. On the other hand, arctigenin decreased proliferation of two human breast cancer cells (MCF-7 and MDA-MB-231). Arctigenin induced apoptosis and decreased expression of total and unphosphorylated (active) β-catenin and cyclin D1 in MCF-7, but not in MDA-MB-231. These data indicate that arctigenin suppressed adipogenesis in preadipocytes and activated apoptosis in estrogen receptor (ER) positive breast cancer cells through modulating expression of β-catenin.

  17. Inheritance of proliferative breast disease in breast cancer kindreds

    International Nuclear Information System (INIS)

    Skolnick, M.H.; Cannon-Albright, L.A.; Goldgar, D.E.; Ward, J.H.; Marshall, C.J.; Schumann, G.B.; Hogle, H.; McWhorter, W.P.; Wright, E.C.; Tran, T.D.; Bishop, D.T.; Kushner, J.P.; Eyre, H.J.

    1990-01-01

    Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer

  18. BMI-1 Promotes Self-Renewal of Radio- and Temozolomide (TMZ)-Resistant Breast Cancer Cells.

    Science.gov (United States)

    Yan, Yanfang; Wang, Ying; Zhao, Pengxin; Ma, Weiyuan; Hu, Zhigang; Zhang, Kaili

    2017-12-01

    Breast cancer is a hormone-dependent malignancy and is the most prevalent cause of cancer-related mortality among females. Radiation therapy and chemotherapy are common treatments of breast cancer. However, tumor relapse and metastasis following therapy are major clinical challenges. The importance of B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) was implicated in cell proliferation, stem cell maintenance, and tumor initiation. We established radio- and temozolomide (TMZ)-resistant (IRC-R) MCF-7 and MDA-MB-231 cell lines to investigate the mechanism involved in therapeutic resistance. Cell proliferation and sphere number were dramatically elevated, and BMI-1 was remarkably upregulated, in IRC-R cells compared to parental cells. Silencing BMI-1 by RNA interference only affected the cell proliferation of IRC-R but not parental cells, suggesting the critical role of BMI-1 in radio- and TMZ resistance. We used a xenograft mice model to elucidate that BMI-1 was necessary in tumor development by assessing tumor volume and Ki67 expression. We found that Hedgehog (Hhg) signaling exerted synergized functions together with BMI-1, implicating the importance of BMI-1 in Hhg signaling. Downregulation of BMI-1 could be an effective strategy to suppress tumor growth, which supports the potential clinical use of targeting BMI-1 in breast cancer treatment.

  19. Early dissemination seeds metastasis in breast cancer

    Science.gov (United States)

    Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

    2016-01-01

    Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

  20. Increased Susceptibility to Apoptosis and Growth Arrest of Human Breast Cancer Cells Treated by a Snake Venom-Loaded Silica Nanoparticles

    Directory of Open Access Journals (Sweden)

    Gamal Badr

    2014-11-01

    Full Text Available Background: The development of effective treatments against metastatic cancers, including breast cancer, is among the most important challenges in current experimental and clinical cancer research. We recently demonstrated that Walterinnesia aegyptia venom (WEV, either alone or in combination with silica nanoparticles (WEV+NP, resulted in the growth arrest and apoptosis of different cancer cell lines. Aims: In the present study, we evaluated the impact of WEV alone and WEV+NP on human breast cancer cells isolated from cancer biopsies. Methods: The potential effects of WEV alone and WEV+NP on the proliferation, induction of apoptosis and generation of free radicals in breast cancer cells isolated from 80 patients clinically diagnosed with breast cancer were evaluated by flow cytometry and ELISA. Results: WEV alone and WEV+NP inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of the breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. In addition, the combination of WEV and NP robustly sensitized the breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS, hydroperoxide and nitric oxide. The combination of WEV with NP significantly enhanced the anti-tumor effect of WEV in breast cancer cells. Conclusion: Our data indicate the therapeutic potential of the nanoparticle-sustained delivery of snake venom for the treatment of breast cancer.

  1. n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1.

    Directory of Open Access Journals (Sweden)

    Tsung-Hua Hsieh

    Full Text Available Environmental hormones play important roles in regulating the expression of genes involved in cell proliferation, drug resistance, and breast cancer risk; however, their precise role in human breast cancer cells during cancer progression remains unclear. To elucidate the effect of the most widely used industrial phthalate, n-butyl benzyl phthalate (BBP, on cancer progression, we evaluated the results of BBP treatment using a whole human genome cDNA microarray and MetaCore software and selected candidate genes whose expression was changed by more than ten-fold by BBP compared with controls to analyze the signaling pathways in human breast cancer initiating cells (R2d. A total of 473 genes were upregulated, and 468 were downregulated. Most of these genes are involved in proliferation, epithelial-mesenchymal transition, and angiogenesis signaling. BBP induced the viability, invasion and migration, and tube formation in vitro, and Matrigel plug angiogenesis in vivo of R2d and MCF-7. Furthermore, the viability and invasion and migration of these cell lines following BBP treatment was reduced by transfection with a small interfering RNA targeting the mRNA for lymphoid enhancer-binding factor 1; notably, the altered expression of this gene consistently differentiated tumors expressing genes involved in proliferation, epithelial-mesenchymal transition, and angiogenesis. These findings contribute to our understanding of the molecular impact of the environmental hormone BBP and suggest possible strategies for preventing and treating human breast cancer.

  2. Male Breast Cancer

    Science.gov (United States)

    ... types of breast cancer that can occur in men include Paget's disease of the nipple and inflammatory breast cancer. Inherited genes that increase breast cancer risk Some men inherit abnormal (mutated) genes from their parents that ...

  3. Tyrosine kinase signalling in breast cancer: Modulation of tyrosine kinase signalling in human breast cancer through altered expression of signalling intermediates

    International Nuclear Information System (INIS)

    Kairouz, Rania; Daly, Roger J

    2000-01-01

    The past decade has seen the definition of key signalling pathways downstream of receptor tyrosine kinases (RTKs) in terms of their components and the protein-protein interactions that facilitate signal transduction. Given the strong evidence that links signalling by certain families of RTKs to the progression of breast cancer, it is not surprising that the expression profile of key downstream signalling intermediates in this disease has also come under scrutiny, particularly because some exhibit transforming potential or amplify mitogenic signalling pathways when they are overexpressed. Reflecting the diverse cellular processes regulated by RTKs, it is now clear that altered expression of such signalling proteins in breast cancer may influence not only cellular proliferation (eg Grb2) but also the invasive properties of the cancer cells (eg EMS1/cortactin)

  4. Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer

    International Nuclear Information System (INIS)

    Mu, Haixi; Wang, Na; Zhao, Lijuan; Li, Shuman; Li, Qianqian; Chen, Ling; Luo, Xinrong; Qiu, Zhu; Li, Lili; Ren, Guosheng; Xu, Yongzhu; Zhou, Xiangyang; Xiang, Tingxiu

    2015-01-01

    Our previous study showed that PLCD1 significantly decreases cell proliferation and affects cell cycle progression in breast cancer cells. In the present study, we aimed to investigate its functional and molecular mechanisms, and whether or not can become a new target for gene therapies. We found reduced PLCD1 protein expression in breast tumor tissues compared with paired surgical margin tissues. PLCD1 promoter CpG methylation was detected in 55 of 96 (57%) primary breast tumors, but not in surgical-margin tissues and normal breast tissues. Ectopic expression of PLCD1 inhibited breast tumor cell proliferation in vivo by inducing apoptosis and suppressed tumor cell migration by regulating cytoskeletal reorganization proteins including RhoA and phospho-cofilin. Furthermore, we found that PLCD1 induced p53 accumulation, increased p27 and p21 protein levels, and cleaved PARP. Finally, we constructed an adenoviral vector expressing PLCD1 (AdH5-PLCD1), which exhibited strong cytotoxicity in breast cancer cells. Our findings provide insights into the development of PLCD1 gene therapies for breast cancer and perhaps, other human cancers. - Highlights: • PLCD1 is downregulated via hypermethylation in breast cancer. • PLCD1 suppressed cell migration by regulating cytoskeletal reorganization proteins. • Adenovirus AdHu5-PLCD1 may be a novel therapeutic option for breast cancer

  5. Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Haixi [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Department of Endocrine and breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Wang, Na; Zhao, Lijuan; Li, Shuman; Li, Qianqian; Chen, Ling; Luo, Xinrong; Qiu, Zhu [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Li, Lili [Cancer Epigenetics Laboratory, Department of Clinical Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute (Hong Kong); Ren, Guosheng [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Department of Endocrine and breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Xu, Yongzhu [Chongqing Health Service Center, Chongqing 400020 (China); Zhou, Xiangyang [The Wistar Institute, Philadelphia, PA (United States); Xiang, Tingxiu, E-mail: xiangtx1@gmail.com [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2015-03-15

    Our previous study showed that PLCD1 significantly decreases cell proliferation and affects cell cycle progression in breast cancer cells. In the present study, we aimed to investigate its functional and molecular mechanisms, and whether or not can become a new target for gene therapies. We found reduced PLCD1 protein expression in breast tumor tissues compared with paired surgical margin tissues. PLCD1 promoter CpG methylation was detected in 55 of 96 (57%) primary breast tumors, but not in surgical-margin tissues and normal breast tissues. Ectopic expression of PLCD1 inhibited breast tumor cell proliferation in vivo by inducing apoptosis and suppressed tumor cell migration by regulating cytoskeletal reorganization proteins including RhoA and phospho-cofilin. Furthermore, we found that PLCD1 induced p53 accumulation, increased p27 and p21 protein levels, and cleaved PARP. Finally, we constructed an adenoviral vector expressing PLCD1 (AdH5-PLCD1), which exhibited strong cytotoxicity in breast cancer cells. Our findings provide insights into the development of PLCD1 gene therapies for breast cancer and perhaps, other human cancers. - Highlights: • PLCD1 is downregulated via hypermethylation in breast cancer. • PLCD1 suppressed cell migration by regulating cytoskeletal reorganization proteins. • Adenovirus AdHu5-PLCD1 may be a novel therapeutic option for breast cancer.

  6. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... white women. Inflammatory breast tumors are frequently hormone receptor negative, which means they cannot be treated with ...

  7. Regulation of Akt/Protein Kinase B Signaling by a Novel Protein Phosphatase in Breast Cancer Cells

    National Research Council Canada - National Science Library

    Brognard, John; Newton, Alexandra

    2008-01-01

    ...: cell proliferation, growth, and apoptosis. Finally, since this phosphatase resides in a location of frequent loss of heterozygosity in breast cancer, we sought to determine if this phosphatase played a role in breast tumorigenesis...

  8. Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Min [Galactophore Department, JingZhou Central Hospital, JingZhou (China); Li, Ruishu, E-mail: liruishu2016@yahoo.com [Forensic Surgery Department, JingZhou Traditional Chinese Medicine Hospital, JingZhou (China); Zhang, Juan [Endocrinology Department, JingZhou Central Hospital, JingZhou (China)

    2016-03-18

    Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.

  9. Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer

    International Nuclear Information System (INIS)

    Yu, Min; Li, Ruishu; Zhang, Juan

    2016-01-01

    Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.

  10. In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells

    International Nuclear Information System (INIS)

    Weigel, Marion T; Maass, Nicolai; Mundhenke, Christoph; Dahmke, Linda; Schem, Christian; Bauerschlag, Dirk O; Weber, Katrin; Niehoff, Peter; Bauer, Maret; Strauss, Alexander; Jonat, Walter

    2010-01-01

    Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction. Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin. The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment. Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer

  11. B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells

    International Nuclear Information System (INIS)

    Wu, Qiang; Kong, Xiang-jun; Xu, Xiao-chun; Lobie, Peter E; Zhu, Tao; Wu, Zheng-sheng; Liu, Xue; Yan, Hong; He, Yin-huan; Ye, Shan; Cheng, Xing-wang; Zhu, Gui-lu; Wu, Wen-yong; Wang, Xiao-nan

    2014-01-01

    B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer

  12. The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes.

    Science.gov (United States)

    Wen, Shu Wen; Sceneay, Jaclyn; Lima, Luize Goncalves; Wong, Christina S F; Becker, Melanie; Krumeich, Sophie; Lobb, Richard J; Castillo, Vanessa; Wong, Ke Ni; Ellis, Sarah; Parker, Belinda S; Möller, Andreas

    2016-12-01

    Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45 + bone marrow-derived cells. Subsequent long-term conditioning of naïve mice with exosomes from highly metastatic breast cancer cells revealed the accumulation of myeloid-derived suppressor cells in the lung and liver. This favorable immune suppressive microenvironment was capable of promoting metastatic colonization in the lung and liver, an effect not observed from exosomes derived from nonmetastatic cells and liposome control vesicles. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation and inhibited NK cell cytotoxicity, and hence likely suppressed the anticancer immune response in premetastatic organs. Together, our findings provide novel insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to immune suppression and promotion of metastases. Cancer Res; 76(23); 6816-27. ©2016 AACR. ©2016 American Association for Cancer Research.

  13. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    Science.gov (United States)

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.; Fidler, Isaiah J.; Cantley, Lewis C.; Locasale, Jason W.; Weihua, Zhang

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the non-oxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBPs) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis, and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. PMID:25511375

  14. Male Breast Cancer

    Science.gov (United States)

    Although breast cancer is much more common in women, men can get it too. It happens most often to men between ... 60 and 70. Breast lumps usually aren't cancer. However, most men with breast cancer have lumps. ...

  15. Expression of the breast cancer resistance protein in breast cancer

    NARCIS (Netherlands)

    Faneyte, Ian F.; Kristel, Petra M. P.; Maliepaard, Marc; Scheffer, George L.; Scheper, Rik J.; Schellens, Jan H. M.; van de Vijver, Marc J.

    2002-01-01

    PURPOSE: The breast cancer resistance protein (BCRP) is involved in in vitro multidrug resistance and was first identified in the breast cancer cell line MCF7/AdrVp. The aim of this study was to investigate the role of BCRP in resistance of breast cancer to anthracycline treatment. EXPERIMENTAL

  16. In vitro study of combined cilengitide and radiation treatment in breast cancer cell lines

    International Nuclear Information System (INIS)

    Lautenschlaeger, Tim; Perry, James; Peereboom, David; Li, Bin; Ibrahim, Ahmed; Huebner, Alexander; Meng, Wei; White, Julia; Chakravarti, Arnab

    2013-01-01

    Brain metastasis from breast cancer poses a major clinical challenge. Integrins play a role in regulating adhesion, growth, motility, and survival, and have been shown to be critical for metastatic growth in the brain in preclinical models. Cilengitide, an αvβ3/αvβ5 integrin inhibitor, has previously been studied as an anti-cancer drug in various tumor types. Previous studies have shown additive effects of cilengitide and radiation in lung cancer and glioblastoma cell lines. The ability of cilengitide to enhance the effects of radiation was examined preclinically in the setting of breast cancer to assess its possible efficacy in the setting of brain metastasis from breast cancer. Our panel of breast cells was composed of four cell lines: T-47D (ER/PR+, Her2-, luminal A), MCF-7 (ER/PR+, Her2-, luminal A), MDA-MB-231 (TNBC, basal B), MDA-MB-468 (TNBC, basal A). The presence of cilengitide targets, β3 and β5 integrin, was first determined. Cell detachment was determined by cell counting, cell proliferation was determined by MTS proliferation assay, and apoptosis was measured by Annexin V staining and flow cytometry. The efficacy of cilengitide treatment alone was analyzed, followed by assessment of combined cilengitide and radiation treatment. Integrin β3 knockdown was performed, followed by cilengitide and radiation treatment to test for incomplete target inhibition by cilengitide, in high β3 expressing cells. We observed that all cell lines examined expressed both β3 and β5 integrin and that cilengitide was able to induce cell detachment and reduced proliferation in our panel. Annexin V assays revealed that a portion of these effects was due to cilengitide-induced apoptosis. Combined treatment with cilengitide and radiation served to further reduce proliferation compared to either treatment alone. Following β3 integrin knockdown, radiosensitization in combination with cilengitide was observed in a previously non-responsive cell line (MDA-MB-231

  17. Urtica dioica Extract Inhibits Proliferation and Induces Apoptosis and Related Gene Expression of Breast Cancer Cells In Vitro and In Vivo.

    Science.gov (United States)

    Mohammadi, Ali; Mansoori, Behzad; Baradaran, Pooneh Chokhachi; Khaze, Vahid; Aghapour, Mahyar; Farhadi, Mehrdad; Baradaran, Behzad

    2017-10-01

    Currently, because the prevalence of breast cancer and its consequent mortality has increased enormously in the female population, a number of studies have been designed to identify natural products with special antitumor properties. The main purpose of the present study was to determine the effect of Urtica dioica on triggering apoptosis and diminishing growth, size, and weight of the tumor in an allograft model of BALB/c mice. In the present study, a BALB/c mouse model of breast cancer (4T1) was used. After emergence of tumor, 2 groups of mice received the extract, 1 group at a dose of 10 mg/kg and 1 group at a dose of 20 mg/kg, by intraperitoneal injection for 28 days. During the test and after removal of the tumor mass, the size and weight of the tumor were measured. To assess the induction of apoptosis in the cancer cells, the TUNEL (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling) assay was performed. The Ki-67 test was used to evaluate tumor proliferation. The results showed that the tumor size in the mice treated with the extract decreased significantly. The weight of the tumor mass in the treated mice after resection was less than that in the control group. The TUNEL assay findings revealed that apoptosis occurred in the treated group. The Ki-67 test findings also demonstrated that administration of the extract suppressed the growth of tumor cells. These results suggest that U. dioica extract can decrease the growth of breast tumors and induce apoptosis in tumor cells; thus, it might represent an ideal therapeutic tool for breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Chemokines: novel targets for breast cancer metastasis

    Science.gov (United States)

    Ali, Simi; Lazennec, Gwendal

    2007-01-01

    Recent studies have highlighted the possible involvement of chemokines and their receptors in breast cancer progression and metastasis. Chemokines and their receptors constitute a superfamily of signalling factors whose prognosis value in breast cancer progression remains unclear. We will examine here the expression pattern of chemokines and their receptors in mammary gland physiology and carcinogenesis. The nature of the cells producing chemokines or harboring chemokine receptors appears to be crucial in certain conditions for example, the infiltration of the primary tumor by leukocytes and angiogenesis. In addition, chemokines, their receptors and the interaction with glycosaminoglycan (GAGs) are key players in the homing of cancer cells to distant metastasis sites. Several lines of evidence, including in vitro and in vivo models, suggest that the mechanism of action of chemokines in cancer development involves the modulation of proliferation, apoptosis, invasion, leukocyte recruitment or angiogenesis. Furthermore, we will discuss the regulation of chemokine network in tumor neovascularity by decoy receptors. The reasons accounting for the deregulation of chemokines and chemokine receptors expression in breast cancer are certainly crucial for the comprehension of chemokine role in breast cancer and are in several cases linked to estrogen receptor status. The targeting of chemokines and chemokine receptors by antibodies, small molecule antagonists, viral chemokine binding proteins and heparins appears as promising tracks to develop therapeutic strategies. Thus there is significant interest in developing strategies to antagonize the chemokine function, and an opportunity to interfere with metastasis, the leading cause of death in most patients. PMID:17717637

  19. Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer.

    Science.gov (United States)

    Vlug, Eva J; van de Ven, Robert A H; Vermeulen, Jeroen F; Bult, Peter; van Diest, Paul J; Derksen, Patrick W B

    2013-10-01

    Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells. In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p cancers and conditional mouse models of human lobular breast cancer. Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer.

  20. Potential Biomarker of L type Amino Acid Transporter 1 in Breast Cancer Progression

    International Nuclear Information System (INIS)

    Liang, Zhongxing; Cho, Heidi T.; Williams, Larry; Zhu, Aizhi; Liang, Ke; Huang, Ke; Wu, Hui; Jiang, Chunsu; Hong, Samuel; Crowe, Ronald; Goodman, Mark M.; Shim, Hyunsuk

    2011-01-01

    L type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with 1 amino 3 [ 18F ]fluorocyclo butane 1 carboxylic acid ([ 18F ]FACBC) PET was assessed for its diagnostic biomarker potential. Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced stage breast cancer. Furtermore, the blockade of LAT1 with its inhibitor, 2 amino bicyclo[2.2.1]heptane 2 carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, [ 18F ]FACBC, has been demonstrated to be an excellent PET tracer for the non invasive imaging og malignant breast cancer using an orthotopic animal model. The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. [ 18F ]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging

  1. Increasing Breast Cancer Surveillance among African American Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Thompson, Hayley

    2005-01-01

    ...; they also are at considerable risk for breast cancer recurrence. According to the American Society of Clinical Oncology, survivors should undergo careful breast cancer surveillance, including annual mammography and breast self-exam...

  2. Breast asymmetry and predisposition to breast cancer

    OpenAIRE

    Scutt, Diane; Lancaster, Gillian A; Manning, John T

    2006-01-01

    INTRODUCTION: It has been shown in our previous work that breast asymmetry is related to several of the known risk factors for breast cancer, and that patients with diagnosed breast cancer have more breast volume asymmetry, as measured from mammograms, than age-matched healthy women. METHODS: In the present study, we compared the breast asymmetry of women who were free of breast disease at time of mammography, but who had subsequently developed breast cancer, with that of age-matched healthy ...

  3. Loss of PTEN expression is associated with aggressive behavior and poor prognosis in Middle Eastern triple-negative breast cancer.

    Science.gov (United States)

    Beg, Shaham; Siraj, Abdul K; Prabhakaran, Sarita; Jehan, Zeenath; Ajarim, Dahish; Al-Dayel, Fouad; Tulbah, Asma; Al-Kuraya, Khawla S

    2015-06-01

    PTEN is a tumor suppressor that negatively regulates the PI3 K-AKT signaling pathway which is involved in the pathogenesis of many different tumor types and serves as a prognostic marker in breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic breast cancer has not been explored especially with the fact that breast cancer originating from this ethnic population tend to behave more aggressively than breast cancer in the west. In this study, we analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast cancers with clinical follow-up data. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN immunostaining was observed in 77 % of the cases. PTEN loss was significantly associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor recurrence (p = 0.0333), and triple-negative breast cancers (p = 0.0086). PTEN loss in triple-negative breast cancers was significantly associated with rapid tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4 %). Loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as potential therapeutic target in triple-negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of breast cancer.

  4. Relationship of Predicted Risk of Developing Invasive Breast Cancer, as Assessed with Three Models, and Breast Cancer Mortality among Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Mark E Sherman

    Full Text Available Breast cancer risk prediction models are used to plan clinical trials and counsel women; however, relationships of predicted risks of breast cancer incidence and prognosis after breast cancer diagnosis are unknown.Using largely pre-diagnostic information from the Breast Cancer Surveillance Consortium (BCSC for 37,939 invasive breast cancers (1996-2007, we estimated 5-year breast cancer risk (<1%; 1-1.66%; ≥1.67% with three models: BCSC 1-year risk model (BCSC-1; adapted to 5-year predictions; Breast Cancer Risk Assessment Tool (BCRAT; and BCSC 5-year risk model (BCSC-5. Breast cancer-specific mortality post-diagnosis (range: 1-13 years; median: 5.4-5.6 years was related to predicted risk of developing breast cancer using unadjusted Cox proportional hazards models, and in age-stratified (35-44; 45-54; 55-69; 70-89 years models adjusted for continuous age, BCSC registry, calendar period, income, mode of presentation, stage and treatment. Mean age at diagnosis was 60 years.Of 6,021 deaths, 2,993 (49.7% were ascribed to breast cancer. In unadjusted case-only analyses, predicted breast cancer risk ≥1.67% versus <1.0% was associated with lower risk of breast cancer death; BCSC-1: hazard ratio (HR = 0.82 (95% CI = 0.75-0.90; BCRAT: HR = 0.72 (95% CI = 0.65-0.81 and BCSC-5: HR = 0.84 (95% CI = 0.75-0.94. Age-stratified, adjusted models showed similar, although mostly non-significant HRs. Among women ages 55-69 years, HRs approximated 1.0. Generally, higher predicted risk was inversely related to percentages of cancers with unfavorable prognostic characteristics, especially among women 35-44 years.Among cases assessed with three models, higher predicted risk of developing breast cancer was not associated with greater risk of breast cancer death; thus, these models would have limited utility in planning studies to evaluate breast cancer mortality reduction strategies. Further, when offering women counseling, it may be useful to note that high

  5. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    International Nuclear Information System (INIS)

    Chen, Yi; Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi; Jing, Qian; Yue, Jiaqi; Liu, Yang; Cheng, Zhong; Li, Jingyi; Song, Haixing; Li, Guoyu; Liu, Rui; Wang, Jinhui

    2016-01-01

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  6. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Jing, Qian; Yue, Jiaqi; Liu, Yang [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Cheng, Zhong [Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Li, Jingyi, E-mail: li--jingyi@hotmail.com [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Song, Haixing [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Li, Guoyu, E-mail: liguoyulisa@163.com [School of Pharmacy, Shihezi University, Shihezi 832003 (China); Liu, Rui, E-mail: liurui_scu@hotmail.com [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Wang, Jinhui [School of Pharmacy, Shihezi University, Shihezi 832003 (China)

    2016-05-20

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  7. A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Christina Marie Gutierrez

    2015-11-01

    Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.

  8. FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition.

    Science.gov (United States)

    Ogunbolude, Yetunde; Dai, Chenlu; Bagu, Edward T; Goel, Raghuveera Kumar; Miah, Sayem; MacAusland-Berg, Joshua; Ng, Chi Ying; Chibbar, Rajni; Napper, Scott; Raptis, Leda; Vizeacoumar, Frederick; Vizeacoumar, Franco; Bonham, Keith; Lukong, Kiven Erique

    2017-12-22

    The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells. Finally, we interrogated the TCGA and GENT gene expression databases to determine the correlation between the expression of FRK and epithelial/mesenchymal markers. We observed that FRK overexpression suppressed cell proliferation, migration, and invasiveness, inhibited various JAK/STAT, MAPK and Akt signaling pathways, and suppressed the expression of some STAT3 target genes. Also, FRK overexpression increased the expression of epithelial markers including E-cadherin mRNA and down-regulated the transcript levels of vimentin, fibronectin, and slug. Finally, we observed an inverse correlation between FRK expression and mesenchymal markers in a large cohort of breast cancer cells. Our data, therefore, suggests that FRK represses cell proliferation, migration and invasiveness by suppressing epithelial to mesenchymal transition.

  9. Nuclear osteopontin-c is a prognostic breast cancer marker.

    Science.gov (United States)

    Zduniak, K; Ziolkowski, P; Ahlin, C; Agrawal, A; Agrawal, S; Blomqvist, C; Fjällskog, M-L; Weber, G F

    2015-02-17

    Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis.

  10. The Effect of Breast Cancer Fatalism on Breast Cancer Awareness Among Turkish Women.

    Science.gov (United States)

    Altintas, Hulya Kulakci; Ayyildiz, Tulay Kuzlu; Veren, Funda; Topan, Aysel Kose

    2017-10-01

    The aim of this study was to evaluate the effect of breast cancer fatalism and other factors on breast cancer awareness among Turkish women. This cross-sectional and comparative descriptive study was conducted with 894 women. Data were collected by Personal Information Form, Powe Fatalism Inventory and Champion's Health Belief Model Scale. Seriousness, health motivation, BSE benefits and BSE self-efficacy perceptions of the women were moderate, and susceptibility and BSE barriers perceptions were low. It was determined that awareness of breast cancer of the women was affected by breast cancer fatalism, age, education level, employment status, marital status, family type, economic status, social assurance, menopause status, family history of cancer, family history of breast cancer, knowledge on BSE, source of information on BSE, performing of BSE, frequency of BSE performing, having a problem with breast, having a breast examination in hospital, feeling during breast examination by healthcare professional, sex of healthcare professional for breast examination and their health beliefs (p breast cancer of the women was affected by breast cancer fatalism. In providing breast cancer early diagnosis behaviors, it is recommended to evaluate fatalism perceptions and health beliefs of the women and to arrange educational programs for this purpose.

  11. Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica).

    Science.gov (United States)

    Weil, Marvin J; Zhang, Yanjun; Nair, Muraleedharan G

    2004-01-01

    A reduced incidence of different types of cancer has been linked to consumption of Brassica vegetables, and there is evidence that glucosinolates (GSLs) and their hydrolysis products play a role in reducing cancer risk. Wasabi (Wasabia japonica) and horseradish (Armoracia rusticana), both Brassica vegetables, are widely used condiments both in Japanese cuisine and in the United States. Desulfosinigrin (DSS) (1) was isolated from a commercially available wasabi powder and from fresh wasabi roots. Sinigrin (2) was isolated from horseradish roots. DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, on lipid peroxidation, and on the proliferation of human colon (HCT-116), breast (MCF-7), lung (NCIH460), and central nervous system (CNS, SF-268) cancer cell lines. DSS did not inhibit COX enzymes or lipid peroxidation at 250 microg/ml. Sinigrin inhibited lipid peroxidation by 71% at 250 microg/ml. However, DSS promoted the growth of HCT-116 (colon) and NCI H460 (lung) human cancer cells as determined by the MTT assay in a concentration-dependent manner. At 3.72 microg/ml, a 27% increase in the number of viable human HCT-116 colon cancer cells was observed; the corresponding increases at 7.50 and 15 microg/ml were 42 and 69%, respectively. At 60 microg/ml, DSS doubled the number of HCT-16 colon cancer cells. For NCI H460 human lung cancer cells, DSS at 60 microg/ml increased the cell number by 20%. Sinigrin showed no proliferating effect on the tumor cells tested. This is the first report of the tumor cell-proliferating activity by a desulfoglucosinolate, the biosynthetic precursor of GSLs found in Brassica spp.

  12. Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

    Science.gov (United States)

    Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

    2016-01-01

    Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment.

  13. Breast cancer in men

    Science.gov (United States)

    ... in situ - male; Intraductal carcinoma - male; Inflammatory breast cancer - male; Paget disease of the nipple - male; Breast cancer - male ... The cause of breast cancer in men is not clear. But there are risk factors that make breast cancer more likely in men: Exposure to ...

  14. Genetic variation in CYP19A1 and risk of breast cancer and fibrocystic breast conditions among women in Shanghai, China.

    Science.gov (United States)

    Chen, Chu; Sakoda, Lori C; Doherty, Jennifer A; Loomis, Melissa M; Fish, Sherianne; Ray, Roberta M; Lin, Ming Gang; Fan, Wenhong; Zhao, Lue Ping; Gao, Dao Li; Stalsberg, Helge; Feng, Ziding; Thomas, David B

    2008-12-01

    CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted.

  15. NF-kappa B genes have a major role in Inflammatory Breast Cancer

    International Nuclear Information System (INIS)

    Lerebours, Florence; Vacher, Sophie; Andrieu, Catherine; Espie, Marc; Marty, Michel; Lidereau, Rosette; Bieche, Ivan

    2008-01-01

    IBC (Inflammatory Breast cancer) is a rare form of breast cancer with a particular phenotype. New molecular targets are needed to improve the treatment of this rapidly fatal disease. Given the role of NF-κB-related genes in cell proliferation, invasiveness, angiogenesis and inflammation, we postulated that they might be deregulated in IBC. We measured the mRNA expression levels of 60 NF-κB-related genes by using real-time quantitative RT-PCR in a well-defined series of 35 IBCs, by comparison with 22 stage IIB and III non inflammatory breast cancers. Twenty-four distant metastases of breast cancer served as 'poor prognosis' breast tumor controls. Thirty-five (58%) of the 60 NF-κB-related genes were significantly upregulated in IBC compared with non IBC. The upregulated genes were NF-κB genes (NFKB1, RELA, IKBKG, NFKBIB, NFKB2, REL, CHUK), apoptosis genes (MCL1L, TNFAIP3/A20, GADD45B, FASLG, MCL1S, IER3L, TNFRSF10B/TRAILR2), immune response genes (CD40, CD48, TNFSF11/RANKL, TNFRSF11A/RANK, CCL2/MCP-1, CD40LG, IL15, GBP1), proliferation genes (CCND2, CCND3, CSF1R, CSF1, SOD2), tumor-promoting genes (CXCL12, SELE, TNC, VCAM1, ICAM1, PLAU/UPA) or angiogenesis genes (PTGS2/COX2, CXCL1/GRO1). Only two of these 35 genes (PTGS2/COX2 and CXCL1/GRO1)were also upregulated in breast cancer metastases. We identified a five-gene molecular signature that matched patient outcomes, consisting of IL8 and VEGF plus three NF-κB-unrelated genes that we had previously identified as prognostic markers in the same series of IBC. The NF-κB pathway appears to play a major role in IBC, possibly contributing to the unusual phenotype and aggressiveness of this form of breast cancer. Some upregulated NF-κB-related genes might serve as novel therapeutic targets in IBC

  16. Immunohistochemical Expression of Survivin in Breast Carcinoma: Relationship with Clinico pathological Parameters, Proliferation and Molecular Classification

    International Nuclear Information System (INIS)

    YOUSSEF, N.S.; HEWEDI, I.H.; ABD RABOH, N.M.

    2008-01-01

    Background and Objective: Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with more aggressive behavior and parameters of poor prognosis in most human cancers including gastric, colorectal and bladder carcinomas. However, conflicting data exist on its prognostic effect in breast cancer. This current study is designed to assess survivin expression in breast carcinoma relating results with clinico pathological parameters, proliferation (MIB-1) and molecular classification. Material and Methods: Our retrospective study com- prised of 65 archived cases of breast carcinoma. Samples from the tumor and the adjacent normal breast tissue were immuno stained for survivin and MIB-1. Nuclear and cytoplasmic survivin expression was evaluated in normal breast tissue and carcinoma regarding both the intensity and the percentage of positive cells. ER, PR, HER2 were used as surrogate markers to classify the cases into four molecular subtypes. Results: Survivin expression was detected in 78.5% of breast carcinomas. The adjacent normal breast tissue was immuno negative. Survivin expression showed significant association with increased tumor size ( p <0.0001), high histologic grade ( p =0.04), lymph node metastases ( p <0.001), advanced tumor stage ( p <0.0001), MIB-1 expression ( p =0.02), negative estrogen receptor status ( p =0.01) and negative progesterone receptor status ( p <0.0001). The subcellular localization of survivin significantly related to histologic grade, stage and lymph node involvement. The percentage of TNP (triple negative phenotype) and HER2+/ER-PR- tumors expressing survivin were significantly higher compared to the Luminal subtypes ( p =0.01). Conclusion: Survivin expression was associated with parameters of poor prognosis in breast cancer. Moreover, the cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a potential target for novel

  17. Identification of the Mislabeled Breast Cancer Samples by Mitochondrial DNA Haplotyping

    Directory of Open Access Journals (Sweden)

    Xiaogang Chen

    2015-01-01

    Full Text Available The task to identify whether an archival malignant tumor specimen had been mislabeled or interchanged is a challenging one for forensic genetics. The nuclear DNA (nDNA markers were affected by the aberration of tumor cells, so they were not suitable for personal identification when the tumor tissues were tested. In this study, we focused on a new solution - mitochondrial single nucleotide polymorphism (mtSNP haplotyping by a multiplex SNaPshot assay. To validate our strategy of haplotyping with 25 mtSNPs, we analyzed 15 pairs of cancerous/healthy tissues taken from patients with ductal breast carcinoma. The haplotypes of all the fifteen breast cancer tissues were matched with their paired breast tissues. The heteroplasmy at 2 sites, 14783A/G and 16519C/T was observed in one breast tissue, which indicated a mixture of related mitochondrial haplotypes. However, only one haplotype was retained in the paired breast cancer tissue, which could be considered the result of proliferation of tumor subclone. The allele drop-out and allele drop-in were observed when 39 STRs and 20 tri-allelic SNPs of nDNA were applied. Compared to nDNA markers applied, 25 mtSNPs were more stable without interference from aberrance of breast cancer. Also, two cases were presented where the investigation of haplotype with 25 mtSNPs was used to prove the origin of biopsy specimen with breast cancer. The mislabeling of biopsy specimen with breast cancer could be certified in one case but could not be supported in the other case. We highlight the importance of stability of mtSNP haplotype in breast cancer. It was implied that our multiplex SNaPshot assay with 25 mtSNPs was a useful strategy to identify mislabeled breast cancer specimen.

  18. The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma

    Directory of Open Access Journals (Sweden)

    Kerry J. Davies

    2014-01-01

    Full Text Available Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise.

  19. BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression.

    Science.gov (United States)

    Ren, Wei; Sun, Xiaoxiao; Wang, Ke; Feng, Honglei; Liu, Yuehong; Fei, Chang; Wan, Shaoheng; Wang, Wei; Luo, Jinyong; Shi, Qiong; Tang, Min; Zuo, Guowei; Weng, Yaguang; He, Tongchuan; Zhang, Yan

    2014-03-01

    Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease.

  20. Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells

    OpenAIRE

    Fang, Feng; Zheng, Jiamao; Galbaugh, Traci L; Fiorillo, Alyson A; Hjort, Elizabeth E; Zeng, Xianke; Clevenger, Charles V

    2010-01-01

    The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB...

  1. Plasma membrane proteomics of human breast cancer cell lines identifies potential targets for breast cancer diagnosis and treatment.

    Directory of Open Access Journals (Sweden)

    Yvonne S Ziegler

    Full Text Available The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

  2. Gemcitabine resistance in breast cancer cells regulated by PI3K/AKT-mediated cellular proliferation exerts negative feedback via the MEK/MAPK and mTOR pathways

    Directory of Open Access Journals (Sweden)

    Yang XL

    2014-06-01

    ability of 231/Gem cells. Western blot analysis showed that treatment with a PI3K/AKT inhibitor decreased the expression levels of p-AKT, p-MEK, p-mTOR, and p-P70S6K; however, treatments with either MEK/MAPK or mTOR inhibitor significantly increased p-AKT expression. Thus, our data suggest that gemcitabine resistance in breast cancer cells is mainly mediated by activation of the PI3K/AKT signaling pathway. This occurs through elevated expression of p-AKT protein to promote cell proliferation and is negatively regulated by the MEK/MAPK and mTOR pathways. Keywords: chemoresistance, gemcitabine, breast cancer

  3. Breast MRI in pregnancy-associated breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Shin Jung; Shin, Sang Soo [Dept. of of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Lim, Hyo Soon; Baek, Jang Mi; Seon, Hyun Ju; Heo, Suk Hee; Kim, Jin Woong; Park, Min Ho [Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)

    2017-03-15

    The purpose of this study was to evaluate the usefulness of MR imaging and to describe the MR imaging findings of pregnancy-associated breast cancer. From 2006 to 2013, MR images of 23 patients with pregnancy-associated breast cancer were retrospectively evaluated. MR images were reviewed to evaluate lesion detection and imaging findings of pregnancy-associated breast cancer. MR images were analyzed by using the Breast Imaging Reporting and Data System and an additional MR-detected lesion with no mammographic or sonographic abnormality was determined. MR imaging depicted breast cancer in all patients, even in marked background parenchymal enhancement. Pregnancy-associated breast cancer was seen as a mass in 20 patients and as non-mass enhancement with segmental distribution in 3 patients. The most common features of the masses were irregular shape (85%), non-circumscribed margin (85%), and heterogeneous enhancement (60%). An additional site of cancer was detected with MR imaging in 5 patients (21.7%) and the type of surgery was changed. Pregnancy-associated breast cancer was usually seen as an irregular mass with heterogeneous enhancement on MR images. Although these findings were not specific, MR imaging was useful in evaluating the disease extent of pregnancy-associated breast cancer.

  4. Breast MRI in pregnancy-associated breast cancer

    International Nuclear Information System (INIS)

    Kim, Shin Jung; Shin, Sang Soo; Lim, Hyo Soon; Baek, Jang Mi; Seon, Hyun Ju; Heo, Suk Hee; Kim, Jin Woong; Park, Min Ho

    2017-01-01

    The purpose of this study was to evaluate the usefulness of MR imaging and to describe the MR imaging findings of pregnancy-associated breast cancer. From 2006 to 2013, MR images of 23 patients with pregnancy-associated breast cancer were retrospectively evaluated. MR images were reviewed to evaluate lesion detection and imaging findings of pregnancy-associated breast cancer. MR images were analyzed by using the Breast Imaging Reporting and Data System and an additional MR-detected lesion with no mammographic or sonographic abnormality was determined. MR imaging depicted breast cancer in all patients, even in marked background parenchymal enhancement. Pregnancy-associated breast cancer was seen as a mass in 20 patients and as non-mass enhancement with segmental distribution in 3 patients. The most common features of the masses were irregular shape (85%), non-circumscribed margin (85%), and heterogeneous enhancement (60%). An additional site of cancer was detected with MR imaging in 5 patients (21.7%) and the type of surgery was changed. Pregnancy-associated breast cancer was usually seen as an irregular mass with heterogeneous enhancement on MR images. Although these findings were not specific, MR imaging was useful in evaluating the disease extent of pregnancy-associated breast cancer

  5. Critical role of CDK11p58 in human breast cancer growth and angiogenesis

    International Nuclear Information System (INIS)

    Chi, Yayun; Huang, Sheng; Peng, Haojie; Liu, Mengying; Zhao, Jun; Shao, Zhiming; Wu, Jiong

    2015-01-01

    A capillary network is needed in cancer growth and metastasis. Induction of angiogenesis represents one of the major hallmarks of cancer. CDK11 p58 , a Ser/Thr kinase that belongs to the Cell Division Cycle 2-like 1 (CDC2L1) subfamily is associated with cell cycle progression, tumorigenesis, sister chromatid cohesion and apoptotic signaling. However, its role in breast cancer proliferation and angiogenesis remains unclear. Tumorigenicity assays and blood vessel assessment in athymic mice were used to assess the function of CDK11 p58 in tumor proliferation and angiogenesis. CCK-8 assay was used to detect breast cancer cell growth. Immunohistochemistry was used to detect the expression of vascular endothelial growth factor (VEGF), CD31 and CD34 in CDK11 positive patient breast cancer tissues. Dual-Luciferase array was used to analyze the function of CDK11 p58 in the regulation of VEGF promoter activity. Western blot was used to detect related protein expression levels. CDK11 p58 inhibited breast cancer growth and angiogenesis in breast cancer cells and in nude mice transplanted with tumors. Immunohistochemistry confirmed that CDK11 p58 was negatively associated with angiogenesis-related proteins such as VEGF, CD31 and CD34 in breast cancer patients. Real-time PCR and dual-luciferase assay showed CDK11 p58 inhibited the mRNA levels of VEGF and the promoter activity of VEGF. As CDK11 p58 is a Ser/Thr kinase, the kinase-dead mutant failed to inhibit VEGF mRNA and promoter activity. Western blot analysis showed the same pattern of related protein expression. The data suggested angiogenesis inhibition was dependent on CDK11 p58 kinase activity. This study indicates that CDK11 p58 inhibits the growth and angiogenesis of breast cancer dependent on its kinase activity. The online version of this article (doi:10.1186/s12885-015-1698-7) contains supplementary material, which is available to authorized users

  6. Breast cancer prevention.

    Science.gov (United States)

    Euhus, David M; Diaz, Jennifer

    2015-01-01

    Breast cancer is the most common cancer in women with 232,670 new cases estimated in the USA for 2014. Approaches for reducing breast cancer risk include lifestyle modification, chemoprevention, and prophylactic surgery. Lifestyle modification has a variety of health benefits with few associated risks and is appropriate for all women regardless of breast cancer risk. Chemoprevention options have expanded rapidly, but most are directed at estrogen receptor positive breast cancer and uptake is low. Prophylactic surgery introduces significant additional risks of its own and is generally reserved for the highest risk women. © 2014 Wiley Periodicals, Inc.

  7. 4-tert-Octylphenol stimulates the expression of cathepsins in human breast cancer cells and xenografted breast tumors of a mouse model via an estrogen receptor-mediated signaling pathway

    International Nuclear Information System (INIS)

    Lee, Hye-Rim; Choi, Kyung-Chul

    2013-01-01

    Highlights: ► Cathepsins B and D were markedly enhanced by octylphenol (OP) in MCF-7 cells. ► OP may accelerate breast cancer cell growth and cathepsins via ER-mediated signaling. ► Breast cancer cells exposed with OP to mouse model were more aggressive. ► OP can promote metastasis through the amplification of cathepsins B and D via ER-mediated signaling pathway. -- Abstract: Endocrine disrupting chemicals (EDCs) are defined as environmental compounds that modulate steroid hormone receptor-dependent responses an abnormal manner, resulting in adverse health problems for humans such as cancer growth and metastasis. Cathepsins are proteases that have been implicated in cancer progression. However, there have been few studies about the association between cathepsins and estrogenic chemicals during the cancer progression. In this study, we examined the effect(s) of 4-tert-octylphenol (OP), a potent EDC, on the expression of cathepsins B and D in human MCF-7 breast cancer cells and a xenograft mouse model. Treatment with OP significantly induced the proliferation MCF-7 cells in an MTT assay. In addition, the expression of cathepsins B and D was markedly enhanced in MCF-7 cells at both the transcriptional and the translational levels following treatment with E2 or OP up to 48 h. These results demonstrated the ability of OP to disrupt normal transcriptional regulation of cathepsins B and D in human breast cancer cells. However, the effects of OP on cell growth or overexpression of cathepsins by inhibiting ER-mediated signaling were abolished by an ER antagonist and siRNA specific for ERα. In conclusion, our findings suggest that OP at 10 −6 M, like E2, may accelerate breast cancer cell proliferation and the expression of cathepsins through an ER-mediated signaling pathway. In addition, the breast cancer cells exposed with OP to a xenograft mouse model were more aggressive according to our histological analysis and showed markedly increased expression of

  8. Can vitamin A modify the activity of docetaxel in MCF-7 breast cancer cells?

    Directory of Open Access Journals (Sweden)

    Dorota Lemancewicz

    2008-04-01

    Full Text Available Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. On the other hand, the vitamin A family compounds play the essential roles in many biological processes in mammary gland. The aim of our study was to investigate the effect of all-trans retinol, carotenoids (beta-carotene, lycopene and retinoids (9-cis, 13-cis and all-trans retinoic acid on the activity of docetaxel and to compare these effects with the estradiol and tamoxifen actions on human ER(+ MCF-7 breast cancer cell line. The evaluation was based on [3H] thymidine incorporation and the proliferative activity of PCNA and Ki 67 positive cells. In our study, the incorporation of [3H] thymidine into cancer cells was inhibited to 50% by 0.2, 0.5 and 1 microM of docetaxel in the 24-hour culture and addition of estradiol (0.001 microM didn't influence the results. However, addition of tamoxifen caused a statistically significant decrease of the percentage of the proliferating cells in the culture medium with 0.2 and 0.5 microM of docetaxel (38.99 +/- 2.84%, p<0.01 and 40.67 +/- 5.62%, p<0.01 in comparison to the docetaxel only group. The above-mentioned observations were also confirmed with the use of the immunohistochemical investigations. Among the examined vitamin A family compounds, the simultaneous application of beta-carotene (0.1 microM and docetaxel (0.2 microM resulted in a statistically significant reduction in the percentage of proliferating cells (40.25 +/- 14.62%, p<0.01. Lycopene (0.1 microM, which stimulates the growth of breast cancer cells in a 24-hour culture, had an inhibitory effect (42.97 +/- 9.58%, p<0.01 when combined with docetaxel (0.2 microM. Although, beta-carotene and lycopene belong to the different chemical groups, they surprisingly had a similar inhibitory influence on both growth and proliferation of MCF-7 breast cancer cells when combined with docetaxel. The application of docetaxel either with beta-carotene or

  9. Estrogen receptor-α36 is involved in pterostilbene-induced apoptosis and anti-proliferation in in vitro and in vivo breast cancer.

    Directory of Open Access Journals (Sweden)

    Chi Pan

    Full Text Available Pterostilbene (trans-3,5-dimethoxy-4'-hudroxystilbene is an antioxidant primarily found in blueberries. It also inhibits breast cancer regardless of conventional estrogen receptor (ER-α66 status by inducing both caspase-dependent and caspase-independent apoptosis. However, the pterostilbene-induced apoptosis rate in ER-α66-negative breast cancer cells is much higher than that in ER-α66-positive breast cancer cells. ER-α36, a variant of ER-α66, is widely expressed in ER-α66-negative breast cancer, and its high expression mediates the resistance of ER-α66-positive breast cancer patients to tamoxifen therapy. The aim of the present study is to determine the relationship between the antiproliferation activity of pterostilbene and ER-α36 expression in breast cancer cells. Methyl-thiazolyl-tetrazolium (MTT assay, apoptosis analysis, and an orthotropic xenograft mouse model were used to examine the effects of pterostilbene on breast cancer cells. The expressions of ER-α36 and caspase 3, the activation of ERK and Akt were also studied through RT-PCR, western blot analysis, and immunohistochemical (IHC staining. ER-α36 knockdown was found to desensitize ER-α66-negative breast cancer cells to pterostilbene treatment both in vitro and in vivo, and high ER-α36 expression promotes pterostilbene-induced apoptosis in breast cancer cells. Western blot analysis data indicate that MAPK/ERK and PI3K/Akt signaling in breast cancer cells with high ER-α36 expression are mediated by ER-α36, and are inhibited by pterostilbene. These results suggest that ER-α36 is a therapeutic target in ER-α36-positive breast cancer, and pterostilbene is an inhibitor that targets ER-α36 in the personalized therapy against ER-α36-positive breast cancer.

  10. Breast cancer

    OpenAIRE

    Gablerová, Pavlína

    2010-01-01

    In this work the topic of breast cancer treated more generally and mainly focused on risk factors for the development. The theoretical part describes the general knowledge about breast cancer as a stage or treatment. The practical part is to have clarified the risk factors that have some bearing on the diagnosis of breast cancer. What level are involved in the probability of occurrence? Can we eliminate them? As a comparison of risk factors examined in the Czech Republic, England, Australia a...

  11. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

    2014-06-13

    Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.

  12. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

    International Nuclear Information System (INIS)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie

    2014-01-01

    Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor

  13. Targeting the S1P Axis and Development of a Novel Therapy for Obesity Related Triple Negative Breast Cancer

    Science.gov (United States)

    2017-09-01

    with the options ‘intersection-nonempty’ mode, non- stranded , minimum quality 10, and ‘exon’ was used as the feature type, with ‘gene_id’ as the GTF...Keywords: sphingosine-1-phosphate, sphingosine kinase, estradiol, breast cancer, FTY720/fingolimod. Abbreviations: BCSCs, breast cancer stem cells; ,ER...pathway along with p38MAPK in breast cancer stem cells (BCSCs) leading to proliferation and tumorigenicity (Hirata et al., 2014). BCSCs can also be

  14. MFAP5 promotes tumor progression and bone metastasis by regulating ERK/MMP signaling pathways in breast cancer.

    Science.gov (United States)

    Wu, Zhiqiang; Wang, Ting; Fang, Meng; Huang, Wending; Sun, Zhengwang; Xiao, Jianru; Yan, Wangjun

    2018-04-06

    Breast cancer accounts for about 30% of all cancers in women, while approximately 70% breast cancer patients developed bone metastases throughout the course of their disease, highlighting the importance of exploring new therapeutic targets. Microfibrillar-associated protein 5 (MFAP5) is a component of extracellular elastic microfibril which has been confirmed to function in tissue development and cancer progression. But the role of MFAP5 in breast cancer remains unclear. The present study demonstrated that MFAP5 was up-regulated in breast cancers compared with that in normal breast tissues, and further increased in breast cancer bone metastasis. Functionally, MFAP5 overexpression accelerated breast cancer cell proliferation and migration, while an opposite effect was observed when MFAP5 was knocked down. In addition, up-regulation of MFAP5 increased the expression of MMP2 and MMP9 and activated the ERK signaling pathway. Conversely, inhibition of MFAP5 suppressed the expression of MMP2, MMP9, p-FAK, p-Erk1/2 and p-cJun. These findings may provide a better understanding about the mechanism of breast cancer and suggest that MFAP5 may be a potential prognostic biomarker and therapeutic target for breast cancer, especially for bone metastasis of breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Structure-based pharmacophore design and virtual screening for novel potential inhibitors of epidermal growth factor receptor as an approach to breast cancer chemotherapy.

    Science.gov (United States)

    Mahernia, Shabnam; Hassanzadeh, Malihe; Sharifi, Niusha; Mehravi, Bita; Paytam, Fariba; Adib, Mehdi; Amanlou, Massoud

    2018-02-01

    Cancer cells are described with features of uncontrolled growth, invasion and metastasis. The epidermal growth factor receptor subfamily of tyrosine kinases (EGFR-TK) plays a crucial regulatory role in the control of cellular proliferation and progression of various cancers. Therefore, its inhibition might lead to the discovery of a new generation of anticancer drugs. In the present study, structure-based pharmacophore modeling, molecular docking and molecular dynamics simulations were applied to identify potential hits, which exhibited good inhibition on the proliferation of MCF-7 breast cancer cell line and favorable binding interactions on EGFR-TK. Selected compounds were examined for their anticancer activity against the Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line which overexpresses EGFR using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay. Compounds 1 and 2, with an isoindoline-1-one core, induced significant inhibition of breast cancer cells proliferation with IC[Formula: see text] values 327 and 370 nM, respectively.

  16. Tetrandrine, a Compound Common in Chinese Traditional Medicine, Preferentially Kills Breast Cancer Tumor Initiating Cells (TICs) In Vitro

    International Nuclear Information System (INIS)

    Xu, Wei; Debeb, Bisrat G.; Lacerda, Lara; Li, Jessica; Woodward, Wendy A.

    2011-01-01

    Tetrandrine is a bisbenzylisoquinoline alkaloid found in Stephania tetrandra, a Chinese medicine commonly used as an anti-inflammatory. It has extensive pharmacological activity, including positive ion channel blockade and inhibition of multiple drug resistance proteins. These activities are very similar to that of salinomycin, a known drug targeting breast cancer initiation cells (TICs). Herein, we tested tetrandrine targeting of breast cancer TICs. SUM-149, an inflammatory breast cancer cell line and SUM-159, a non-inflammatory metaplastic breast cancer cell line were used in these studies. In proliferation assays using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium (MTS), we found that the IC 50 for inhibition of proliferation is 15.3 ± 4.1 μM for SUM-149 and 24.3 ± 2.1 μM for SUM-159 cells. Tetrandrine also inhibited mammosphere formation, a surrogate for breast cancer TICs growth in vitro with IC 50 around 1 μM for SUM-149 and around 2 μM for SUM-159 cells. Tetrandrine has similar effects on the mammosphere formation from cells isolated from fresh patient sample. Moreover, tetrandrine decreases the aldehyde dehydrogenase (ALDH) positive population in SUM-159 by 45% ± 5.45% P = 0.005. In summary, tetrandrine demonstrates significant efficacy against in vitro surrogates for inflammatory and aggressive breast cancer TICs

  17. Tetrandrine, a Compound Common in Chinese Traditional Medicine, Preferentially Kills Breast Cancer Tumor Initiating Cells (TICs) In Vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Wei; Debeb, Bisrat G.; Lacerda, Lara; Li, Jessica; Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Division of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States)

    2011-05-04

    Tetrandrine is a bisbenzylisoquinoline alkaloid found in Stephania tetrandra, a Chinese medicine commonly used as an anti-inflammatory. It has extensive pharmacological activity, including positive ion channel blockade and inhibition of multiple drug resistance proteins. These activities are very similar to that of salinomycin, a known drug targeting breast cancer initiation cells (TICs). Herein, we tested tetrandrine targeting of breast cancer TICs. SUM-149, an inflammatory breast cancer cell line and SUM-159, a non-inflammatory metaplastic breast cancer cell line were used in these studies. In proliferation assays using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium (MTS), we found that the IC{sub 50} for inhibition of proliferation is 15.3 ± 4.1 μM for SUM-149 and 24.3 ± 2.1 μM for SUM-159 cells. Tetrandrine also inhibited mammosphere formation, a surrogate for breast cancer TICs growth in vitro with IC{sub 50} around 1 μM for SUM-149 and around 2 μM for SUM-159 cells. Tetrandrine has similar effects on the mammosphere formation from cells isolated from fresh patient sample. Moreover, tetrandrine decreases the aldehyde dehydrogenase (ALDH) positive population in SUM-159 by 45% ± 5.45% P = 0.005. In summary, tetrandrine demonstrates significant efficacy against in vitro surrogates for inflammatory and aggressive breast cancer TICs.

  18. Tetrandrine, a Compound Common in Chinese Traditional Medicine, Preferentially Kills Breast Cancer Tumor Initiating Cells (TICs In Vitro

    Directory of Open Access Journals (Sweden)

    Jessica Li

    2011-05-01

    Full Text Available Tetrandrine is a bisbenzylisoquinoline alkaloid found in Stephania tetrandra, a Chinese medicine commonly used as an anti-inflammatory. It has extensive pharmacological activity, including positive ion channel blockade and inhibition of multiple drug resistance proteins. These activities are very similar to that of salinomycin, a known drug targeting breast cancer initiation cells (TICs. Herein, we tested tetrandrine targeting of breast cancer TICs. SUM-149, an inflammatory breast cancer cell line and SUM-159, a non-inflammatory metaplastic breast cancer cell line were used in these studies. In proliferation assays using 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS, we found that the IC50 for inhibition of proliferation is 15.3 ± 4.1 µM for SUM-149 and 24.3 ± 2.1 µM for SUM-159 cells. Tetrandrine also inhibited mammosphere formation, a surrogate for breast cancer TICs growth in vitro with IC50 around 1 µM for SUM-149 and around 2 µM for SUM-159 cells. Tetrandrine has similar effects on the mammosphere formation from cells isolated from fresh patient sample. Moreover, tetrandrine decreases the aldehyde dehydrogenase (ALDH positive population in SUM-159 by 45% ± 5.45% P = 0.005. In summary, tetrandrine demonstrates significant efficacy against in vitro surrogates for inflammatory and aggressive breast cancer TICs.

  19. Cyclooxygenase-2 inhibitor induces apoptosis in breast cancer cells in an in vivo model of spontaneous metastatic breast cancer.

    Science.gov (United States)

    Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Lagioia, Michelle; Gendler, Sandra J; Mukherjee, Pinku

    2004-11-01

    Cyclooxygenase-2 (COX-2) inhibitors are rapidly emerging as a new generation of therapeutic drug in combination with chemotherapy or radiation therapy for the treatment of cancer. The mechanisms underlying its antitumor effects are not fully understood and more thorough preclinical trials are needed to determine if COX-2 inhibition represents a useful approach for prevention and/or treatment of breast cancer. The purpose of this study was to evaluate the growth inhibitory mechanism of a highly selective COX-2 inhibitor, celecoxib, in an in vivo oncogenic mouse model of spontaneous breast cancer that resembles human disease. The oncogenic mice carry the polyoma middle T antigen driven by the mouse mammary tumor virus promoter and develop primary adenocarcinomas of the breast. Results show that oral administration of celecoxib caused significant reduction in mammary tumor burden associated with increased tumor cell apoptosis and decreased proliferation in vivo. In vivo apoptosis correlated with significant decrease in activation of protein kinase B/Akt, a cell survival signaling kinase, with increased expression of the proapoptotic protein Bax and decreased expression of the antiapoptotic protein Bcl-2. In addition, celecoxib treatment reduced levels of proangiogenic factor (vascular endothelial growth factor), suggesting a role of celecoxib in suppression of angiogenesis in this model. Results from these preclinical studies will form the basis for assessing the feasibility of celecoxib therapy alone or in combination with conventional therapies for treatment and/or prevention of breast cancer.

  20. miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer

    Science.gov (United States)

    Tan, Xiaohui; Fu, Yebo; Chen, Liang; Lee, Woojin; Lai, Yinglei; Rezaei, Katayoon; Tabbara, Sana; Latham, Patricia; Teal, Christine B.; Man, Yan-Gao; Siegel, Robert S.; Brem, Rachel F.; Fu, Sidney W.

    2016-01-01

    MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. cDNA microarray data revealed that differentially expressed genes when miR-671-5p was transfected are associated with cell proliferation, invasion, cell cycle, and EMT. These data indicate that miR-671-5p functions as a tumor suppressor miRNA in breast cancer by directly targeting FOXM1. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management. PMID:26588055

  1. Prevention of breast cancer.

    Science.gov (United States)

    Olver, Ian N

    2016-11-21

    Modifiable lifestyle factors may reduce the risk of developing breast cancer. Obesity is associated particularly with post-menopausal breast cancer. Diet is important, and exercise equivalent to running for up to 8 hours each week reduces the risk of breast cancer, both in its own right and through reducing obesity. Alcohol consumption may be responsible for 5.8% of breast cancers in Australia and it is recommended to reduce this to two standard drinks per day. Drinking alcohol and smoking increases the risk for breast cancer and, therefore, it is important to quit tobacco smoking. Prolonged use of combined oestrogen and progesterone hormone replacement therapy and oral contraceptives may increase breast cancer risk and this must be factored into individual decisions about their use. Ionising radiation, either from diagnostic or therapeutic radiation or through occupational exposure, is associated with a high incidence of breast cancer and exposure may be reduced in some cases. Tamoxifen chemoprevention may reduce the incidence of oestrogen receptor positive cancer in 51% of women with high risk of breast cancer. Uncommon but serious side effects include thromboembolism and uterine cancer. Raloxifene, which can also reduce osteoporosis, can be used in post-menopausal women and is not associated with the development of uterine cancer. Surgical prophylaxis with bilateral mastectomy and salpingo-oophorectomy can reduce the risk of breast cancer in patients carrying BRCA1 or BRCA2 mutations. For preventive treatments, mammographic screening can identify other women at high risk.

  2. Human breast tissue disposition and bioactivity of limonene in women with early stage breast cancer

    Science.gov (United States)

    Miller, Jessica A.; Lang, Julie E.; Ley, Michele; Nagle, Ray; Hsu, Chiu-Hsieh; Thompson, Patricia A; Cordova, Catherine; Waer, Amy; Chow, H.-H. Sherry

    2013-01-01

    Limonene is a bioactive food component found in citrus peel oil that has demonstrated chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited forty-three women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for 2 – 6 weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean=41.3 μg/g tissue) while the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P=0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase 3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, IGFBP-3 and IL-6 levels were observed following limonene intervention. There was a small but statistically significant post-intervention increase in IGF-1 levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell cycle arrest and reduced cell proliferation. Further placebo-controlled clinical trials and translational research are warranted to establish limonene’s role for breast cancer prevention or treatment. PMID:23554130

  3. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer.

    Science.gov (United States)

    Miller, Jessica A; Lang, Julie E; Ley, Michele; Nagle, Ray; Hsu, Chiu-Hsieh; Thompson, Patricia A; Cordova, Catherine; Waer, Amy; Chow, H-H Sherry

    2013-06-01

    Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.

  4. Prognostic value of human apurinic/apyrimidinic endonuclease 1 (APE1 expression in breast cancer.

    Directory of Open Access Journals (Sweden)

    Joohyun Woo

    Full Text Available Human apurinic/apyrimidinic endonuclease 1 (APE1 is an essential protein for DNA base excision repair (BER and redox regulation. The ability of cancer cells to recognize DNA damage and initiate DNA repair is an important mechanism for therapeutic resistance. Several recent studies have suggested that APE1 expression levels and/or subcellular dysregulation may be used to indicate the sensitivity of tumors to radiotherapy or chemotherapy. In this study, we assessed the prognostic significance of APE1 and differences in APE1 expression levels according to breast cancer molecular subtypes. We analyzed formalin-fixed, paraffin-embedded tumor tissue sections from 243 cases diagnosed as invasive breast cancer at Ewha Womans University Medical Center between January 2003 and December 2008. Immunohistochemistry was performed and the nuclear level of APE1 was scored by taking into account the percentage of positive cells. Medical records were reviewed to investigate clinicopathologic characteristics. We found that nuclear APE1 high-level expression (proportion ≥50% in breast cancer showed a tendency towards unfavorable prognosis regarding disease-free survival (p = 0.093. However, there was no significant difference in overall survival between low and high-level expression groups (p = 0.294. Interestingly, within the Ki-67 low-level expression group, APE1 low-level expression was significantly associated with poor overall survival (p = 0.007. A significant positive correlation was observed between APE1 nuclear expression and estrogen receptor status (75.7% vs. 59.7%, p = 0.022. Also, the luminal A subtype was the most commonly observed breast cancer subtype in the APE1 high-level expression group (61.6% vs. 45.2%, p = 0.000. This study suggests that APE1 expression may be associated with breast cancer prognosis. In particular, its role as a prognostic factor would be significant for breast cancers with a low Ki-67 proliferation index

  5. Targeting Aberrant p70S6K Activation for Estrogen Receptor-Negative Breast Cancer Prevention.

    Science.gov (United States)

    Wang, Xiao; Yao, Jun; Wang, Jinyang; Zhang, Qingling; Brady, Samuel W; Arun, Banu; Seewaldt, Victoria L; Yu, Dihua

    2017-11-01

    The prevention of estrogen receptor-negative (ER-) breast cancer remains a major challenge in the cancer prevention field, although antiestrogen and aromatase inhibitors have shown adequate efficacy in preventing estrogen receptor-positive (ER + ) breast cancer. Lack of commonly expressed, druggable targets is a major obstacle for meeting this challenge. Previously, we detected the activation of Akt signaling pathway in atypical hyperplasic early-stage lesions of patients. In the current study, we found that Akt and the downstream 70 kDa ribosomal protein S6 kinase (p70S6K) signaling pathway was highly activated in ER - premalignant breast lesions and ER - breast cancer. In addition, p70S6K activation induced transformation of ER - human mammary epithelial cells (hMEC). Therefore, we explored the potential of targeting Akt/p70S6K in the p70S6K activated, ER - hMEC models and mouse mammary tumor models for the prevention of ER - breast cancer. We found that a clinically applicable Akt/p70S6K dual inhibitor, LY2780301, drastically decreased proliferation of hMECs with ErbB2-induced p70S6K activation via Cyclin B1 inhibition and cell-cycle blockade at G 0 -G 1 phase, while it did not significantly reverse the abnormal acinar morphology of these hMECs. In addition, a brief treatment of LY2780301 in MMTV- neu mice that developed atypical hyperplasia (ADH) and mammary intraepithelial neoplasia (MIN) lesions with activated p70S6K was sufficient to suppress S6 phosphorylation and decrease cell proliferation in hyperplasic MECs. In summary, targeting the aberrant Akt/p70S6K activation in ER - hMEC models in vitro and in the MMTV- neu transgenic mouse model in vivo effectively inhibited Akt/S6K signaling and reduced proliferation of hMECs in vitro and ADH/MIN lesions in vivo , indicating its potential in prevention of p70S6K activated ER - breast cancer. Cancer Prev Res; 10(11); 641-50. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Developing Breast Cancer Program at Xavier; Genomic and Proteomic Analysis of Signaling Pathways Involved in Xenohormone and MEK5 Regulation of Breast Cancer

    Science.gov (United States)

    2010-05-01

    Tagatose are rare. In this study we have determined the effect of these rare ketohexoses on breast cancer cell proliferation and estrogen signalling...Cancer Center (TCC) will build a core of human talent that will address scientific problems such as drug resistance and the effect of environmental agents...pathways for ER(+) (MCF-7) and ER(-) (MCF-7-MEK5) as potentially more effective therapeutic targets. 11 Abstract of RCMI proposal submitted to

  7. The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer

    International Nuclear Information System (INIS)

    Akkiprik, Mustafa; Hu, Limei; Sahin, Aysegul; Hao, Xishan; Zhang, Wei

    2009-01-01

    Insulin-like growth factor binding protein 5 (IGFBP5) has been shown to be associated with breast cancer metastasis in clinical marker studies. However, a major difficulty in understanding how IGFBP5 functions in this capacity is the paradoxical observation that ectopic overexpression of IGFBP5 in breast cancer cell lines results in suppressed cellular proliferation. In cancer tissues, IGFBP5 resides mainly in the cytoplasm; however, in transfected cells, IGFBP5 is mainly located in the nucleus. We hypothesized that subcellular localization of IGFBP5 affects its functions in host cells. To test this hypothesis, we generated wild-type and mutant IGFBP5 expression constructs. The mutation occurs within the nuclear localization sequence (NLS) of the protein and is generated by site-directed mutagenesis using the wild-type IGFBP5 expression construct as a template. Next, we transfected each expression construct into MDA-MB-435 breast cancer cells to establish stable clones overexpressing either wild-type or mutant IGFBP5. Functional analysis revealed that cells overexpressing wild-type IGFBP5 had significantly lower cell growth rate and motility than the vector-transfected cells, whereas cells overexpressing mutant IGFBP5 demonstrated a significantly higher ability to proliferate and migrate. To illustrate the subcellular localization of the proteins, we generated wild-type and mutant IGFBP5-pDsRed fluorescence fusion constructs. Fluorescence microscopy imaging revealed that mutation of the NLS in IGFBP5 switched the accumulation of IGFBP5 from the nucleus to the cytoplasm of the protein. Together, these findings imply that the mutant form of IGFBP5 increases proliferation and motility of breast cancer cells and that mutation of the NLS in IGFBP5 results in localization of IGFBP5 in the cytoplasm, suggesting that subcellular localization of IGFBP5 affects its cell growth and migration functions in the breast cancer cells

  8. Stages of Male Breast Cancer

    Science.gov (United States)

    ... Breast & Gynecologic Cancers Breast Cancer Screening Research Male Breast Cancer Treatment (PDQ®)–Patient Version General Information about Male Breast Cancer Go to Health Professional Version Key Points Male ...

  9. RGS16 inhibits breast cancer cell growth by mitigating phosphatidylinositol 3-kinase signaling.

    Science.gov (United States)

    Liang, Genqing; Bansal, Geetanjali; Xie, Zhihui; Druey, Kirk M

    2009-08-07

    Aberrant activity of the phosphatidylinositol 3-kinase (PI3K) pathway supports growth of many tumors including those of breast, lung, and prostate. Resistance of breast cancer cells to targeted chemotherapies including tyrosine kinase inhibitors (TKI) has been linked to persistent PI3K activity, which may in part be due to increased membrane expression of epidermal growth factor (EGF) receptors (HER2 and HER3). Recently we found that proteins of the RGS (regulator of G protein signaling) family suppress PI3K activity downstream of the receptor by sequestering its p85alpha subunit from signaling complexes. Because a substantial percentage of breast tumors have RGS16 mutations and reduced RGS16 protein expression, we investigated the link between regulation of PI3K activity by RGS16 and breast cancer cell growth. RGS16 overexpression in MCF7 breast cancer cells inhibited EGF-induced proliferation and Akt phosphorylation, whereas shRNA-mediated extinction of RGS16 augmented cell growth and resistance to TKI treatment. Exposure to TKI also reduced RGS16 expression in MCF7 and BT474 cell lines. RGS16 bound the amino-terminal SH2 and inter-SH2 domains of p85alpha and inhibited its interaction with the EGF receptor-associated adapter protein Gab1. These results suggest that the loss of RGS16 in some breast tumors enhances PI3K signaling elicited by growth factors and thereby promotes proliferation and TKI evasion downstream of HER activation.

  10. Oridonin inhibits breast cancer growth and metastasis through blocking the Notch signaling

    Directory of Open Access Journals (Sweden)

    Shixin Xia

    2017-05-01

    Full Text Available Background: Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to inhibit growth and metastasis of human breast cancer cells. Methods: The effect of oridonin on proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in human breast cancer cells. The inhibitive effect of oridonin in vivo was determined by using xenografted nude mice. In addition, the expression of Notch receptors (Notch 1–4 was detected by western blot. Results: Oridonin inhibited human breast cancer cells in vitro and in vivo. In addition, oridonin significantly induced human breast cancer cells apoptosis. Furthermore, the oridonin treatment not only inhibited cancer cell migration and invasion, but more significantly, decreased the expression of Notch 1-4 protein. Conclusion: Our results suggest that the inhibitive effect of oridonin is likely to be driven by the inhibition of Notch signaling pathway and the resulting increased apoptosis.

  11. Breast cancer imaging

    International Nuclear Information System (INIS)

    Funke, M.; Villena, C.

    2008-01-01

    Advances in female breast imaging have substantially influenced the diagnosis, therapy, and prognosis of breast cancer in the past few years. Mammography using conventional or digital technique is considered the gold standard for the early detection of breast cancer. Other modalities such as breast ultrasound and contrast-enhanced magnetic resonance imaging of the breast play an important role in diagnostic imaging, staging, and follow-up of breast cancer. Percutaneous needle biopsy is a faster, less invasive, and more cost-effective method than surgical biopsy for verifying the histological diagnosis. New methods such as breast tomosynthesis, contrast-enhanced mammography, and positron emission tomography promise to further improve breast imaging. Further studies are mandatory to adapt these new methods to clinical needs and to evaluate their performance in clinical practice. (orig.) [de

  12. Characterization of genomic alterations in radiation-associated breast cancer among childhood cancer survivors, using comparative genomic hybridization (CGH arrays.

    Directory of Open Access Journals (Sweden)

    Xiaohong R Yang

    Full Text Available Ionizing radiation is an established risk factor for breast cancer. Epidemiologic studies of radiation-exposed cohorts have been primarily descriptive; molecular events responsible for the development of radiation-associated breast cancer have not been elucidated. In this study, we used array comparative genomic hybridization (array-CGH to characterize genome-wide copy number changes in breast tumors collected in the Childhood Cancer Survivor Study (CCSS. Array-CGH data were obtained from 32 cases who developed a second primary breast cancer following chest irradiation at early ages for the treatment of their first cancers, mostly Hodgkin lymphoma. The majority of these cases developed breast cancer before age 45 (91%, n = 29, had invasive ductal tumors (81%, n = 26, estrogen receptor (ER-positive staining (68%, n = 19 out of 28, and high proliferation as indicated by high Ki-67 staining (77%, n = 17 out of 22. Genomic regions with low-copy number gains and losses and high-level amplifications were similar to what has been reported in sporadic breast tumors, however, the frequency of amplifications of the 17q12 region containing human epidermal growth factor receptor 2 (HER2 was much higher among CCSS cases (38%, n = 12. Our findings suggest that second primary breast cancers in CCSS were enriched for an "amplifier" genomic subgroup with highly proliferative breast tumors. Future investigation in a larger irradiated cohort will be needed to confirm our findings.

  13. Functional inhibition of Ubiquitin conjugating Enzyme (UBE2C) reduces proliferation and sensitizes cervical and breast cancer cells to radiation, doxorubicin, tamoxifen and letrozole

    International Nuclear Information System (INIS)

    Bose, Mayil Vahanan; Rawat, Akhilesh; Gopisetty, Gopal; Thangarajan, Rajkumar; Ganesharaja, Selvaluxmy

    2014-01-01

    Cervical cancer is the second most common cancer in women, worldwide. About 80% of cervical cancer cases occur in developing countries. Breast cancer has overtaken cervical cancer in most of the urban centers in India. In recent years, interest in the role of Ubiquitin conjugating Enzyme E2C (UBE2C) in cancer has shown a dramatic increase. Several studies have reported UBE2C as a potential oncogene and therapeutic target. The objective of the study was to elucidate radiation and chemo-sensitivity in response to functional inhibition of UBE2C in cervical and breast cancer cell lines. Taqman Real time PCR was performed to measure UBE2C levels in cervical and breast cancer cell lines. A dominant negative form of UBE2C (DN-UBE2C) was used to functionally inhibit wild type UBE2C. Cell proliferation and anchorage independent growth were measured by colorimetric assay and soft agar assay respectively. Radiation and chemo response of cell lines were assessed by colorimetric assay and clonogenic assay. Difference in sensitivity to radiation was observed among the cervical cancer cell lines studied. The growth rate of SiHa and HeLa transfected with DN- UBE2C was significantly reduced compared to vector control. Further, DN-UBE2C mediated radio-sensitivity was correlated with a significant decrease in resistance to radiation by SiHa and HeLa cells after transfection when compared to control cultures. Similarly, both the growth rate and the anchorage independent growth of MCF7 and MDAMB231 cells transfected with DN-UBE2C were significantly reduced compared to cells transfected with vector alone. MCF7 and MDAMB231 cells expressing DN-UBE2C were significantly more sensitive to different doses of radiation and doxorubicin compared to controls. In addition, DN-UBE2C transfected MCF7 cells were more sensitive to inhibition by tamoxifen and letrozole compared to vector controls. These results suggest that UBE2C can be used as a potential therapeutic target for cervical and breast

  14. Breast Cancer Disparities

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  15. Breast cancer

    African Journals Online (AJOL)

    A collaborative article gives an overview of breast cancer in LICs, ... approach to the problem; therefore they are published as two separate ... attached to the diagnosis of breast cancer. ... Their founding statement in its early form is included.

  16. Breast cancer and amyloid bodies: is there a role for amyloidosis in cancer-cell dormancy?

    Directory of Open Access Journals (Sweden)

    Mizejewski GJ

    2017-04-01

    Full Text Available Gerald J Mizejewski Wadsworth Center, New York State Department of Health, Albany, NY, USA Abstract: Breast cancer and Alzheimer’s disease (AD are major causes of death in older women. Interestingly, breast cancer occurs less frequently in AD patients than in the general population. Amyloidosis, the aggregation of amyloid proteins to form amyloid bodies, plays a central role in the pathogenesis of AD and other human neuropathies by forming intracellular fibrillary proteins. Contrary to popular belief, amyloidosis is a common occurrence in mammalian cells, and has recently been reported to be a natural physiological process in response to environmental stress stimulations (such as pH and temperature extremes, hypoxia, and oxidative stress. Many proteins contain an intrinsic “amyloid-converting motif”, which acts in conjunction with a specific noncoding RNA to induce formation of proteinaceous amyloid bodies that are stored in intracellular bundles. In cancer cells such as breast and prostate, the process of amyloidosis induces cells to enter a dormant or resting stage devoid of cell division and proliferation. Therefore, cancer cells undergo growth cessation and enter a dormant stage following amyloidosis in the cell; this is akin to giving the cell AD to cease growth. Keywords: α-fetoprotein, noncoding RNA, amyloid bodies, dormancy, breast cancer, Alzheimer’s disease

  17. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Ciriello, Giovanni; Gatza, Michael L; Beck, Andrew H; Wilkerson, Matthew D; Rhie, Suhn K; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C; Tse, Gary M K; Factor, Rachel E; Collins, Laura C; Allison, Kimberly H; Chen, Yunn-Yi; Jensen, Kristin; Johnson, Nicole B; Oesterreich, Steffi; Mills, Gordon B; Cherniack, Andrew D; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W; Hoadley, Katherine A; King, Tari A; Perou, Charles M

    2015-10-08

    Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Chemokine CXCL16 Expression Suppresses Migration and Invasiveness and Induces Apoptosis in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yeying Fang

    2014-01-01

    Full Text Available Background. Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cells in vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells. Methods. Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels. In vitro and in vivo studies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells. Results. We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with the in vitro data, CXCL16 overexpression inhibited tumorigenesis in vivo. Conclusions. Cellular CXCL16 suppresses invasion and metastasis of breast cancer cells in vitro and inhibits tumorigenesis in vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.

  19. miR-216b suppresses breast cancer growth and metastasis by targeting SDCBP

    International Nuclear Information System (INIS)

    Jana, Samir; Sengupta, Suman; Biswas, Subir; Chatterjee, Annesha; Roy, Himansu; Bhattacharyya, Arindam

    2017-01-01

    Breast cancer is the most deadly cancer among women and the second leading cause of cancer death worldwide. Treatment effectiveness is complicated with tumor invasiveness/drug resistance. To tailor treatments more effectively to individual patients, it is important to define tumor growth and metastasis at molecular levels. SDCBP is highly overexpressed and associated with a strikingly poor prognosis in breast cancer. However the post transcriptional regulation of SDCBP overexpression remains to be an unexplored area. Our study reveals that miR-216b directly regulates SDCBP expression by binding to its 3′UTR region. miR-216b is a tumor suppressive miRNA and it is underexpressed during metastatic breast cancer. Consequently, overexpression of miR-216b resulted in decreased proliferation, migration and invasion in BC cell lines by modulating the expression of SDCBP. Inhibition of miR-216b divergent the tumor suppressive role by inducing the growth proliferation, migration and invasion in vitro. There is therefore a negative correlation between the expression of miR-216b and its target gene SDCBP in the BC tissue samples as well as cell lines. Simultaneous expression of miR-216b and SDCBP rescued the growth, migration and invasion effect suggesting that tumor suppressive action of miR-216b may be directly mediated by SDCBP. In summary, the study identifies miR-216b as a regulator of SDCBP expression in breast cancer which can potentially be targeted for developing newer therapies for the effective treatment of this killer disease.

  20. Gene expression signature in organized and growth arrested mammaryacini predicts good outcome in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Martin, Katherine J.; Kenny, Paraic A.; Xhaja, Kris; Bosch, Irene; Yaswen, Paul; Bissell, Mina J.

    2006-02-08

    To understand how non-malignant human mammary epithelial cells (HMEC) transit from a disorganized proliferating to an organized growth arrested state, and to relate this process to the changes that occur in breast cancer, we studied gene expression changes in non-malignant HMEC grown in three-dimensional cultures, and in a previously published panel of microarray data for 295 breast cancer samples. We hypothesized that the gene expression pattern of organized and growth arrested mammary acini would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in two HMEC cell lines, 184 (finite life span) and HMT3522 S1 (immortal non-malignant), on successive days post-seeding in a laminin-rich extracellular matrix assay. Both HMECs underwent growth arrest in G0/G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines. We show that genes that are significantly lower in the organized, growth arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically.

  1. The contribution of cholesterol and epigenetic changes to the pathophysiology of breast cancer.

    Science.gov (United States)

    Munir, Maliha T; Ponce, Christopher; Powell, Catherine A; Tarafdar, Kaiser; Yanagita, Teru; Choudhury, Mahua; Gollahon, Lauren S; Rahman, Shaikh M

    2018-05-04

    Breast cancer is one of the most commonly diagnosed cancers in women. Accumulating evidence suggests that cholesterol plays an important role in the development of breast cancer. Even though the mechanistic link between these two factors is not well understood, one possibility is that dysregulated cholesterol metabolism may affect lipid raft and membrane fluidity and can promote tumor development. Current studies have shown oxysterol 27-hydroxycholesterol (27-HC) as a critical regulator of cholesterol and breast cancer pathogenesis. This is supported by the significantly higher expression of CYP27A1 (cytochrome P450, family 27, subfamily A, polypeptide 1) in breast cancers. This enzyme is responsible for 27-HC synthesis from cholesterol. It has been shown that 27-HC can not only increase the proliferation of estrogen receptor (ER)-positive breast cancer cells but also stimulate tumor growth and metastasis in several breast cancer models. This phenomenon is surprising since 27-HC and other oxysterols generally reduce intracellular cholesterol levels by activating the liver X receptors (LXRs). Resolving this paradox will elucidate molecular pathways by which cholesterol, ER, and LXR are connected to breast cancer. These findings will also provide the rationale for evaluating pharmaceutical approaches that manipulate cholesterol or 27-HC synthesis in order to mitigate the impact of cholesterol on breast cancer pathophysiology. In addition to cholesterol, epigenetic changes including non-coding RNAs, and microRNAs, DNA methylation, and histone modifications, have all been shown to control tumorigenesis. The purpose of this review is to discuss the link between altered cholesterol metabolism and epigenetic modification during breast cancer progression. Copyright © 2018. Published by Elsevier Ltd.

  2. Suppression of WIF-1 through promoter hypermethylation causes accelerated proliferation of the aryl hydrocarbon receptor (AHR) overexpressing MCF10AT1 breast cancer cells

    International Nuclear Information System (INIS)

    Wu, Dalei; Wong, Patrick; Li, Wen; Vogel, Christoph F.; Matsumura, Fumio

    2011-01-01

    Highlights: → 5-Aza-2'-deoxycytidine (AZ) causes proliferation suppression and ERα recovery. → AZ down-regulates Wnt/β-catenin pathway mainly by increasing WIF-1 expression. → Both ERα and AhR have some effects on DNA methylation in breast cancer cells. → Artificial overexpression of ERα in ER negative cells increases WIF-1 expression. → WIF-1 promoter hypermethylation is one of the major causes for accelerated proliferation. -- Abstract: The cause for increased cell proliferation in AHR overexpressing breast cancer cells still remains unknown. Here we studied the molecular basis of aggressive cell proliferation of an AHR overexpressing and ERα functionally down-regulated MCF10AT1 cell line, designated as P20E, in comparison to a matched sub-line, P20C with normal AHR expression and ERα function. We found that a 4-day treatment of P20E cells with 5-aza-2'-deoxycytidine (AZ) caused a significant suppression of cell proliferation. Such an effect of AZ was accompanied with the significant recovery of ERα function. Among diagnostic markers of AZ-induced cellular changes we found conspicuous up-regulation of mRNA expression of Wnt inhibitory factor-1 (WIF-1), particularly in P20E. The possibility of AZ-induced demethylation on the promoter of WIF-1 gene was confirmed through methylation specific PCR assay. Such AZ-induced changes in P20E cells were also accompanied with the decrease in the binding of nuclear proteins to the 32 P labeled TRE (TCF response element) and the reduced accumulation of β-catenin protein in the cell nucleus, indicating the importance of Wnt/β-catenin pathway in maintaining the increased cell proliferation in P20E line over P20C line. The importance of WIF-1 in this regard has been validated by transfecting cells with siRNA against WIF-1, which caused an increase in cell proliferation. Moreover, artificial overexpression of ERα in both P20E as well as MDA-MB-231 cells increased the mRNA expression of WIF-1. Together these

  3. Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

    Science.gov (United States)

    2013-01-01

    Background Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. Methods Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. Results In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using

  4. Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures

    International Nuclear Information System (INIS)

    Eigėlienė, Natalija; Härkönen, Pirkko; Erkkola, Risto

    2006-01-01

    Human breast tissue undergoes phases of proliferation, differentiation and regression regulated by changes of the levels of circulating sex hormones during the menstrual cycle or aging. Ovarian hormones also likely play a key role in the etiology and biology of breast cancer. Reports concerning the proliferative effects of steroid hormones on the normal epithelium of human breast have been conflicting. Some studies have shown that steroid hormones may predispose breast epithelial cells to malignant changes by stimulating their proliferation, which is known to be regulated tightly by stromal cells. The aim of this study was to investigate the effects of 17β-estradiol and medroxyprogesterone acetate on proliferation, apoptosis, expression of differentiation markers and steroid hormone receptors in breast epithelium using an in vitro model of freshly isolated human breast tissue, in which a proper interaction of breast epithelium and stroma has been maintained. Human breast tissues were obtained from women undergoing surgery for breast tumours. Peritumoral tissues were excised and explants were cultured for 3 weeks in medium supplemented with E 2 or MPA or with E 2 +MPA. Endpoints included histopathological, histomorphometric and immunohistochemical assessment of the breast explants. Culture of breast explants for 14 or 21 days with steroid hormones increased proliferative activity and the thickness of acinar and ductal epithelium. E 2 -treatment led to hyperplastic epithelial morphology, MPA to hypersecretory single-layered epithelium and E 2 +MPA to multilayered but organised epithelium. The proliferative response to E 2 in comparison to control (p < 0.001) was more pronounced than to MPA (p < 0.05) or E 2 +MPA (p < 0.05) at 7 and 14 days for Ki-67 and PCNA. E 2 treatment also decreased the proportion of apoptotic cells after 7 (p < 0.01) and 14 (p < 0.01) days. In addition, the relative number of ERα, ERβ and PR positive epithelial cells was decreased by all

  5. DIAGNOSIS OF MUCINOUS BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. К. Saribekyan

    2014-01-01

    Full Text Available The paper presents the diagnostic results of 27 patients with mucinous breast cancer, which is a rare type of invasive ductal breast cancer accounting for less than 2% of all breast cancers. The role of radiological, histological and cytological examination in the diagnosis of mucinous breast cancer is evaluated. In cases with large tumors, it was difficult to differentiate mucinous breast cancer from fibrocystic and other benign breast lesions.

  6. Evaluation of the Cytotoxic and Autophagic Effects of Atorvastatin on MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Tuğba Alarcon Martinez

    2018-05-01

    Full Text Available Background: Recently, cytotoxic effects of statins on breast cancer cells have been reported. However, the mechanism of anti-proliferative effects is currently unknown. Autophagy is non-apoptotic programmed cell death, which is characterized by degradation of cytoplasmic components and as having a role in cancer pathogenesis. Aims: To investigate the anti-proliferative effects of atorvastatin on MCF-7 human breast adenocarcinoma cells with respect to both autophagy and apoptosis. Study Design: Cell culture study. Methods: Cell viability was analyzed using WST-1 cell proliferation assay. Apoptosis was determined by the TUNEL method, whereas autophagy was assessed by Beclin-1 and LC3B immunofluorescence staining. Ultrastructural analysis of cells was performed by electron microscopy. Results: Atorvastatin reduced MCF-7 cell proliferation in a dose- and time-dependent manner inducing TUNEL-, Beclin-1-, and LC3B-positive cells. Moreover, ultrastructural analysis showed apoptotic, autophagic, and necrotic morphological changes in treatment groups. A statistically significant increase in the apoptotic index was detected with higher concentrations of atorvastatin at 24 h and 48 h (p<0.05. Conclusion: The anti-proliferative effects of atorvastatin on breast cancer cells is mediated by the induction of both apoptosis and autophagy which shows statins as a potential treatment option for breast cancer.

  7. Is α/β for breast cancer really low?

    International Nuclear Information System (INIS)

    Qi, X. Sharon; White, Julia; Li, X. Allen

    2011-01-01

    Purpose: Low α/β ratio for breast cancer has drawn a growing interest for exploring hypofractionation for breast irradiation. This work is to confirm the low α/β ratio based on large randomized clinical trials of breast irradiation. Methods and materials: A model based on the generalized linear-quadratic (LQ) model and Poisson statistical model was developed to calculate disease-free survival with consideration of clonogen proliferation during the course of radiation treatment and exponential behavior of survival rate with follow-up time. Outcome data from a series of randomized clinical trials of early-stage breast radiotherapy were fitted to estimate the model parameters. Other clinical outcomes, including treatments with surgery alone or radiotherapy alone were used to validate the model and the estimated parameters. Hypofractionation regimens were proposed based on the newly estimated LQ parameters. Results: Plausible population averaged radiobiologic parameters for breast cancer (95% confidence level) are α/β = 2.88 (0.75-5.01) Gy; α = 0.08 ± 0.02 Gy -1 ; potential doubling time T d = 14.4 ± 7.8 day. The analysis of the radiation-alone data suggested an α/β ratio of 3.89 ± 6.25 Gy, verifying the low α/β ratio based on the post-lumpectomy irradiation data. The hypofractionation regimens that are equivalent to the conventional regimen of 2.0 Gy x 25 in 5 weeks include 2.26 Gy x 20, 3.34 Gy x 10, 4.93 Gy x 5 or 3.39 Gy x 10 (BID). Conclusions: The analysis of the available clinical data from multiple institutions support that breast cancer has a low ratio of α/β, encouraging hypofractionated radiotherapy regimens for breast cancer.

  8. Exploring the breast cancer patient journey: do breast cancer survivors need menopause management support?

    Science.gov (United States)

    Tanna, Nuttan; Buijs, Helene; Pitkin, Joan

    2011-12-01

    Breast cancer survivors can be expected to suffer from menopause symptoms with estrogen deprivation due to cancer treatments, in addition to natural menopause-related estrogen loss. To gain an understanding of what support breast cancer patients have when they suffer from menopausal symptoms, and utilize findings to further inform National Health Service (NHS) care provision for breast cancer survivors. Qualitative study with focus group sessions targeting Caucasian and Asian women with breast cancer. Patient stories, with women describing their breast cancer journey and speaking about support received for any menopausal symptoms. Thematic data analysis of transcription. Breast cancer patients were not sure if they had menopausal symptoms or whether this was due to their breast cancer condition or treatment. Patients had an attitude of acceptance of menopausal symptoms and reported trying to cope with these by themselves. This research identifies a need for more information that is culturally sensitive on managing menopause symptoms, both as side-effects of breast cancer treatments as well as for affect on quality of life during the survivorship phase. Our work also gives insight into cultural remedies used for hot flushes by Asian patients, which they consider as 'cooling' foods. Breast cancer patients want to know whether side-effects of cancer treatment persist long term and how these can be managed. There is a need for improved patient support within any new NHS service models that are developed along breast cancer patient pathways, and inclusion of personalized advice for menopause symptoms.

  9. The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer

    Science.gov (United States)

    2018-03-02

    Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

  10. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

    Science.gov (United States)

    Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

    2010-05-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

  11. Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Lui, Asona; New, Jacob; Ogony, Joshua; Thomas, Sufi; Lewis-Wambi, Joan

    2016-01-01

    mTOR inhibition of aromatase inhibitor (AI)-resistant breast cancer is currently under evaluation in the clinic. Everolimus/RAD001 (Afinitor®) has had limited efficacy as a solo agent but is projected to become part of combination therapy for AI-resistant breast cancer. This study was conducted to investigate the anti-proliferative and resistance mechanisms of everolimus in AI-resistant breast cancer cells. In this study we utilized two AI-resistant breast cancer cell lines, MCF-7:5C and MCF-7:2A, which were clonally derived from estrogen receptor positive (ER+) MCF-7 breast cancer cells following long-term estrogen deprivation. Cell viability assay, colony formation assay, cell cycle analysis and soft agar anchorage-independent growth assay were used to determine the efficacy of everolimus in inhibiting the proliferation and tumor forming potential of MCF-7, MCF-7:5C, MCF-7:2A and MCF10A cells. Confocal microscopy and transmission electron microscopy were used to evaluate LC3-II production and autophagosome formation, while ERE-luciferase reporter, Western blot, and RT-PCR analyses were used to assess ER expression and transcriptional activity. Everolimus inhibited the proliferation of MCF-7:5C and MCF-7:2A cells with relatively equal efficiency to parental MCF-7 breast cancer cells. The inhibitory effect of everolimus was due to G1 arrest as a result of downregulation of cyclin D1 and p21. Everolimus also dramatically reduced estrogen receptor (ER) expression (mRNA and protein) and transcriptional activity in addition to the ER chaperone, heat shock protein 90 protein (HSP90). Everolimus restored 4-hydroxy-tamoxifen (4OHT) sensitivity in MCF-7:5C cells and enhanced 4OHT sensitivity in MCF-7 and MCF-7:2A cells. Notably, we found that autophagy is one method of everolimus insensitivity in MCF-7 breast cancer cell lines. This study provides additional insight into the mechanism(s) of action of everolimus that can be used to enhance the utility of mTOR inhibitors as

  12. Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hao [Department of Chemistry, Jinan University, Guangzhou (China); Zhang, Yikai [Institute of Hematology, Jinan University, Guangzhou (China); Zheng, Shanyuan [School of Life Sciences, The Chinese University of Hong Kong, Hong Kong (China); Weng, Zeping; Ma, Jun [First Affiliated Hospital, Jinan University, Guangzhou (China); Li, Yangqiu [Institute of Hematology, Jinan University, Guangzhou (China); First Affiliated Hospital, Jinan University, Guangzhou (China); Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632 (China); Xie, Xinyuan [Department of Chemistry, Jinan University, Guangzhou (China); Zheng, Wenjie, E-mail: tzhwj@jnu.edu.cn [Department of Chemistry, Jinan University, Guangzhou (China)

    2016-09-02

    Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to “copper” cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cells by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper. - Highlights: • Nano-S selectively inhibited the mitosis of A375 and MCF-7 cells by depleting copper. • Nano-S inactivated MEK/ERK pathway through the detention of copper. • Nano-S improved the cellular uptake and anticancer activities

  13. Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Liu, Hao; Zhang, Yikai; Zheng, Shanyuan; Weng, Zeping; Ma, Jun; Li, Yangqiu; Xie, Xinyuan; Zheng, Wenjie

    2016-01-01

    Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to “copper” cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cells by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper. - Highlights: • Nano-S selectively inhibited the mitosis of A375 and MCF-7 cells by depleting copper. • Nano-S inactivated MEK/ERK pathway through the detention of copper. • Nano-S improved the cellular uptake and anticancer activities

  14. BRD7 inhibits the Warburg effect and tumor progression through inactivation of HIF1α/LDHA axis in breast cancer.

    Science.gov (United States)

    Niu, Weihong; Luo, Yanwei; Wang, Xinye; Zhou, Yao; Li, Hui; Wang, Heran; Fu, Yaojie; Liu, Shanshan; Yin, Shanghelin; Li, Jianglei; Zhao, Ran; Liu, Yukun; Fan, Songqing; Li, Zheng; Xiong, Wei; Li, Xiaoling; Li, Guiyuan; Ren, Caiping; Tan, Ming; Zhou, Ming

    2018-05-03

    The bromodomain-containing protein 7 (BRD7) was first identified as a tumor suppressor in nasopharyngeal carcinoma and has critical roles in cancer development and progression. However, the regulatory roles and mechanisms of BRD7 in cancer metabolism are still unknown. In this study, we demonstrated that BRD7 was lowly expressed in breast cancer tissues and was identified as a poor prognostic factor in breast cancer. Meanwhile, BRD7 could suppress cell proliferation, initiate cell apoptosis and reduce aerobic glycolysis, suggesting that BRD7 plays a tumor suppressive roles in breast cancer. Mechanistically, BRD7 could negatively regulate a critical glycolytic enzyme LDHA through directly interaction with its upstream transcription factor, HIF1α, facilitating degradation of HIF1α mediated by ubiquitin-proteasome pathway. Moreover, restoring the expression of LDHA in breast cancer cells could reverse the effect of BRD7 on aerobic glycolysis, cell proliferation, and tumor formation, as well as the expression of cell cycle and apopotosis related molecules such as cyclin D1, CDK4, P21, and c-PARP both in vitro and in vivo. Taken together, these results indicate that BRD7 acts as a tumor suppressor in breast cancer and represses the glycolysis and tumor progression through inactivation of HIF1α/LDHA transcription axis.

  15. Archives of Breast Cancer: An Academic Multidisciplinary Breast Cancer Forum

    Directory of Open Access Journals (Sweden)

    Ahmad Kaviani

    2014-05-01

    Full Text Available Welcome to Archives of Breast Cancer (ABC, a new journal with sole focus on breast diseases and especially breast cancer. Breast cancer is a devastating disease that impacts many women and threatens their health and wellbeing. A large number of health professionals from a wide spectrum of clinical disciplines, such as surgery, medical oncology, public health, pathology, radiation oncology, diagnostic radiology, and nuclear medicine, are involved in dealing with such a challenging and common disease.The concept of applying a multidisciplinary approach to clinical and non-clinical aspects of breast cancer has been found to be of vital importance to the understanding of this prevalent type of cancer. Such collaboration can also improve the quantity and quality of the research in this field. To this end, journals which choose to publish multidisciplinary articles as their primary focus can serve as the academic forum to share ideas from a variety of expertise. Archives of Breast Cancer can certainly add to the depth and quality of the research in the field. Articles on a single topic would be readily available to the readers from multiple disciplines and all in one journal. This would eventually lead to fruitful interaction among specialists seeking to investigate this disease, yet,from different perspectives. The benefits of this interaction in the process of devising appropriate strategies and approaches in dealing with the problem are crystal clear.The world of medical sciences has witnessed an abundant increase in the quality and quantity of breast-cancer-related research. In the past 20 years, the number of published articles indexed in PubMed from 1994 to 2014 is more than 5 times than the number published before 1993 (about 170,000 compared to 30,000. Meanwhile, the number of PubMed indexed medical journals dedicated to breast cancer research has also risen from 5 in 1993 to 17 in 2014. This increasing trend highlights an essential need for

  16. Breast cancer statistics, 2011.

    Science.gov (United States)

    DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

    2011-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population. Copyright © 2011 American Cancer Society, Inc.

  17. Influence of IFN-gamma and its receptors in human breast cancer

    Directory of Open Access Journals (Sweden)

    Paniagua Ricardo

    2007-08-01

    Full Text Available Abstract Background Interferons are a group of proteins that trigger multiple responses including prevention of viral replication, inhibition of cell growth, and modulation of cell differentiation. In different mammary carcinoma cell lines IFNγ induces growth arrest at mid-G1. At the present there are no in vivo studies in human breast. The aim of this study was to investigate the expression patterns of IFNγ and its two receptors (IFNγ-Rα and IFNγ-Rβ by Western blot and immunohistochemistry, in order to elucidate its role in the different types of human breast cancer (in situ and infiltrative. Methods Immunohistochemical and semiquantitative study of IFNγ, its receptors types (IFNγ-Rα and IFNγ-Rβ, cell proliferation (proliferating cell nuclear antigen, also named PCNA, and apoptosis (TUNEL method was carried between the three breast groups (fibrocystic lesions, in situ tumors and infiltrating tumors. Results In the three groups of patients, IFNγ and IFNγ-Rα immunoreactions appeared in the cytoplasm while IFNγ-Rβ also was found in the nucleus. The optical density to IFNγ was higher in in situ carcinoma than in benign and infiltrating tumors. When we observed IFNγ-Rα, the optical density was lower in infiltrating carcinoma than in benign and in situ tumors (the higher density. To IFNγ-Rβ, the optical density was similar in the three group samples. In tumor samples PCNA and TUNEL index was significantly higher; than in benign diseases. PCNA index increased with the malignance. No significant differences were found between cancer types to TUNEL. IFNγ could be a potential therapeutic tool in breast cancer. However, tumor cells are able to escape from the control of this cytokine in the early tumor stages; this is probably due to a decreased expression of IFNγ, or also to an alteration of either its receptors or some transduction elements. Conclusion We conclude that the decrease in the % positive samples that expressed IFN

  18. miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10

    International Nuclear Information System (INIS)

    Chen, Yating; Zhang, Hongwei; Ma, Duan; Zhang, Jin; Wang, Huijun; Zhao, Jiayi; Xu, Cheng; Du, Yingying; Luo, Xin; Zheng, Fengyun; Liu, Rui

    2012-01-01

    miRNAs are a group of small RNA molecules regulating target genes by inducing mRNA degradation or translational repression. Aberrant expression of miRNAs correlates with various cancers. Although miR-135a has been implicated in several other cancers, its role in breast cancer is unknown. HOXA10 however, is associated with multiple cancer types and was recently shown to induce p53 expression in breast cancer cells and reduce their invasive ability. Because HOXA10 is a confirmed miR-135a target in more than one tissue, we examined miR-135a levels in relation to breast cancer phenotypes to determine if miR-135a plays role in this cancer type. Expression levels of miR-135a in tissues and cells were determined by poly (A)-RT PCR. The effect of miR-135a on proliferation was evaluated by CCK8 assay, cell migration and invasion were evaluated by transwell migration and invasion assays, and target protein expression was determined by western blotting. GFP and luciferase reporter plasmids were constructed to confirm the action of miR-135a on downstream target genes including HOXA10. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student's t-test. Here we report that miR-135a was highly expressed in metastatic breast tumors. We found that the expression of miR-135a was required for the migration and invasion of breast cancer cells, but not their proliferation. HOXA10, which encodes a transcription factor required for embryonic development and is a metastasis suppressor in breast cancer, was shown to be a direct target of miR-135a in breast cancer cells. Our analysis showed that miR-135a suppressed the expression of HOXA10 both at the mRNA and protein level, and its ability to promote cellular migration and invasion was partially reversed by overexpression of HOXA10. In summary, our results indicate that miR-135a is an onco-miRNA that can promote breast cancer cell migration and invasion. HOXA10 is a target gene for mi

  19. Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

    International Nuclear Information System (INIS)

    Jami, Mohammad-Saeid; Huang, Xin; Peng, Hong; Fu, Kai; Li, Yan; Singh, Rakesh K; Ding, Shi-Jian; Hou, Jinxuan; Liu, Miao; Varney, Michelle L; Hassan, Hesham; Dong, Jixin; Geng, Liying; Wang, Jing; Yu, Fang

    2014-01-01

    KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it

  20. Breast Cancer (For Kids)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Breast Cancer KidsHealth / For Kids / Breast Cancer What's in this ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

  1. Who's talking about breast cancer? Analysis of daily breast cancer posts on the internet.

    Science.gov (United States)

    Quinn, Edel M; Corrigan, Mark A; McHugh, Seamus M; Murphy, David; O'Mullane, John; Hill, Arnold D; Redmond, Henry Paul

    2013-02-01

    Breast cancer is the cancer most commonly searched for on the internet. Our aim was to assess daily new breast cancer related posting on the internet. We analyzed numbers of new daily posts for common cancers for one month and subsequently analyzed content of 1426 breast cancer related posts. We also assessed use of online discussion forums for breast cancer related dialogue. Breast related topics had significantly more posts per day compared to others (mean 66.7, p Anonymous posts were common (55%) and less likely to be accurate (p internet has become a primary forum within which health information, particularly relating to breast cancer, is both sought and shared. Increasingly information is provided by patients themselves. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Dichotomous roles for the orphan nuclear receptor NURR1 in breast cancer

    International Nuclear Information System (INIS)

    Llopis, Shawn; Singleton, Brittany; Duplessis, Tamika; Carrier, Latonya; Rowan, Brian; Williams, Christopher

    2013-01-01

    NR4A orphan nuclear receptors are involved in multiple biological processes which are important in tumorigenesis such as cell proliferation, apoptosis, differentiation, and glucose utilization. The significance of NR4A family member NURR1 (NR4A2) in breast cancer etiology has not been elucidated. The purpose of this study was to ascertain the impact of NURR1 expression on breast transformation, tumor growth, and breast cancer patient survival. We determined the expression of NURR1 in normal breast versus breast carcinoma in tissue microarrays (immunohistochemistry), tissue lysates (immunoblot), and at the mRNA level (publically available breast microarrays). In addition NURR1 expression was compared among breast cancer patients in cohorts based on p53 expression, estrogen receptor α expression, tumor grade, and lymph node metastases. Kaplan-Meier survival plots were used to determine the correlation between NURR1 expression and relapse free survival (RFS). Using shRNA-mediated silencing, we determined the effect of NURR1 expression on tumor growth in mouse xenografts. Results from breast cancer tissue arrays demonstrate a higher NURR1 expression in the normal breast epithelium compared to breast carcinoma cells (p ≤ 0.05). Among cases of breast cancer, NURR1 expression in the primary tumors was inversely correlated with lymph node metastases (p ≤ 0.05) and p53 expression (p ≤ 0.05). Clinical stage and histological grade were not associated with variation in NURR1 expression. In gene microarrays, 4 of 5 datasets showed stronger mean expression of NURR1 in normal breast as compared to transformed breast. Additionally, NURR1 expression was strongly correlated with increase relapse free survival (HR = 0.7) in a cohort of all breast cancer patients, but showed no significant difference in survival when compared among patients whom have not been treated systemically (HR = 0.91). Paradoxically, NURR1 silenced breast xenografts showed significantly decreased growth

  3. BAG3 promotes tumour cell proliferation by regulating EGFR signal transduction pathways in triple negative breast cancer.

    Science.gov (United States)

    Shields, Sarah; Conroy, Emer; O'Grady, Tony; McGoldrick, Alo; Connor, Kate; Ward, Mark P; Useckaite, Zivile; Dempsey, Eugene; Reilly, Rebecca; Fan, Yue; Chubb, Anthony; Matallanas, David Gomez; Kay, Elaine W; O'Connor, Darran; McCann, Amanda; Gallagher, William M; Coppinger, Judith A

    2018-03-20

    Triple-negative breast cancer (TNBC), is a heterogeneous disease characterised by absence of expression of the estrogen receptor (ER), progesterone receptor (PR) and lack of amplification of human epidermal growth factor receptor 2 (HER2). TNBC patients can exhibit poor prognosis and high recurrence stages despite early response to chemotherapy treatment. In this study, we identified a pro-survival signalling protein BCL2- associated athanogene 3 (BAG3) to be highly expressed in a subset of TNBC cell lines and tumour tissues. High mRNA expression of BAG3 in TNBC patient cohorts significantly associated with a lower recurrence free survival. The epidermal growth factor receptor (EGFR) is amplified in TNBC and EGFR signalling dynamics impinge on cancer cell survival and disease recurrence. We found a correlation between BAG3 and EGFR expression in TNBC cell lines and determined that BAG3 can regulate tumour cell proliferation, migration and invasion in EGFR expressing TNBC cells lines. We identified an interaction between BAG3 and components of the EGFR signalling networks using mass spectrometry. Furthermore, BAG3 contributed to regulation of proliferation in TNBC cell lines by reducing the activation of components of the PI3K/AKT and FAK/Src signalling subnetworks. Finally, we found that combined targeting of BAG3 and EGFR was more effective than inhibition of EGFR with Cetuximab alone in TNBC cell lines. This study demonstrates a role for BAG3 in regulation of distinct EGFR modules and highlights the potential of BAG3 as a therapeutic target in TNBC.

  4. Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary

    Directory of Open Access Journals (Sweden)

    Wood Charles E

    2008-06-01

    Full Text Available Abstract There has been considerable investigation of the potential for soyfoods to reduce risk of cancer, and in particular cancer of the breast. Most interest in this relationship is because soyfoods are essentially a unique dietary source of isoflavones, compounds which bind to estrogen receptors and exhibit weak estrogen-like effects under certain experimental conditions. In recent years the relationship between soyfoods and breast cancer has become controversial because of concerns – based mostly on in vitro and rodent data – that isoflavones may stimulate the growth of existing estrogen-sensitive breast tumors. This controversy carries considerable public health significance because of the increasing popularity of soyfoods and the commercial availability of isoflavone supplements. In this analysis and commentary we attempt to outline current concerns regarding the estrogen-like effects of isoflavones in the breast focusing primarily on the clinical trial data and place these concerns in the context of recent evidence regarding estrogen therapy use in postmenopausal women. Overall, there is little clinical evidence to suggest that isoflavones will increase breast cancer risk in healthy women or worsen the prognosis of breast cancer patients. Although relatively limited research has been conducted, and the clinical trials often involved small numbers of subjects, there is no evidence that isoflavone intake increases breast tissue density in pre- or postmenopausal women or increases breast cell proliferation in postmenopausal women with or without a history of breast cancer. The epidemiologic data are generally consistent with the clinical data, showing no indication of increased risk. Furthermore, these clinical and epidemiologic data are consistent with what appears to be a low overall breast cancer risk associated with pharmacologic unopposed estrogen exposure in postmenopausal women. While more research is required to definitively

  5. Breast Cancer Risk in American Women

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Risk in American Women On This Page What ... risk of developing the disease. Personal history of breast cancer : Women who have had breast cancer are more ...

  6. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    International Nuclear Information System (INIS)

    Cárdenas, Casimiro; Quesada, Ana R.; Medina, Miguel Ángel

    2014-01-01

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells

  7. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas, Casimiro [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); Research Support Central Services (SCAI) of the University of Málaga, E-29071 Málaga (Spain); Quesada, Ana R. [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain); Medina, Miguel Ángel, E-mail: medina@uma.es [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain)

    2014-05-09

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.

  8. PBX1 Genomic Pioneer Function Drives ERα Signaling Underlying Progression in Breast Cancer

    Science.gov (United States)

    Magnani, Luca; Ballantyne, Elizabeth B.; Zhang, Xiaoyang; Lupien, Mathieu

    2011-01-01

    Altered transcriptional programs are a hallmark of diseases, yet how these are established is still ill-defined. PBX1 is a TALE homeodomain protein involved in the development of different types of cancers. The estrogen receptor alpha (ERα) is central to the development of two-thirds of all breast cancers. Here we demonstrate that PBX1 acts as a pioneer factor and is essential for the ERα-mediated transcriptional response driving aggressive tumors in breast cancer. Indeed, PBX1 expression correlates with ERα in primary breast tumors, and breast cancer cells depleted of PBX1 no longer proliferate following estrogen stimulation. Profiling PBX1 recruitment and chromatin accessibility across the genome of breast cancer cells through ChIP-seq and FAIRE-seq reveals that PBX1 is loaded and promotes chromatin openness at specific genomic locations through its capacity to read specific epigenetic signatures. Accordingly, PBX1 guides ERα recruitment to a specific subset of sites. Expression profiling studies demonstrate that PBX1 controls over 70% of the estrogen response. More importantly, the PBX1-dependent transcriptional program is associated with poor-outcome in breast cancer patients. Correspondingly, PBX1 expression alone can discriminate a priori the outcome in ERα-positive breast cancer patients. These features are markedly different from the previously characterized ERα-associated pioneer factor FoxA1. Indeed, PBX1 is the only pioneer factor identified to date that discriminates outcome such as metastasis in ERα-positive breast cancer patients. Together our results reveal that PBX1 is a novel pioneer factor defining aggressive ERα-positive breast tumors, as it guides ERα genomic activity to unique genomic regions promoting a transcriptional program favorable to breast cancer progression. PMID:22125492

  9. Mammographic Breast Density in Malaysian Women with Breast Cancer

    International Nuclear Information System (INIS)

    Noriah Jamal; Humairah Samad Cheung

    2016-01-01

    The objective of this study was to examine the mammographic breast density of women with breast cancer detected on voluntary mammographic screening at two selected screening centers in Malaysia. This was a retrospective study of Full-Field Digital Mammography (FFDM) images of 150 Malaysian women with biopsy-proven breast cancer. The study population comprised 73 Malays (37.7 %), 59 Chinese (39.3 %) and 18 Indians (12.0 %). The Tabar breast density Patterns (I - V) were used to evaluate mammographic breast density. Data were analyzed using descriptive statistics. The results were compared with findings from a similar study on a group of 668 women who did not have breast cancer. The results showed that 44.7 % of the study population had dense breasts (Patterns IV and V), 14.7 % had predominantly fatty breasts (Patterns II and III) while 40.7 % had Pattern I. The proportion of study population with dense breasts decreased with age. In conclusion, the proportion of women with dense breasts decreased with age. Majority of the women with cancer (44.7 %) had dense breasts of Tabar Patterns IV and V, which has been associated with increased risk of breast cancer detected by voluntary mammographic screening. The results support the notion that increased breast density is a risk factor of breast cancer. (author)

  10. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  11. Breast cancer in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, S.; Ramsey-Goldman, R.; Petri, M.

    2017-01-01

    Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi......-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results...... There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug...

  12. Expression of hypoxia-inducible factor-1α and cell cycle proteins in invasive breast cancer are estrogen receptor related

    International Nuclear Information System (INIS)

    Bos, Reinhard; Diest, Paul J van; Groep, Petra van der; Shvarts, Avi; Greijer, Astrid E; Wall, Elsken van der

    2004-01-01

    The transcription factor hypoxia-inducible factor-1 (HIF-1) is a key regulator of the cellular response to hypoxia. Previous studies showed that concentrations of its subunit HIF-1α, as a surrogate for HIF-1 activity, are increased during breast carcinogenesis and can independently predict prognosis in breast cancer. During carcinogenesis, the cell cycle is progressively deregulated, and proliferation rate is a strong prognostic factor in breast cancer. In this study we undertook a detailed evaluation of the relationships between HIF-1α and cell cycle-associated proteins. In a representative estrogen receptor (ER) group of 150 breast cancers, the expression of HIF-1α, vascular endothelial growth factor, the ER, HER-2/neu, Ki-67, cyclin A, cyclin D 1 , p21, p53, and Bcl-2 was investigated by immunohistochemistry. High concentrations (5% or more) of HIF-1α were associated with increased proliferation as shown by positive correlations with Ki-67 (P < 0.001) and the late S–G2-phase protein cyclin A (P < 0.001), but not with the G1-phase protein cyclin D 1 . High HIF-1α concentrations were also strongly associated with p53 positivity (P < 0.001) and loss of Bcl-2 expression (P = 0.013). No association was found between p21 and HIF-1α (P = 0.105) in the whole group of patients. However, the subgroup of ER-positive cancers was characterized by a strong positive association between HIF-1α and p21 (P = 0.023), and HIF-1α lacked any relation with proliferation. HIF-1α overexpression is associated with increased proliferation, which might explain the adverse prognostic impact of increased concentrations of HIF-1α in invasive breast cancer. In ER-positive tumors, HIF-1α is associated with p21 but not against proliferation. This shows the importance of further functional analysis to unravel the role of HIF-1 in late cell cycle progression, and the link between HIF-1, p21, and ER

  13. Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening.

    Science.gov (United States)

    Autier, Philippe; Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

    2016-01-01

    The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates. The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk. The observed and predicted RR of breast cancer death were 0.72 (0.56-0.94) and 0.98 (0.77-1.24) in the HIP trial, and 0.79 (0.78-1.01) and 0.90 (0.80-1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62-0.87), while the predicted RR was 0.89 (0.75-1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70-0.97) if extra cancers were excluded. In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.

  14. Estrogen signalling and the DNA damage response in hormone dependent breast cancers

    Directory of Open Access Journals (Sweden)

    C Elizabeth Caldon

    2014-05-01

    Full Text Available Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1 and p53 and the feedback on estrogen receptor signalling from these proteins. We put forward the hypothesis that estrogen receptor signalling converges to suppress effective DNA repair and apoptosis in favour of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer which will further change the processing of DNA damage. Finally the action of estrogen signalling on DNA damage is also relevant to the therapeutic setting as the suppression of a DNA damage response by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.

  15. Internalization: acute apoptosis of breast cancer cells using herceptin-immobilized gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Rathinaraj P

    2015-02-01

    Full Text Available Pierson Rathinaraj,1 Ahmed M Al-Jumaily,1 Do Sung Huh21Institute of Biomedical Technologies, Auckland University of Technology, Auckland, New Zealand; 2Department of Nano science and Engineering, Inje University, Gimhea, South KoreaAbstract: Herceptin, the monoclonal antibody, was successfully immobilized on gold nanoparticles (GNPs to improve their precise interactions with breast cancer cells (SK-BR3. The mean size of the GNPs (29 nm, as determined by dynamic light scattering, enlarged to 82 nm after herceptin immobilization. The in vitro cell culture experiment indicated that human skin cells (FB proliferated well in the presence of herceptin-conjugated GNP (GNP–Her, while most of the breast cancer cells (SK-BR3 had died. To elucidate the mechanism of cell death, the interaction of breast cancer cells with GNP–Her was tracked by confocal laser scanning microscopy. Consequently, GNP–Her was found to be bound precisely to the membrane of the breast cancer cell, which became almost saturated after 6 hours incubation. This shows that the progression signal of SK-BR3 cells is retarded completely by the precise binding of antibody to the human epidermal growth factor receptor 2 receptor of the breast cancer cell membrane, causing cell death.Keywords: herceptin, gold nanoparticles, SK-BR3 cells, intracellular uptake

  16. Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells

    International Nuclear Information System (INIS)

    Rashid-Kolvear, Fariborz; Taboski, Michael AS; Nguyen, Johnny; Wang, Dong-Yu; Harrington, Lea A; Done, Susan J

    2010-01-01

    Breast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated. In this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference. We demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's t test. To our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined

  17. Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jin [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Qiang [Department of Hematology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jiandong [Department of Hepatobiliary Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Ren, Qinyou [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Cao, Wei [Department of Interventional Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jingyue; Yu, Zhaocai [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yu, Fang [Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, Xi' an, Shaanxi (China); Wu, Yanlan [Department of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Shi, Hengjun [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Wenchao [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China)

    2012-04-27

    A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

  18. Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

    International Nuclear Information System (INIS)

    Zheng, Jin; Liu, Qiang; Yang, Jiandong; Ren, Qinyou; Cao, Wei; Yang, Jingyue; Yu, Zhaocai; Yu, Fang; Wu, Yanlan; Shi, Hengjun; Liu, Wenchao

    2012-01-01

    A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells

  19. Benign breast disease, mammographic breast density, and the risk of breast cancer.

    Science.gov (United States)

    Tice, Jeffrey A; O'Meara, Ellen S; Weaver, Donald L; Vachon, Celine; Ballard-Barbash, Rachel; Kerlikowske, Karla

    2013-07-17

    Benign breast disease and high breast density are prevalent, strong risk factors for breast cancer. Women with both risk factors may be at very high risk. We included 42818 women participating in the Breast Cancer Surveillance Consortium who had no prior diagnosis of breast cancer and had undergone at least one benign breast biopsy and mammogram; 1359 women developed incident breast cancer in 6.1 years of follow-up (78.1% invasive, 21.9% ductal carcinoma in situ). We calculated hazard ratios (HRs) using Cox regression analysis. The referent group was women with nonproliferative changes and average density. All P values are two-sided. Benign breast disease and breast density were independently associated with breast cancer. The combination of atypical hyperplasia and very high density was uncommon (0.6% of biopsies) but was associated with the highest risk for breast cancer (HR = 5.34; 95% confidence interval [CI] = 3.52 to 8.09, P < .001). Proliferative disease without atypia (25.6% of biopsies) was associated with elevated risk that varied little across levels of density: average (HR = 1.37; 95% CI = 1.11 to 1.69, P = .003), high (HR = 2.02; 95% CI = 1.68 to 2.44, P < .001), or very high (HR = 2.05; 95% CI = 1.54 to 2.72, P < .001). Low breast density (4.5% of biopsies) was associated with low risk (HRs <1) for all benign pathology diagnoses. Women with high breast density and proliferative benign breast disease are at very high risk for future breast cancer. Women with low breast density are at low risk, regardless of their benign pathologic diagnosis.

  20. Night shift work and prolactin as a breast cancer risk factor

    Directory of Open Access Journals (Sweden)

    Agnieszka Bukowska

    2013-04-01

    Full Text Available Prolactin - a hormone secreted in a circadian rhythm acts as a regulator of growth and development of the mammary glands. It has been observed that working at night increases breast cancer risk in women. Night shift work, probably carcinogenic to humans (Group 2A IARC, can disrupt a circadian rhythm, and thus potentially alter the rhythm of prolactin secretion. The aim of our work was to review epidemiological evidence on the association between prolactin and the risk of breast cancer and the influence of work at night on prolactin secretion. Search was done in the Medline database by keywords (shift work, work at night, risk of breast cancer and prolactin. The increased proliferation of breast cells activated by prolactin can promote the development of cancer. The results of the largest epidemiological prospective studies suggest the association between prolactin levels and the risk of breast cancer in women. So far, only seven studies have investigated the association between work at night and prolactin secretion. In three studies lower concentrations of prolactin have been observed in night shift workers. No relationship between the night shift work duration and prolactin level in women have been reported. Night shift work can modify the profile of prolactin secretion in night workers, probably decreasing the secretion of this hormone at night. It is therefore unlikely that prolactin plays an important role in the development of breast cancer in women working at night. This conclusion is based on the results of a few epidemiological studies. Med Pr 2013;64(2:245–257

  1. Anandamide inhibits adhesion and migration of breast cancer cells

    International Nuclear Information System (INIS)

    Grimaldi, Claudia; Pisanti, Simona; Laezza, Chiara; Malfitano, Anna Maria; Santoro, Antonietta; Vitale, Mario; Caruso, Maria Gabriella; Notarnicola, Maria; Iacuzzo, Irma; Portella, Giuseppe; Di Marzo, Vincenzo; Bifulco, Maurizio

    2006-01-01

    The endocannabinoid system regulates cell proliferation in human breast cancer cells. We reasoned that stimulation of cannabinoid CB 1 receptors could induce a non-invasive phenotype in breast mtastatic cells. In a model of metastatic spreading in vivo, the metabolically stable anandamide analogue, 2-methyl-2'-F-anandamide (Met-F-AEA), significantly reduced the number and dimension of metastatic nodes, this effect being antagonized by the selective CB 1 antagonist SR141716A. In MDA-MB-231 cells, a highly invasive human breast cancer cell line, and in TSA-E1 cells, a murine breast cancer cell line, Met-F-AEA inhibited adhesion and migration on type IV collagen in vitro without modifying integrin expression: both these effects were antagonized by SR141716A. In order to understand the molecular mechanism involved in these processes, we analyzed the phosphorylation of FAK and Src, two tyrosine kinases involved in migration and adhesion. In Met-F-AEA-treated cells, we observed a decreased tyrosine phosphorylation of both FAK and Src, this effect being attenuated by SR141716A. We propose that CB 1 receptor agonists inhibit tumor cell invasion and metastasis by modulating FAK phosphorylation, and that CB 1 receptor activation might represent a novel therapeutic strategy to slow down the growth of breast carcinoma and to inhibit its metastatic diffusion in vivo

  2. [Hormonotherapy for breast cancer prevention: What about women with genetic predisposition to breast cancer?].

    Science.gov (United States)

    Sénéchal, Claire; Reyal, Fabien; Callet, Nasrine; This, Pascale; Noguès, Catherine; Stoppa-Lyonnet, Dominique; Fourme, Emmanuelle

    2016-03-01

    In France, women carrying BRCA1/2 mutation, at an identified high risk of breast cancer are recommended to undergo breast MRI screening. That screening does not however prevent the risk of developing a breast cancer. The only alternative to breast cancer screening available in France is surgical prevention by prophylactic mastectomy. An interesting option for women who wish to reduce their breast cancer risk, but are unready for prophylactic mastectomy is a preventive hormonal treatment by aromatase inhibitors, or selective estrogens receptor modulators (SERMs). Reliable clinical trials show the efficiency of tamoxifen, raloxifen, exemestane, and anastrozole especially, in reducing breast cancer incidence by 33%, 34%, 65% and 53% respectively. This article tries to sum up the main published trials of breast cancer prevention with hormonal treatment, and presents the latest American and English clinical guidelines concerning hormonal prevention for women at high risk of breast cancer, and starts thinking about the possibilities of hormonoprevention, especially among women carrying a BRCA1/2 mutation in France. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  3. Suppression of SOX18 by siRNA inhibits cell growth and invasion of breast cancer cells.

    Science.gov (United States)

    Zhang, Jianxiang; Ma, Yanmei; Wang, Shoujun; Chen, Fu; Gu, Yuanting

    2016-06-01

    Breast cancer is the most common malignancy in women around the world, and its incidence and mortality rates are still rising. An increasing number of studies have reported that SOX18 plays an important role in various cancers. However, the role of SOX18 in breast cancer remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of SOX18 in breast cancer. We found that the mRNA and protein expression levels of SOX18 were prevalently and significantly overexpressed in human breast cancer cell lines. Next, we performed loss-of-function experiments by transfection of two breast cancer cell lines, BT-474 and MCF-7, with SOX18 small interfering RNAs (siRNA). Results showed that SOX18 siRNA transfection significantly suppressed mRNA and protein expression of SOX18 in breast cancer cells. Furthermore, knockdown of SOX18 significantly inhibited cell proliferation and invasion, but promoted apoptosis in breast cancer cells. Importantly, several oncogenic proteins, including the Ras homolog gene family member A (RhoA), platelet-derived growth factor B (PDGFB), Insulin-like growth factor 1 receptor (IGF-1R), and matrix metalloproteinase-7 (MMP-7), were markedly decreased by SOX18 siRNA. Taken together, the results of our study suggest that knockdown of SOX18 inhibits breast cancer cell growth and invasion, possibly by downregulating downstream oncogenic proteins, providing novel insights into the development of breast cancer therapy through targeting of SOX18.

  4. Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

    International Nuclear Information System (INIS)

    Lazarus, Kyren A.; Zhao, Zhe; Knower, Kevin C.; To, Sarah Q.; Chand, Ashwini L.; Clyne, Colin D.

    2013-01-01

    Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E 2 ), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E 2 , showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E 2 treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer

  5. Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Lazarus, Kyren A. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Environmental and Biotechnology Centre, Swinburne University, Hawthorn, Victoria 3122 (Australia); Zhao, Zhe; Knower, Kevin C. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); To, Sarah Q. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia); Chand, Ashwini L. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Clyne, Colin D., E-mail: Colin.clyne@princehenrys.org [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia)

    2013-08-30

    Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E{sub 2}), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E{sub 2}, showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E{sub 2} treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer.

  6. Metabolic Syndrome and Breast Cancer Risk.

    Science.gov (United States)

    Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

    2017-01-01

    The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

  7. Improved detection of breast cancer on FDG-PET cancer screening using breast positioning device

    International Nuclear Information System (INIS)

    Kaida, Hayato; Ishibashi, Masatoshi; Fujii, Teruhiko; Kurata, Seiji; Ogo, Etsuyo; Hayabuchi, Naofumi; Tanaka, Maki

    2008-01-01

    The aim of this study was to investigate the detection rate of breast cancer by positron emission tomography cancer screening using a breast positioning device. Between January 2004 and January 2006, 1,498 healthy asymptomatic individuals underwent cancer screening by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) at our institution; 660 of 1498 asymptomatic healthy women underwent breast PET imaging in the prone position using the breast positioning device to examine the mammary glands in addition to whole-body PET imaging. All subjects that showed abnormal 18 F-FDG uptake in the mammary glands were referred for further examination or surgery at our institution or a local hospital. Our data were compared with the histopathological findings or findings of other imaging modalities in our institution and replies from the doctors at another hospital. Of the 660 participants, 7 (1.06%) were found to have breast cancers at a curable stage. All the seven cancers were detected by breast PET imaging, but only five of these were detected by whole-body PET imaging; the other two were detected by breast PET imaging using the breast positioning device. In cancer screening, prone breast imaging using a positioning device may help to improve the detection rate of breast cancer. However, overall cancer including mammography and ultrasonography screening should be performed to investigate the false-negative cases and reduce false-positive cases. The effectiveness of prone breast PET imaging in cancer screening should be investigated using a much larger number of cases in the near future. (author)

  8. Early Diagnosis of Breast Cancer.

    Science.gov (United States)

    Wang, Lulu

    2017-07-05

    Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.

  9. Disturbance of Mammary UDP-Glucuronosyltransferase Represses Estrogen Metabolism and Exacerbates Experimental Breast Cancer.

    Science.gov (United States)

    Zhou, Xueyan; Zheng, Ziqiang; Xu, Chang; Wang, Juan; Min, Mengjun; Zhao, Yun; Wang, Xi; Gong, Yinhan; Yin, Jiale; Guo, Meng; Guo, Dong; Zheng, Junnian; Zhang, Bei; Yin, Xiaoxing

    2017-08-01

    The progression of breast cancer is closely related to the levels of estrogens within the body. UDP-glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying steroid hormone. In the present study, we aim at uncovering the potential dysregulation pattern of UGT and its role in estrogen metabolism and in the pathogenesis of breast cancer. Female Sprague-Dawley rats were treated with 100 mg/kg dimethylbenz(a)anthracene (DMBA) to induce breast cancer. Our results showed that the expression and activity of UGT in mammary tissues were downregulated significantly in DMBA rats. Consistent with this, levels of estradiol, 4-hydroxylated estradiol, and 2-hydroxylated estradiol were increased in both mammary tissues and serum, supporting a notable accumulation of toxic estrogen species in the target tissue of breast cancer. In addition, we also observed the decreased cell migration, cell proliferation, and DNA damage in UGT-transfected MCF-7 cells, suggesting a protective role of UGT against estrogen-induced mammary carcinogenesis. Taken together, these results indicated that accumulation of estrogens induced by UGT deficiency is a critical factor to induce the development of breast cancer. UGT contributes to estrogen elimination, and its glucuronidation capacity influences the estrogen signaling pathway and the pathogenesis of breast cancer. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. Amplified in Breast Cancer Regulates Transcription and Translation in Breast Cancer Cells.

    Science.gov (United States)

    Ochnik, Aleksandra M; Peterson, Mark S; Avdulov, Svetlana V; Oh, Annabell S; Bitterman, Peter B; Yee, Douglas

    2016-02-01

    Control of mRNA translation is fundamentally altered in cancer. Insulin-like growth factor-I (IGF-I) signaling regulates key translation mediators to modulate protein synthesis (e.g. eIF4E, 4E-BP1, mTOR, and S6K1). Importantly the Amplified in Breast Cancer (AIB1) oncogene regulates transcription and is also a downstream mediator of IGF-I signaling. To determine if AIB1 also affects mRNA translation, we conducted gain and loss of AIB1 function experiments in estrogen receptor alpha (ERα)(+) (MCF-7L) and ERα(-) (MDA-MB-231, MDA-MB-435 and LCC6) breast cancer cells. AIB1 positively regulated IGF-I-induced mRNA translation in both ERα(+) and ERα(-) cells. Formation of the eIF4E-4E-BP1 translational complex was altered in the AIB1 ERα(+) and ERα(-) knockdown cells, leading to a reduction in the eIF4E/4E-BP1 and eIF4G/4E-BP1 ratios. In basal and IGF-I stimulated MCF-7 and LCC6 cells, knockdown of AIB1 decreased the integrity of the cap-binding complex, reduced global IGF-I stimulated polyribosomal mRNA recruitment with a concomitant decrease in ten of the thirteen genes tested in polysome-bound mRNAs mapping to proliferation, cell cycle, survival, transcription, translation and ribosome biogenesis ontologies. Specifically, knockdown of AIB1 decreased ribosome-bound mRNA and steady-state protein levels of the transcription factors ERα and E2F1 in addition to reduced ribosome-bound mRNA of the ribosome biogenesis factor BYSL in a cell-line specific manner to regulate mRNA translation. The oncogenic transcription factor AIB1 has a novel role in the regulation of polyribosome recruitment and formation of the translational complex. Combinatorial therapies targeting IGF signaling and mRNA translation in AIB1 expressing breast cancers may have clinical benefit and warrants further investigation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  12. Breast cancer screening

    International Nuclear Information System (INIS)

    Vandenbroucke, A.

    1987-01-01

    Many studies have shown that breast cancer screening is able to reduce breast cancer mortality, including the HIP study, the Swedish Trial and the Netherlands studies. Mammography is considered as the most effective method for breast cancer screening but it might be unfeasible for some reasons: - the population acceptability of the method might be low. Indeed, most populations of the South of Europe are less compliant to mass screening than populations of the North of Europe; - the medical equipment and personnel - radiologists and pathologists - might be insufficient; - it might be too costly for the National Health Service, specially where the incidence rate of breast cancer is relatively low (i.e. Greece, Portugal). The validity of screening tests is judged by their sensitivity and their specificity

  13. Breast cancer screening with digital breast tomosynthesis.

    Science.gov (United States)

    Skaane, Per

    2017-01-01

    To give an overview of studies comparing full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in breast cancer screening. The implementation of tomosynthesis in breast imaging is rapidly increasing world-wide. Experimental clinical studies of relevance for DBT screening have shown that tomosynthesis might have a great potential in breast cancer screening, although most of these retrospective reading studies are based on small populations, so that final conclusions are difficult to draw from individual reports. Several retrospective studies and three prospective trials on tomosynthesis in breast cancer screening have been published so far, confirming the great potential of DBT in mammography screening. The main results of these screening studies are presented. The retrospective screening studies from USA have all shown a significant decrease in the recall rate using DBT as adjunct to mammography. Most of these studies have also shown an increase in the cancer detection rate, and the non-significant results in some studies might be explained by a lack of statistical power. All the three prospective European trials have shown a significant increase in the cancer detection rate. The retrospective and the prospective screening studies comparing FFDM and DBT have all demonstrated that tomosynthesis has a great potential for improving breast cancer screening. DBT should be regarded as a better mammogram that could improve or overcome limitations of the conventional mammography, and tomosynthesis might be considered as the new technique in the next future of breast cancer screening.

  14. Breast cancer Ki67 expression preoperative discrimination by DCE-MRI radiomics features

    Science.gov (United States)

    Ma, Wenjuan; Ji, Yu; Qin, Zhuanping; Guo, Xinpeng; Jian, Xiqi; Liu, Peifang

    2018-02-01

    To investigate whether quantitative radiomics features extracted from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are associated with Ki67 expression of breast cancer. In this institutional review board approved retrospective study, we collected 377 cases Chinese women who were diagnosed with invasive breast cancer in 2015. This cohort included 53 low-Ki67 expression (Ki67 proliferation index less than 14%) and 324 cases with high-Ki67 expression (Ki67 proliferation index more than 14%). A binary-classification of low- vs. high- Ki67 expression was performed. A set of 52 quantitative radiomics features, including morphological, gray scale statistic, and texture features, were extracted from the segmented lesion area. Three most common machine learning classification methods, including Naive Bayes, k-Nearest Neighbor and support vector machine with Gaussian kernel, were employed for the classification and the least absolute shrink age and selection operator (LASSO) method was used to select most predictive features set for the classifiers. Classification performance was evaluated by the area under receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity. The model that used Naive Bayes classification method achieved the best performance than the other two methods, yielding 0.773 AUC value, 0.757 accuracy, 0.777 sensitivity and 0.769 specificity. Our study showed that quantitative radiomics imaging features of breast tumor extracted from DCE-MRI are associated with breast cancer Ki67 expression. Future larger studies are needed in order to further evaluate the findings.

  15. Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells.

    Science.gov (United States)

    Fang, Feng; Zheng, Jiamao; Galbaugh, Traci L; Fiorillo, Alyson A; Hjort, Elizabeth E; Zeng, Xianke; Clevenger, Charles V

    2010-06-01

    The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB knockdown with two independent siRNAs was shown to impair PRL-induced reporter expression in breast cancer cell line. cDNA microarray analysis was performed on these cells to assess the effect of CypB reduction, and revealed a significant decrease in PRL-induced endogenous gene expression in two breast cancer cell lines. Parallel functional assays revealed corresponding alterations of both anchorage-independent cell growth and cell motility of breast cancer cells. Our results demonstrate that CypB expression levels significantly modulate PRL-induced function in breast cancer cells ultimately resulting in enhanced levels of PRL-responsive gene expression, cell growth, and migration. Given the increasingly appreciated role of PRL in the pathogenesis of breast cancer, the actions of CypB detailed here are of biological significance.

  16. Breast Cancer Rates by State

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English (US) Español (Spanish) ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  17. Propranolol and survival from breast cancer

    DEFF Research Database (Denmark)

    Cardwell, Chris R; Pottegård, Anton; Vaes, Evelien

    2016-01-01

    BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all......-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all......-analysis techniques. Dose-response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis. RESULTS: The combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all...

  18. A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions

    Science.gov (United States)

    Zhu, Wei; Castro, Nathan J.; Cui, Haitao; Zhou, Xuan; Boualam, Benchaa; McGrane, Robert; Glazer, Robert I.; Zhang, Lijie Grace

    2016-08-01

    Bone metastasis is one of the most prevalent complications of late-stage breast cancer, in which the native bone matrix components, including osteoblasts, are intimately involved in tumor progression. The development of a successful in vitro model would greatly facilitate understanding the underlying mechanism of breast cancer bone invasion as well as provide a tool for effective discovery of novel therapeutic strategies. In the current study, we fabricated a series of in vitro bone matrices composed of a polyethylene glycol hydrogel and nanocrystalline hydroxyapatite of varying concentrations to mimic the native bone microenvironment for the investigation of breast cancer bone metastasis. A stereolithography-based three-dimensional (3D) printer was used to fabricate the bone matrices with precisely controlled architecture. The interaction between breast cancer cells and osteoblasts was investigated in the optimized bone matrix. Using a Transwell® system to separate the two cell lines, breast cancer cells inhibited osteoblast proliferation, while osteoblasts stimulated breast cancer cell growth, whereas, both cell lines increased IL-8 secretion. Breast cancer cells co-cultured with osteoblasts within the 3D bone matrix formed multi-cellular spheroids in comparison to two-dimensional monolayers. These findings validate the use of our 3D printed bone matrices as an in vitro metastasis model, and highlights their potential for investigating breast cancer bone metastasis.

  19. Characterization of TRPS1 and ERAS as oncogenes implicated in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Gonzalez, L.

    2015-07-01

    New high throughput technologies have made possible to identify putative oncogenes in breast cancer. In this project we aim to relate and characterise two novel putative oncogenes, ERAS and TRPS1, in their role in human breast cancer. TRPS1, an atypical GATA factor, modulates cell proliferation and controls cell cycle progression through repression of GATA-regulated genes, therefore acting as a tumour suppressor gene. Conversely, TRPS1 expression has been shown to be significantly elevated in luminal and in a lesser extent in basal breast cancer cells, presenting roles both as an oncogene and as a tumour suppressor gene in breast cancer development. The aim of this project is therefore to determine the characteristics of TRPS1 either as a putative novel human oncogene or as a tumour suppressor gene in breast cancer cells. To this aim, we have cloned a novel isoform of TRPS1 and introduced it into several breast cancer cell lines. Our results show that overexpression of this isoform of TRPS1 results in variations in motility in non-carcinogenic cell lines, as well as in a series of EMT-like changes such as the down-regulation of the EMT marker E-cadherin, both of which can be associated to an increase in malignancy, suggesting an oncogenic behaviour for TRPS1. Furthermore, our results suggest that constitutively active members of the RAS protein family induce the expression of TRPS1, establishing a relationship between both genes. We can conclude that the effects of TRPS1 overexpression are moderate, inducing some changes but not fully transforming the cells. Therefore we cannot confirm that TRPS1 is a putative oncogene in breast cancer. (Author)

  20. Breast Cancer in Men

    Science.gov (United States)

    ... ultrasound or a breast MRI cannot rule out breast cancer then you will need a biopsy to confirm diagnosis. If diagnosed When first diagnosed with breast cancer, many men are in shock. After all, ...

  1. Modeling triple-negative breast cancer heterogeneity: effects of stromal macrophages, fibroblasts and tumor vasculature.

    Science.gov (United States)

    Norton, Kerri-Ann; Jin, Kideok; Popel, Aleksander S

    2018-05-08

    A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells. In vivo studies also demonstrated that blocking signaling of selected secreted factors inhibits tumor growth and metastasis in mouse xenograft models. We investigate the influences of increased migration and proliferation rates on tumor growth, the effect of the presence on fibroblasts or macrophages on growth and morphology, and the contributions of macrophage infiltration on tumor growth. We find that while the presence of macrophages increases overall tumor growth, the increase in macrophage infiltration does not substantially increase tumor growth and can even stifle tumor growth at excessive rates. Copyright © 2018. Published by Elsevier Ltd.

  2. Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To DNA Mutations.

    Science.gov (United States)

    Gómez-Flores-Ramos, Liliana; Castro-Sánchez, Andrea; Peña-Curiel, Omar; Mohar-Betancourt, Alejandro

    2017-01-01

    Young women with breast cancer (YWBC) represent roughly 15% of breast cancer (BC) cases in Latin America and other developing regions. Breast tumors occurring at an early age are more aggressive and have an overall worse prognosis compared to breast tumors in postmenopausal women. The expression of relevant proliferation biomarkers such as endocrine receptors and human epidermal growth factor receptor 2 appears to be unique in YWBC. Moreover, histopathological, molecular, genetic, and genomic studies have shown that YWBC exhibit a higher frequency of aggressive subtypes, differential tumor gene expression, increased genetic susceptibility, and specific genomic signatures, compared to older women with BC. This article reviews the current knowledge on tumor biology and genomic signatures in YWBC.

  3. Risk of primary non-breast cancer after female breast cancer by age at diagnosis

    DEFF Research Database (Denmark)

    Mellemkjær, Lene; Christensen, Jane; Frederiksen, Kirsten Skovsgaard

    2011-01-01

    Women diagnosed with breast cancer at young age have been shown to be at higher risk of developing a new primary cancer than women diagnosed at older ages, but little is known about whether adjustment for calendar year of breast cancer diagnosis, length of follow-up, and/or breast cancer treatment...

  4. Freund's vaccine adjuvant promotes Her2/Neu breast cancer

    International Nuclear Information System (INIS)

    Cotroneo, Michelle S; Haag, Jill D; Stapel, Nicholas R; Waller, Jordy L; Woditschka, Stephan; Gould, Michael N

    2009-01-01

    Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene. The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed. Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis. Our data suggests that systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer

  5. Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes.

    Directory of Open Access Journals (Sweden)

    I-Hsuan Lin

    Full Text Available Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs and the hypomethylation of the megabase-sized partially methylated domains (PMDs are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation.

  6. Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

    Science.gov (United States)

    Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

    2014-10-01

    The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

  7. G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis.

    Directory of Open Access Journals (Sweden)

    Matthew J Billard

    Full Text Available Triple negative breast cancer (TNBC is a heterogeneous disease that has a poor prognosis and limited treatment options. Chemokine receptor interactions are important modulators of breast cancer metastasis; however, it is now recognized that quantitative surface expression of one important chemokine receptor, CXCR4, may not directly correlate with metastasis and that its functional activity in breast cancer may better inform tumor pathogenicity. G protein coupled receptor kinase 3 (GRK3 is a negative regulator of CXCR4 activity, and we show that GRK expression correlates with tumorigenicity, molecular subtype, and metastatic potential in human tumor microarray analysis. Using established human breast cancer cell lines and an immunocompetent in vivo mouse model, we further demonstrate that alterations in GRK3 expression levels in tumor cells directly affect migration and invasion in vitro and the establishment of distant metastasis in vivo. The effects of GRK3 modulation appear to be specific to chemokine-mediated migration behaviors without influencing tumor cell proliferation or survival. These data demonstrate that GRK3 dysregulation may play an important part in TNBC metastasis.

  8. G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis

    Science.gov (United States)

    Billard, Matthew J.; Fitzhugh, David J.; Parker, Joel S.; Brozowski, Jaime M.; McGinnis, Marcus W.; Timoshchenko, Roman G.; Serafin, D. Stephen; Lininger, Ruth; Klauber-Demore, Nancy; Sahagian, Gary; Truong, Young K.; Sassano, Maria F.; Serody, Jonathan S.; Tarrant, Teresa K.

    2016-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous disease that has a poor prognosis and limited treatment options. Chemokine receptor interactions are important modulators of breast cancer metastasis; however, it is now recognized that quantitative surface expression of one important chemokine receptor, CXCR4, may not directly correlate with metastasis and that its functional activity in breast cancer may better inform tumor pathogenicity. G protein coupled receptor kinase 3 (GRK3) is a negative regulator of CXCR4 activity, and we show that GRK expression correlates with tumorigenicity, molecular subtype, and metastatic potential in human tumor microarray analysis. Using established human breast cancer cell lines and an immunocompetent in vivo mouse model, we further demonstrate that alterations in GRK3 expression levels in tumor cells directly affect migration and invasion in vitro and the establishment of distant metastasis in vivo. The effects of GRK3 modulation appear to be specific to chemokine-mediated migration behaviors without influencing tumor cell proliferation or survival. These data demonstrate that GRK3 dysregulation may play an important part in TNBC metastasis. PMID:27049755

  9. Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

    International Nuclear Information System (INIS)

    Hsieh, Szu-Min; Smith, Robert A; Lintell, Nicholas A; Hunter, Kent W; Griffiths, Lyn R

    2009-01-01

    The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1) underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP) protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S) to Phe (F)) changes a hydrophilic residue (S) to a hydrophobic residue (F) and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5' near gene), and rs746429 (synonymous (Ala (A) to Ala (A

  10. Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Lintell Nicholas A

    2009-09-01

    Full Text Available Abstract Background The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1 underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. Methods The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. Conclusion This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S to Phe (F changes a hydrophilic residue (S to a hydrophobic residue (F and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5

  11. Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

    Science.gov (United States)

    Duffy, Stephen W; Morrish, Oliver W E; Allgood, Prue C; Black, Richard; Gillan, Maureen G C; Willsher, Paula; Cooke, Julie; Duncan, Karen A; Michell, Michael J; Dobson, Hilary M; Maroni, Roberta; Lim, Yit Y; Purushothaman, Hema N; Suaris, Tamara; Astley, Susan M; Young, Kenneth C; Tucker, Lorraine; Gilbert, Fiona J

    2018-01-01

    Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1-5%) increase in risk per 10 cm 3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Contralateral breast cancer risk

    International Nuclear Information System (INIS)

    Unnithan, Jaya; Macklis, Roger M.

    2001-01-01

    The use of breast-conserving treatment approaches for breast cancer has now become a standard option for early stage disease. Numerous randomized studies have shown medical equivalence when mastectomy is compared to lumpectomy followed by radiotherapy for the local management of this common problem. With an increased emphasis on patient involvement in the therapeutic decision making process, it is important to identify and quantify any unforeseen risks of the conservation approach. One concern that has been raised is the question of radiation- related contralateral breast cancer after breast radiotherapy. Although most studies do not show statistically significant evidence that patients treated with breast radiotherapy are at increased risk of developing contralateral breast cancer when compared to control groups treated with mastectomy alone, there are clear data showing the amount of scattered radiation absorbed by the contralateral breast during a routine course of breast radiotherapy is considerable (several Gy) and is therefore within the range where one might be concerned about radiogenic contralateral tumors. While radiation related risks of contralateral breast cancer appear to be small enough to be statistically insignificant for the majority of patients, there may exist a smaller subset which, for genetic or environmental reasons, is at special risk for scatter related second tumors. If such a group could be predicted, it would seem appropriate to offer either special counselling or special prevention procedures aimed at mitigating this second tumor risk. The use of genetic testing, detailed analysis of breast cancer family history, and the identification of patients who acquired their first breast cancer at a very early age may all be candidate screening procedures useful in identifying such at- risk groups. Since some risk mitigation strategies are convenient and easy to utilize, it makes sense to follow the classic 'ALARA' (as low as reasonably

  13. Radiologic aspects of breast cancers detected through a breast cancer screening program

    International Nuclear Information System (INIS)

    Azavedo, E.; Svane, G.

    1991-01-01

    Early detection in breast cancer and reduced mortality in women with this disease is today attributed to widespread use of mammography. High-quality performance is essential in all steps of breast cancer screening programs in order to avoid unnecessary anxiety and surgery in the women concerned. This report presents radiologic aspects of screening cancers. A total of 8370 asymptomatic women aged 50-69 years were screened with 2-view mammography, of which only 70 (0.84 percent) were selected for surgery after a thorough work-up. Cancers were verified histologically in 61 women and 9 showed non-malignant histology, giving a cancer detection rate of 7.3 cancers per thousand screened asymptomatic women. The benign/malignant ratio in the operated cases is thus approximately 1:7. The cancers detected showed all existing types of mammographic features where 77 percent (47 cases) showed rather typical findings, such as spiculated densities both with and without microcalcifications. The results indicate that surgery can be minimized without impairing the breast cancer detection rate. Radiologists in screening programs should be aware that a large proportion of non-palpable breast cancers present in rather unconventional forms. This point is important in order to maintain a high cancer detection rate and thereby justify the widespread use of mammography as a screening tool for breast cancer in asymptomatic women. (author). 20 refs.; 1 tab

  14. Breast cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  15. Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer.

    Science.gov (United States)

    Park, Jeenah; Thomas, Scott; Zhong, Allison Y; Wolfe, Alan R; Krings, Gregor; Terranova-Barberio, Manuela; Pawlowska, Nela; Benet, Leslie Z; Munster, Pamela N

    2018-01-08

    Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.

  16. Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xuchen Cao; Bowen Liu; Wenfeng Cao; Weiran Zhang; Fei Zhang; Hongmeng Zhao; Ran Meng

    2013-01-01

    Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables.The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated.Cell proliferation and viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays.Flow cytometry,fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy,and the role of autophagy was assessed using autophagy inhibitors.Apigenin dose-and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines.The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3,PARP cleavage and Bax/Bcl-2 ratios.The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis.In addition,the apigenin-treated cells exhibited autophagy,as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles (AVOs)by flow cytometry.Furthermore,the results of the Western blot analysis revealed that the level of LC3-Ⅱ,the processed form of LC3-Ⅰ,was increased.Treatment with the autophagy inhibitor,3-methyladenine (3-MA),significantly enhanced the apoptosis induced by apigenin,which was accompanied by an increase in the level of PARP cleavage.Similar results were also confirmed by flow cytometry and fluorescence microscopy.These results indicate that apigenin has apoptosis-and autophagy-inducing effects in breast cancer cells.Autophagy plays a cyto-protective role in apigenin-induced apoptosis,and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.

  17. Targeted Therapy for Breast Cancer Prevention

    Science.gov (United States)

    den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

    2013-01-01

    With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

  18. Correlation of MRI apparent diffusion coefficient of invasive breast cancer with tumor tissue growth and angiogenesis

    Directory of Open Access Journals (Sweden)

    Ze-Hong Fu

    2017-08-01

    Full Text Available Objective: To study the correlation of MRI apparent diffusion coefficient (ADC value of invasive breast cancer with tumor tissue growth and angiogenesis. Methods: Patients with breast mass who were treated in Wuhan No. 6 Hospital between March 2014 and May 2017 were selected as the research subjects and divided into group A with invasive ductal carcinoma, group B with intraductal carcinoma and group C with benign lesion according to the biopsy results, magnetic resonance diffusion-weighted imaging was conducted to determine ADC values, and biopsy tissue was taken to determine the expression of proliferation genes and angiogenesis genes. Results: USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A and group B were significantly higher than those of group C while ADC value as well as ALEX1 and Bax protein expression levels were significantly lower than those of group C; USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A were significantly higher than those of group B while ADC value as well as ALEX1 and Bax protein expression levels was significantly lower than those of group B; USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in invasive breast cancer tissue with high ADC value were significantly lower than those in invasive breast cancer tissue with low ADC value while ALEX1 and Bax protein expression levels were significantly higher than those in invasive breast cancer tissue with low ADC value. Conclusion: The decrease of ADC value of invasive breast cancer is closely related to cancer cell proliferation and angiogenesis.

  19. Hormone Therapy for Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... sensitive breast cancer cells contain proteins called hormone receptors that become activated when hormones bind to them. ...

  20. Ultrasound screening of contralateral breast after surgery for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Ja [Department of Radiology, Seoul Metropolitan Government Seoul National University, Boramae Medical Center (Korea, Republic of); Chung, Se-Yeong; Chang, Jung Min; Cho, Nariya [Department of Radiology, Seoul National University Hospital (Korea, Republic of); Han, Wonshik [Department of Surgery, Seoul National University Hospital (Korea, Republic of); Moon, Woo Kyung, E-mail: moonwk@snu.ac.kr [Department of Radiology, Seoul National University Hospital (Korea, Republic of)

    2015-01-15

    Highlights: • The addition of supplemental US to mammography depicted additional 5.0 cancers per 1000 postoperative women. • Positive biopsy rate of mammography-detected lesions was 66.7% (4 of 6) and that of US-detected lesions was 40.0% (6 of 15). • US can be helpful to detect mammographically occult breast cancer in the contralateral breast in women with previous history of cancer and dense breast. - Abstract: Objective: To determine whether supplemental screening ultrasound (US) to mammography could improve cancer detection rate of the contralateral breast in patients with a personal history of breast cancer and dense breasts. Materials and methods: During a one-year study period, 1314 screening patients with a personal history of breast cancer and dense breasts simultaneously underwent mammography and breast US. BI-RADS categories were given for mammography or US-detected lesions in the contralateral breast. The reference standard was histology and/or 1-year imaging follow-up, and the cancer rate according to BI-RADS categories and cancer detection rate and positive biopsy rate according to detection modality were analyzed. Results: Of 1314 patients, 84 patients (6.4%) were categorized as category 3 with one interval cancer and one cancer which was upgraded to category 4A after 6-month follow-up US (2.5% cancer rate, 95% CIs 1.5–9.1%). Fifteen patients (1.1%) had category 4A or 4B lesions in the contralateral breast. Four lesions were detected on mammography (two lesions were also visible on US) and 11 lesions were detected on US and 5 cancers were confirmed (33.3%, 95% CIs 15.0–58.5%). Six patients (0.5%) had category 4C lesions, 2 detected on mammography and 4 on US and 4 cancers were confirmed (66.7%, 95% CIs 29.6–90.8%). No lesions were categorized as category 5 in the contralateral breast. Cancer detection rate by mammography was 3.3 per 1000 patients and that by US was 5.0 per 1000 patients, therefore overall cancer detection rate by

  1. Ultrasound screening of contralateral breast after surgery for breast cancer

    International Nuclear Information System (INIS)

    Kim, Seung Ja; Chung, Se-Yeong; Chang, Jung Min; Cho, Nariya; Han, Wonshik; Moon, Woo Kyung

    2015-01-01

    Highlights: • The addition of supplemental US to mammography depicted additional 5.0 cancers per 1000 postoperative women. • Positive biopsy rate of mammography-detected lesions was 66.7% (4 of 6) and that of US-detected lesions was 40.0% (6 of 15). • US can be helpful to detect mammographically occult breast cancer in the contralateral breast in women with previous history of cancer and dense breast. - Abstract: Objective: To determine whether supplemental screening ultrasound (US) to mammography could improve cancer detection rate of the contralateral breast in patients with a personal history of breast cancer and dense breasts. Materials and methods: During a one-year study period, 1314 screening patients with a personal history of breast cancer and dense breasts simultaneously underwent mammography and breast US. BI-RADS categories were given for mammography or US-detected lesions in the contralateral breast. The reference standard was histology and/or 1-year imaging follow-up, and the cancer rate according to BI-RADS categories and cancer detection rate and positive biopsy rate according to detection modality were analyzed. Results: Of 1314 patients, 84 patients (6.4%) were categorized as category 3 with one interval cancer and one cancer which was upgraded to category 4A after 6-month follow-up US (2.5% cancer rate, 95% CIs 1.5–9.1%). Fifteen patients (1.1%) had category 4A or 4B lesions in the contralateral breast. Four lesions were detected on mammography (two lesions were also visible on US) and 11 lesions were detected on US and 5 cancers were confirmed (33.3%, 95% CIs 15.0–58.5%). Six patients (0.5%) had category 4C lesions, 2 detected on mammography and 4 on US and 4 cancers were confirmed (66.7%, 95% CIs 29.6–90.8%). No lesions were categorized as category 5 in the contralateral breast. Cancer detection rate by mammography was 3.3 per 1000 patients and that by US was 5.0 per 1000 patients, therefore overall cancer detection rate by

  2. Efficacy of breast conservation therapy in early stage bilateral breast cancer

    International Nuclear Information System (INIS)

    Lee, Misa M.; Chen, Luci M.; Heimann, Ruth; Powers, Claire; Weichselbaum, Ralph R.

    1996-01-01

    PURPOSE: To evaluate outcome of patients with bilateral breast cancer as compared to unilateral breast cancer treated with breast conservation therapy. This is a complex issue, however, we address this by comparing (1) synchronous bilateral breast cancer patients, (2) metachronous bilateral breast cancer patients from the time of diagnosis of the second breast primary, and (3) unilateral breast cancer patients. The authors recognize that there are inherent biases in these comparisons. MATERIALS AND METHODS: A total of 60 bilateral patients and 1080 unilateral patients treated with breast conservation therapy from 1977-1994 were analyzed for outcome. Of the 60 bilateral patients, 44 were metachronous bilateral breast cancer patients (MBBC) and 16 were synchronous breast cancer patients (SBBC). Patients with bilateral breast cancer had local-regional disease with the following tumor stages: DCIS=8%, T1=80%, T2=12%, pathologic N0=90%, pathologic N+=10%. Unilateral patients had the following tumor stages: DCIS=10%, T1=66%, T2=20%, T3=1.2%, Tx=2%, pathological N0=80%, pathological N+=19%, and NX=1%. The majority of patients received lumpectomy and axillary node dissection followed by radiation therapy. The median size of the lesions were 1.4cm and 1.5cm for bilateral and unilateral patients, respectively. Median total dose to the primary tumor was 60Gy for both unilateral and bilateral patients. Of the 44 metachronous bilateral breast cancer patients, 14 patients received breast conservation for both the first and second lesions while 30 patients had breast conservation for only the second metachronous breast lesion. Thus 58 lesions in the 44 patients were treated with breast conservation therapy in the patients with metachronous bilateral breast cancer. Of the synchronous bilateral breast cancer patients, 13 out of 16 patients had breast conserving therapy for both breasts, and 3 patients received mastectomy for the second synchronous breast tumor. The median follow

  3. Neutralization of TNFα in tumor with a novel nanobody potentiates paclitaxel-therapy and inhibits metastasis in breast cancer.

    Science.gov (United States)

    Ji, Xuemei; Peng, Zhengxin; Li, Xiaorui; Yan, Zhonghui; Yang, Yue; Qiao, Zheng; Liu, Yu

    2017-02-01

    Metastatic disease is the major cause of death from cancer, and immunotherapy and chemotherapy have had limited success in reversing its progression. Researchers have suggested that inflammatory factors in the tumor environment can promote cancer invasion and metastasis, stimulating cancer progression. Thus, novel strategies that target cytokines and modulate the tumor microenvironment may emerge as important approaches for treating metastatic breast cancer. Specific neutralization of pathogenic TNF signaling using a TNFα antibody has gained increasing attention. Considering this, a selective human TNFα neutralized antibody was generated based on nanobody technology. A TNFα-specific nanobody was produced in Pichia pastoris with a molecular mass of 15 kDa and affinity constant of 2.05 nM. In the proliferation experiment, the TNFα nanobody could inhibit the proliferation of the breast cancer cell line MCF-7 induced by hTNFα in a dose-dependent manner. In the microinvasion model, the TNFα nanobody could inhibit the migration of the breast cancer cell lines MCF-7, MDA-MB-231 and the invasiveness of MDA-MB-231 induced by hTNFα in a dose-dependent manner. Drug administration of the combination of paclitaxel with the TNFα nanobody in vivo significantly enhanced the efficacy against 4T-1 breast tumor proliferation and lung metastasis; meanwhile, E-cadherin tumor epithelial marker expression was upregulated, supporting the anti-tumor therapeutic relevance of paclitaxel and the TNFα nanobody on EMT. This study highlights the importance of neutralizing low TNFα levels in the tumor microenvironment to sensitize the chemotherapeutic response, which has attractive potential for clinical applications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Radiation-induced breast cancer

    International Nuclear Information System (INIS)

    Finnerty, N.A.; Buzdar, A.U.; Blumenschein, G.R.

    1984-01-01

    Between 1975 and 1983, sixteen patients with a history of irradiation at an early age to the head, neck, or chest areas for a variety of conditions in whom breast cancer subsequently developed were seen at out institute. The median latent period between the irradiation and the development of breast cancer was 420 months. The distribution of patients by stage of the disease and the median age at diagnosis of this subgroup was similar to the breast cancer observed in the general population. The subsequent course of this disease was also similar to the breast cancer observed in the general population. A substantial number of women have been exposed to irradiation at a young age, and these women are at a higher risk of having breast cancer develop. These women should be closely observed to discover the disease in an early curable stage

  5. Hereditary forms of breast cancer

    International Nuclear Information System (INIS)

    Bella, V.

    2009-01-01

    Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence it occurs in the familial and hereditary form. Persons with the occurrence of positive family anamnesis of breast cancer should be actively investigated. In the indicated cases it is necessary to send the woman to genetic examination. In case that the hereditary form of breast cancer is affirmed it is necessary to examine her family relatives. Women with the hereditary form of breast cancer occur in about 5 – 10 % portion from all women diagnosed with breast cancer. Nowadays we already know that 80 % of hereditary breast cancers are due to germ mutations in BRCA 1 and BRCA 2 gene. Persons with detected gene mutations must be dispensarized in the centres intended for it. (author)

  6. Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer.

    Science.gov (United States)

    Walter, Katherine R; Goodman, Merit L; Singhal, Hari; Hall, Jade A; Li, Tianbao; Holloran, Sean M; Trinca, Gloria M; Gibson, Katelin A; Jin, Victor X; Greene, Geoffrey L; Hagan, Christy R

    2017-10-01

    The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, Interferon (IFN)-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR. Progestin-dependent transcriptional repression of ISGs was observed in breast cancer cell line models and human breast tumors. Ligand-independent regulation of ISGs was also observed, as basal transcript levels were markedly higher in cells with PR knockdown. PR repressed ISG transcription in response to IFN treatment, the canonical mechanism through which these genes are activated. Liganded PR is robustly recruited to enhancer regions of ISGs, and ISG transcriptional repression is dependent upon PR's ability to bind DNA. In response to PR activation, key regulatory transcription factors that are required for IFN-activated ISG transcription, STAT2 and IRF9, exhibit impaired recruitment to ISG promoter regions, correlating with PR/ligand-dependent ISG transcriptional repression. IFN activation is a critical early step in nascent tumor recognition and destruction through immunosurveillance. As the large majority of breast tumors are PR positive at the time of diagnosis, PR-dependent downregulation of IFN signaling may be a mechanism through which early PR-positive breast tumors evade the immune system and develop into clinically relevant tumors. Implications: This study highlights a novel transcriptional mechanism through which PR drives breast cancer development and potentially evades the immune system. Mol Cancer Res; 15(10); 1331-40. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

    OpenAIRE

    Xiu Juan Li; Zhao Jun Ren; Jin Hai Tang; Qiao Yu

    2017-01-01

    Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes a...

  8. Downregulation of CD44 reduces doxorubicin resistance of CD44+CD24- breast cancer cells

    Directory of Open Access Journals (Sweden)

    Phuc PV

    2011-06-01

    Full Text Available Pham Van Phuc, Phan Lu Chinh Nhan, Truong Hai Nhung, Nguyen Thanh Tam, Nguyen Minh Hoang, Vuong Gia Tue, Duong Thanh Thuy, Phan Kim NgocLaboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh, VietnamBackground: Cells within breast cancer stem cell populations have been confirmed to have a CD44+CD24- phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells.Methods: In this study, we reduced CD44 expression in CD44+CD24- breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44+CD24- breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug.Results: The proliferation of CD44 downregulated CD44+CD24- breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups.Conclusions: It would appear that expression of CD44 is integral among the CD44+CD24- cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy.Keywords: antitumor drugs, breast cancer stem cells, CD44, CD44+CD24- cells, doxorubicin

  9. Genetics Home Reference: breast cancer

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Breast cancer Breast cancer Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Breast cancer is a disease in which certain cells in ...

  10. Awareness and current knowledge of breast cancer.

    Science.gov (United States)

    Akram, Muhammad; Iqbal, Mehwish; Daniyal, Muhammad; Khan, Asmat Ullah

    2017-10-02

    Breast cancer remains a worldwide public health dilemma and is currently the most common tumour in the globe. Awareness of breast cancer, public attentiveness, and advancement in breast imaging has made a positive impact on recognition and screening of breast cancer. Breast cancer is life-threatening disease in females and the leading cause of mortality among women population. For the previous two decades, studies related to the breast cancer has guided to astonishing advancement in our understanding of the breast cancer, resulting in further proficient treatments. Amongst all the malignant diseases, breast cancer is considered as one of the leading cause of death in post menopausal women accounting for 23% of all cancer deaths. It is a global issue now, but still it is diagnosed in their advanced stages due to the negligence of women regarding the self inspection and clinical examination of the breast. This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of breast cancer, stages of breast cancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.

  11. Breast cancer patterns and lifetime risk of developing breast cancer among Puerto Rican females.

    Science.gov (United States)

    Nazario, C M; Figueroa-Vallés, N; Rosario, R V

    2000-03-01

    The purpose of this study was to evaluate the epidemiologic patterns of breast cancer and to estimate the lifetime risk probability of developing breast cancer among Hispanic females using cancer data from Puerto Rico. The age-adjusted breast cancer incidence rate (per 100,000) in Puerto Rico increased from 15.3 in 1960-1964 to 43.3 in 1985-1989. The age-adjusted breast cancer mortality rate (per 100,000) increased from 5.7 to 10.6 comparing the same two time periods (1960-1964 vs 1985-1989). Nevertheless, in 1985-1989 breast cancer incidence rate was higher in US White females (110.8 per 100,000) compared to Puerto Rican females (51.4 per 100,000; age-adjusted to the 1970 US standard population). The breast cancer mortality rate was also higher in US White females (27.4 per 100,000) than in Puerto Rican females (15.1 per 100,000; age-adjusted to the 1970 US standard population) during 1985-1989. A multiple decrement life table was constructed applying age-specific incidence and mortality rates from cross-sectional data sets (1980-1984 and 1985-1989 data for Puerto Rican females and 1987-1989 SEER data sets for US White and Black females) to a hypothetical cohort of 10,000,000 women. The probability of developing invasive breast cancer was computed for the three groups using the long version of DEVCAN: Probability of DEVeloping CANcer software, version 3.3. The lifetime risk of developing breast cancer was 5.4% for Puerto Rican females, compared to 8.8% for US Black females and 13.0% for US White females. Lifetime risk for Puerto Rican females increased from 4.5% in 1980-1984 to 5.4% in 1985-1989. Lifetime risk of breast cancer appears to be increasing in Puerto Rico, but remains lower than the probability for US White females. Therefore, the application of lifetime probability of developing invasive breast cancer estimated for the US female population will overestimate the risk for the Puerto Rican female population.

  12. Breast cancer epidemiology and risk factors

    International Nuclear Information System (INIS)

    Broeders, M. J. M.; Verbeek, A. L. M.

    1997-01-01

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form may therefore have more influence on one form of breast cancer than another. So far though, as shown in their summary of current knowledge on established and dubious risk factors, no risk factors have been identified that can explain a major part of the incidence. Efforts to identify other ways for primary prevention have also been discouraging, even though breast cancer is one of the most investigated tumours world-wide. Thus, at this point i time, the most important strategy to reduce breast cancer mortality is early detection through individual counselling and organised breast screening programs. The recent isolation of breast cancer susceptibility genes may introduce new ways to reduce the risk of breast cancer in a small subset of women

  13. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  14. Treatment Option Overview (Breast Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... only hormone therapy after a hysterectomy . Selective estrogen receptor modulators (SERMs). Aromatase inhibitors . Less exposure of breast ...

  15. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2011-10-01

    cells we observed that it promoted transformation of HMLE cells, suggesting a tumor suppressive role of Merlin in breast cancer (Figure 4B). A...08-1-0767 TITLE: Identifying Breast Cancer Oncogenes PRINCIPAL INVESTIGATOR: Yashaswi Shrestha...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-08-1-0767 Identifying Breast Cancer Oncogenes Yashaswi Shrestha Dana-Farber

  16. Breast cancer literacy and health beliefs related to breast cancer screening among American Indian women.

    Science.gov (United States)

    Roh, Soonhee; Burnette, Catherine E; Lee, Yeon-Shim; Jun, Jung Sim; Lee, Hee Yun; Lee, Kyoung Hag

    2018-08-01

    The purpose of this article is to examine the health beliefs and literacy about breast cancer and their relationship with breast cancer screening among American Indian (AI) women. Using the Health Belief Model (HBM) and hierarchical logistic regression with data from a sample of 286 AI female adults residing in the Northern Plains, we found that greater awareness of breast cancer screening was linked to breast cancer screening practices. However, perceived barriers, one of the HBM constructs, prevented such screening practices. This study suggested that culturally relevant HBM factors should be targeted when developing culturally sensitive breast cancer prevention efforts.

  17. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    International Nuclear Information System (INIS)

    Welch, Danny R; Steeg, Patricia S; Rinker-Schaeffer, Carrie W

    2000-01-01

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  18. Breast Cancer Metastasis to the Stomach That Was Diagnosed after Endoscopic Submucosal Dissection

    Directory of Open Access Journals (Sweden)

    Masahide Kita

    2016-01-01

    Full Text Available A 52-year-old woman presented with stage IIB primary breast cancer (cT2N1M0, which was treated using neoadjuvant chemotherapy (epirubicin, cyclophosphamide, and paclitaxel. However, the tumor persisted in patchy areas; therefore, we performed modified radical mastectomy and axillary lymph node dissection. Routine endoscopy at 8 months revealed a depressed lesion on the gastric angle’s greater curvature, and histology revealed signet ring cell proliferation. We performed endoscopic submucosal dissection for gastric cancer, although immunohistochemistry revealed that the tumor was positive for estrogen receptor, mammaglobin, and gross cystic disease fluid protein-15 (E-cadherin-negative. Therefore, we revised the diagnosis to gastric metastasis from the breast cancer.

  19. Computed tomography of the breast cancer

    International Nuclear Information System (INIS)

    Chung, Soo Young; Lee, Yul; Bae, Sang Hoon; Yoon, Jong Sup; Lee, Ki Chu

    1985-01-01

    The indication of computed tomography for the breast lesion are 1) Unusually extensive or small breast caused technical difficulties in performing mammograms. 2) Questionable mammographic findings, especially in dense proliferative breast parenchyme. 3) Microcancer. 4) Suspicious regional lymph node enlargement or invasive of the chest wall by breast cancer. The diagnosis of breast CT in breast cancer is based on pathologic anatomic changes and characteristic increase of mean CT No. of lesion following contrast enhancement. Authors analysed CT of the 34 patients who were clinically suspected breast cancer, and compared with mammography. The results are as follows: 1. Pathological diagnosis of 34 cases were 27 cases of breast cancer, 4 cases of fibrocystic disease, 2 cases of fibroadenoma, and 1 case of intraductal papilloma. The diagnostic accuracy of CT in 27 breast cancer was 93% (25 cases) and mammography 71% (19 case). 2. Correct diagnosis of CT in 7 benign breast disease is in 5 cases and mammography in 5 cases. 3. The most important finding of CT in breast cancer is characteristic increase of CT No. of lesion following contrast enhancement (200 ml, 65%): over average 50 HU in 19 cases of 27 breast cancers, 30-50 HU in a 6 cases, 20-30 HU in 2 cases with tumor necrosis. 4. Computed with mammography, other more valuable CT findings of breast cancer are axillary lymph node enlargement and adjacentic pectoral muscle invasion. 5. In conclusion, breast CT is considered as valuable diagnostic tool in evaluation of breast cancer, but not of benign breast disease

  20. Computed tomography of the breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Soo Young; Lee, Yul; Bae, Sang Hoon; Yoon, Jong Sup; Lee, Ki Chu [Hallym University Medical Center, Seoul (Korea, Republic of)

    1985-12-15

    The indication of computed tomography for the breast lesion are 1) Unusually extensive or small breast caused technical difficulties in performing mammograms. 2) Questionable mammographic findings, especially in dense proliferative breast parenchyme. 3) Microcancer. 4) Suspicious regional lymph node enlargement or invasive of the chest wall by breast cancer. The diagnosis of breast CT in breast cancer is based on pathologic anatomic changes and characteristic increase of mean CT No. of lesion following contrast enhancement. Authors analysed CT of the 34 patients who were clinically suspected breast cancer, and compared with mammography. The results are as follows: 1. Pathological diagnosis of 34 cases were 27 cases of breast cancer, 4 cases of fibrocystic disease, 2 cases of fibroadenoma, and 1 case of intraductal papilloma. The diagnostic accuracy of CT in 27 breast cancer was 93% (25 cases) and mammography 71% (19 case). 2. Correct diagnosis of CT in 7 benign breast disease is in 5 cases and mammography in 5 cases. 3. The most important finding of CT in breast cancer is characteristic increase of CT No. of lesion following contrast enhancement (200 ml, 65%): over average 50 HU in 19 cases of 27 breast cancers, 30-50 HU in a 6 cases, 20-30 HU in 2 cases with tumor necrosis. 4. Computed with mammography, other more valuable CT findings of breast cancer are axillary lymph node enlargement and adjacentic pectoral muscle invasion. 5. In conclusion, breast CT is considered as valuable diagnostic tool in evaluation of breast cancer, but not of benign breast disease.

  1. RANKL/RANK: from bone loss to the prevention of breast cancer.

    Science.gov (United States)

    Sigl, Verena; Jones, Laundette P; Penninger, Josef M

    2016-11-01

    RANK and RANKL, a receptor ligand pair belonging to the tumour necrosis factor family, are the critical regulators of osteoclast development and bone metabolism. Besides their essential function in bone, RANK and RANKL have also been identified as the key factors for the formation of a lactating mammary gland in pregnancy. Mechanistically, RANK and RANKL link the sex hormone progesterone with stem cell expansion and proliferation of mammary epithelial cells. Based on their normal physiology, RANKL/RANK control the onset of hormone-induced breast cancer through the expansion of mammary progenitor cells. Recently, we and others were able to show that RANK and RANKL are also critical regulators of BRCA1-mutation-driven breast cancer. Currently, the preventive strategy for BRCA1-mutation carriers includes preventive mastectomy, associated with wide-ranging risks and psychosocial effects. The search for an alternative non-invasive prevention strategy is therefore of paramount importance. As our work strongly implicates RANK and RANKL as key molecules involved in the initiation of BRCA1-associated breast cancer, we propose that anti-RANKL therapy could be a feasible preventive strategy for women carrying BRCA1 mutations, and by extension to other women with high risk of breast cancer. © 2016 The Authors.

  2. Male breast cancer

    DEFF Research Database (Denmark)

    Lautrup, Marianne D; Thorup, Signe S; Jensen, Vibeke

    2018-01-01

    OBJECTIVE: Describe prognostic parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980-2009. Determine all-cause mortality compared to the general male population and analyze survival/mortality compared with Danish female breast cancer patients (FBCP) in the same period...

  3. Unemployment among breast cancer survivors.

    Science.gov (United States)

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg; Badsberg, Jens Henrik; Osler, Merete

    2014-05-01

    Though about 20% of working age breast cancer survivors do not return to work after treatment, few studies have addressed risk factors for unemployment. The majority of studies on occupational consequences of breast cancer focus on non-employment, which is a mixture of sickness absence, unemployment, retirement pensions and other reasons for not working. Unemployment in combination with breast cancer may represent a particular challenge for these women. The aim of the present study is therefore to analyze the risk for unemployment in the years following diagnosis and treatment for breast cancer. This study included 14,750 women diagnosed with breast cancer in Denmark 2001-2009 identified through a population-based clinical database and linked with information from Danish administrative population based registers for information on labour market affiliation, socio-demography and co-morbid conditions. Multivariable analyses were performed by Cox's proportional hazard models. Two years after treatment, 81% of patients were still part of the work force, 10% of which were unemployed. Increasing duration of unemployment before breast cancer was associated with an adjusted HR = 4.37 (95% CI: 3.90-4.90) for unemployment after breast cancer. Other risk factors for unemployment included low socioeconomic status and demography, while adjuvant therapy did not increase the risk of unemployment. Duration of unemployment before breast cancer was the most important determinant of unemployment after breast cancer treatment. This allows identification of a particularly vulnerable group of patients in need of rehabilitation.

  4. Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Claire Jackson

    2013-01-01

    Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

  5. The 18-kDa translocator protein (TSPO disrupts mammary epithelial morphogenesis and promotes breast cancer cell migration.

    Directory of Open Access Journals (Sweden)

    Xiaoting Wu

    Full Text Available Mitochondria play important roles in cancer progression and have emerged as viable targets for cancer therapy. Increasing levels of the outer mitochondrial membrane protein, 18-kDa translocator protein (TSPO, are associated with advancing breast cancer stage. In particular, higher TSPO levels are found in estrogen receptor (ER-negative breast tumors, compared with ER-positive tumors. In this study, we sought to define the roles of TSPO in the acquisition of breast cancer malignancy. Using a three-dimensional Matrigel culture system, we determined the impact of elevated TSPO levels on mammary epithelial morphogenesis. Our studies demonstrate that stable overexpression of TSPO in mammary epithelial MCF10A acini drives proliferation and provides partial resistance to luminal apoptosis, resulting in enlarged acinar structures with partially filled lumen that resemble early stage breast lesions leading to breast cancer. In breast cancer cell lines, TSPO silencing or TSPO overexpression significantly altered the migratory activity. In addition, we found that combination treatment with the TSPO ligands (PK 11195 or Ro5-4864 and lonidamine, a clinical phase II drug targeting mitochondria, decreased viability of ER-negative breast cancer cell lines. Taken together, these data demonstrate that increases in TSPO levels at different stages of breast cancer progression results in the acquisition of distinct properties associated with malignancy. Furthermore, targeting TSPO, particularly in combination with other mitochondria-targeting agents, may prove useful for the treatment of ER-negative breast cancer.

  6. Breast Cancer Basics and You

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Breast Cancer Basics and You Past Issues / Summer 2014 Table ... more than 232,670 new cases of female breast cancer in the United States in 2014. More than ...

  7. Retrospective observation on contribution and limitations of screening for breast cancer with mammography in Korea: detection rate of breast cancer and incidence rate of interval cancer of the breast.

    Science.gov (United States)

    Lee, Kunsei; Kim, Hyeongsu; Lee, Jung Hyun; Jeong, Hyoseon; Shin, Soon Ae; Han, Taehwa; Seo, Young Lan; Yoo, Youngbum; Nam, Sang Eun; Park, Jong Heon; Park, Yoo Mi

    2016-11-18

    The purpose of this study was to determine the benefits and limitations of screening for breast cancer using mammography. Descriptive design with follow-up was used in the study. Data from breast cancer screening and health insurance claim data were used. The study population consisted of all participants in breast cancer screening from 2009 to 2014. Crude detection rate, positive predictive value and sensitivity and specificity of breast cancer screening and, incidence rate of interval cancer of the breast were calculated. The crude detection rate of breast cancer screening per 100,000 participants increased from 126.3 in 2009 to 182.1 in 2014. The positive predictive value of breast cancer screening per 100,000 positives increased from 741.2 in 2009 to 1,367.9 in 2014. The incidence rate of interval cancer of the breast per 100,000 negatives increased from 51.7 in 2009 to 76.3 in 2014. The sensitivities of screening for breast cancer were 74.6% in 2009 and 75.1% in 2014 and the specificities were 83.1% in 2009 and 85.7% in 2014. To increase the detection rate of breast cancer by breast cancer screening using mammography, the participation rate should be higher and an environment where accurate mammography and reading can be performed and reinforcement of quality control are required. To reduce the incidence rate of interval cancer of the breast, it will be necessary to educate women after their 20s to perform self-examination of the breast once a month regardless of participation in screening for breast cancer.

  8. Awareness of Breast Cancer and Breast Self Examination Among ...

    African Journals Online (AJOL)

    Background: Breast cancer is the commonest malignancy affecting women in Nigeria. Regular breast self examination reduces morbidity and mortality from this disease. Objective: To assess the knowledge of breast cancer, breast self examination and practice amongst secondary school teachers in Enugu , Nigeria.

  9. Early breast cancer

    International Nuclear Information System (INIS)

    Dongen, J.A. van

    1989-01-01

    The therapy of early breast cancer has been changing during the last decennium. It requires a multi-disciplinary approach and in each of these disciplines improvements have been implemented. The result is that treatment schedules can now be adapted to specific subgroups. In this review early breast cancer is defined as operable disease, using the criteria set out by Haagensen. Emphasis is given to describing the new developments in prognostic criteria, since these form the basis for creating subgroups for specific treatment schedules. Distinction is made between the factors relating to growth rate and those relating to metastatic potential. Data on screening promises a beneficial effect of the implementation of screening in national health care programs. Important shifts are seen in treatment schedules; the place of postoperative radiotherapy after classic ablative treatment is being challenged, whereas it plays a major role in the new breast conserving therapy schedules. The data mentioned in the review suggest that a large proportion of 'operable' cases can be treated with breast conservation but details in the technique of breast conserving therapy are still under investigation. They form a major part of the coming prospective studies in breast cancer. Improvements in reconstruction techniques, creating better cosmetic results, make reconstruction more competitive with breast conserving therapy. The use of chemotherapy and endocrine manipulation in early breast cancer has now been clearly confirmed by the overview technique by the Peto-group, thanks to all efforts of individual trialists together. (orig.)

  10. CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul

    2012-01-01

    PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer Assoc...

  11. Anticancer activity of litchi fruit pericarp extract against human breast cancer in vitro and in vivo

    International Nuclear Information System (INIS)

    Wang Xiujie; Yuan Shulan; Wang Jing; Lin Ping; Liu Guanjian; Lu Yanrong; Zhang Jie; Wang, Wendong; Wei Yuquan

    2006-01-01

    Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic compounds and exhibits powerful antioxidative activity against fat oxidation in vitro. The purpose of this study is to confirm the anticancer activity of LFP extract on human breast cancer in vitro and in vivo, and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation, and gene expression profiling after treatment with LFP extract. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for its anticancer activity and expression of caspase-3 in vivo by oral administration of 0.3% (0.3 mg/ml) of LFP water-soluble crude ethanolic extract (CEE) for 10 weeks. LFP extract demonstrated a dose- and time-dependent inhibitory effect on cell growth (IC 5 = 80 μg/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41(1.22%) up-regulated and 129 (3.84%) down-regulated genes after LFP water-soluble CEE treatment; the predominantly up-regulated genes were involved in various biological functions including cell cycle regulation and cell proliferation, apoptosis, signal transduction and transcriptional regulation, and extracellular matrix/adhesion molecules; and down-regulated genes were mainly associated with adhesion, invasion, and malignancy of cancer cells. A 40.70% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo experiment. The findings in this study suggested that LFP extract might have potential anticancer activity on both ER positive and negative breast cancers, which could be attributed, in part, to its DNA damage effect, proliferating inhibition and apoptosis induction of cancer cells through up-regulation and down-regulation of multiple genes involved in cell cycle regulation and cell

  12. CHL1 is involved in human breast tumorigenesis and progression

    Energy Technology Data Exchange (ETDEWEB)

    He, Li-Hong [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ma, Qin [Department of Oncology, The General Hospital of Tianjin Medical University, Tianjin (China); Shi, Ye-Hui [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie; Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Shu-Fen [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Tong, Zhong-Sheng, E-mail: 83352162@qq.com [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-08-23

    Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

  13. CHL1 is involved in human breast tumorigenesis and progression

    International Nuclear Information System (INIS)

    He, Li-Hong; Ma, Qin; Shi, Ye-Hui; Ge, Jie; Zhao, Hong-Meng; Li, Shu-Fen; Tong, Zhong-Sheng

    2013-01-01

    Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression

  14. DEGRO practical guidelines: radiotherapy of breast cancer II. Radiotherapy of non-invasive neoplasia of the breast

    International Nuclear Information System (INIS)

    Souchon, R.; Sautter-Bihl, M.L.; Sedlmayer, F.; Budach, W.; Dunst, J.; Feyer, P.; Fietkau, R.; Sauer, R.; Harms, W.; Wenz, F.; Haase, W.

    2014-01-01

    To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''non invasive breast cancer'', ''ductal carcinoma in situ, ''dcis'', ''borderline breast lesions'', ''lobular neoplasia'', ''radiotherapy'' and ''radiation therapy''. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly

  15. Cutaneous manifestations of breast cancer

    OpenAIRE

    Agnieszka B. Owczarczyk-Saczonek; Dawid Sigorski; Paweł Różanowski; Agnieszka Markiewicz; Waldemar J. Placek

    2017-01-01

    Breast cancer is the most common malignant neoplasm among women in Poland and in the European Union. According to most recent data of the Polish National Cancer Registry, in 2014 breast cancer was diagnosed in over 17,000 women. Based on the National Health Fund records, it is estimated that there are about 55,000–60,000 women in Poland who have a history of breast cancer diagnosis and are potentially at a risk of relapse. The most common sign of breast cancer is the presence of a nodule, how...

  16. Cell cycle regulatory proteins and miRNAs in premalignant lesions and breast cancer

    OpenAIRE

    Björner, Sofie

    2013-01-01

    Early diagnosis and reliable prognosis and treatment prediction of breast cancer will ultimately lead to a decreased mortality rate. This can be achieved by identification of prognostic and treatment predictive biomarkers, and by understanding the mechanisms behind early changes in the breast. The cell cycle is a closely controlled process, involving multiple components with regulation on several levels. Loss of adequate cell proliferation control and cell cycle regulation is one of the ma...

  17. Effect of specific silencing of EMMPRIN on the growth and cell cycle distribution of MCF-7 breast cancer cells.

    Science.gov (United States)

    Yang, X Q; Yang, J; Wang, R; Zhang, S; Tan, Q W; Lv, Q; Meng, W T; Mo, X M; Li, H J

    2015-12-02

    The extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a member of the immunoglobulin family and shows increased expression in tumor cells. We examined the effect of RNAi-mediated EMMPRIN gene silencing induced by lentiviral on the growth and cycle distribution of MCF-7 breast cancer cells. Lentiviral expressing EMMPRIN-short hairpin RNA were packaged to infect MCF-7 cells. The inhibition efficiency of EMMPRIN was validated by real-time fluorescent quantitation polymerase chain reaction and western blotting. The effect of EMMPRIN on cell proliferation ability was detected using the MTT assay and clone formation experiments. Changes in cell cycle were detected by flow cytometry. EMMPRIN-short hairpin RNA-packaged lentiviral significantly down-regulated EMMPRIN mRNA and protein expression, significantly inhibited cell proliferation and in vitro tumorigenicity, and induced cell cycle abnormalities. Cells in the G0/G1 and G2/M phases were increased, while cells in the S phase were decreased after infection of MCF-7 cells for 3 days. The EMMPRIN gene facilitates breast cancer cell malignant proliferation by regulating cell cycle distribution and may be a molecular target for breast cancer gene therapy.

  18. Expression of Metallothionein and Vascular Endothelial Growth Factor Isoforms in Breast Cancer Cells.

    Science.gov (United States)

    Wierzowiecka, Barbara; Gomulkiewicz, Agnieszka; Cwynar-Zajac, Lucja; Olbromski, Mateusz; Grzegrzolka, Jedrzej; Kobierzycki, Christopher; Podhorska-Okolow, Marzenna; Dziegiel, Piotr

    2016-01-01

    Metallothioneins (MTs) are low-molecular-weight and cysteine-rich proteins that bind heavy metal ions and oxygen-free radicals. MTs are commonly expressed in various tissues of mammals and are involved in regulation of cell proliferation and differentiation, and may be engaged in angiogenesis. Expression of MTs has been studied in many cancer types, especially breast cancer. The research results indicate that MTs may play important, although not yet fully known, roles in cancer angiogenesis. The aim of this study was to analyze the level of gene expression of selected MT isoforms induced with zinc ions in correlation with vascular endothelial growth factor (VEGF) isoforms in in vitro models of breast cancer. The studies were carried out in three breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231). An epithelial cell line derived from normal breast tissue (Me16c) was used as a control. The levels of expression of selected MT isoforms and selected genes involved in angiogenesis were studied with real-time PCR. Expression of different MT isoforms was induced by zinc ions to differing degrees in individual breast cancer cell lines. An increase in the expression of some MT isoforms was associated with a slight increase in the level of expression of VEGFA. The research results may indicate certain correlation between an increased expression of selected MT isoforms and a pro-angiogenic factor VEGF in specific types of breast cancer cells. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Histological evaluation of AMPK signalling in primary breast cancer

    International Nuclear Information System (INIS)

    Hadad, Sirwan M; Hardie, David G; Fleming, Stewart; Thompson, Alastair M; Baker, Lee; Quinlan, Philip R; Robertson, Katherine E; Bray, Susan E; Thomson, George; Kellock, David; Jordan, Lee B; Purdie, Colin A

    2009-01-01

    AMP-activated protein kinase (AMPK) acts as a cellular fuel gauge that responds to energy stress by suppressing cell growth and biosynthetic processes, thus ensuring that energy-consuming processes proceed only if there are sufficient metabolic resources. Malfunction of the AMPK pathway may allow cancer cells to undergo uncontrolled proliferation irrespective of their molecular energy levels. The aim of this study was to examine the state of AMPK phosphorylation histologically in primary breast cancer in relation to clinical and pathological parameters. Immunohistochemistry was performed using antibodies to phospho-AMPK (pAMPK), phospho-Acetyl Co-A Carboxylase (pACC) an established target for AMPK, HER2, ERα, and Ki67 on Tissue Micro-Array (TMA) slides of two cohorts of 117 and 237 primary breast cancers. The quick score method was used for scoring and patterns of protein expression were compared with clinical and pathological data, including a minimum 5 years follow up. Reduced signal, compared with the strong expression in normal breast epithelium, using a pAMPK antibody was demonstrated in 101/113 (89.4%) and 217/236 (91.9%) of two cohorts of patients. pACC was significantly associated with pAMPK expression (p = 0.007 & p = 0.014 respectively). For both cohorts, reduced pAMPK signal was significantly associated with higher histological grade (p = 0.010 & p = 0.021 respectively) and axillary node metastasis (p = 0.061 & p = 0.039 respectively). No significant association was found between pAMPK and any of HER2, ERα, or Ki67 expression, disease-free survival or overall survival. This study extends in vitro evidence through immunohistochemistry to confirm that AMPK is dysfunctional in primary breast cancer. Reduced signalling via the AMPK pathway, and the inverse relationship with histological grade and axillary node metastasis, suggests that AMPK re-activation could have therapeutic potential in breast cancer

  20. RECK is not an independent prognostic marker for breast cancer

    International Nuclear Information System (INIS)

    Gomes, Luciana R.; Fujita, André; Mott, Joni D.; Soares, Fernando A.; Labriola, Leticia; Sogayar, Mari C.

    2015-01-01

    The REversion-inducing Cysteine-rich protein with Kazal motif (RECK) is a well-known inhibitor of matrix metalloproteinases (MMPs) and cellular invasion. Although high expression levels of RECK have already been correlated with a better clinical outcome for several tumor types, its main function, as well as its potential prognostic value for breast cancer patients, remain unclear. The RECK expression profile was investigated in a panel of human breast cell lines with distinct aggressiveness potential. RECK functional analysis was undertaken using RNA interference methodology. RECK protein levels were also analyzed in 1040 cases of breast cancer using immunohistochemistry and tissue microarrays (TMAs). The association between RECK expression and different clinico-pathological parameters, as well as the overall (OS) and disease-free (DFS) survival rates, were evaluated. Higher RECK protein expression levels were detected in more aggressive breast cancer cell lines (T4-2, MDA-MB-231 and Hs578T) than in non-invasive (MCF-7 and T47D) and non-tumorigenic (S1) cell lines. Indeed, silencing RECK in MDA-MB-231 cells resulted in elevated levels of pro-MMP-9 and increased invasion compared with scrambled (control) cells, without any effect on cell proliferation. Surprisingly, by RECK immunoreactivity analysis on TMAs, we found no association between RECK positivity and survival (OS and DFS) in breast cancer patients. Even considering the different tumor subtypes (luminal A, luminal B, Her2 type and basal-like) or lymph node status, RECK remained ineffective for predicting the disease outcome. Moreover, by multivariate Cox regression analysis, we found that RECK has no prognostic impact for OS and DFS, relative to standard clinical variables. Although it continues to serve as an invasion and MMP inhibitor in breast cancer, RECK expression analysis is not useful for prognosis of these patients

  1. THE MAMMOGRAPHIC CALCIFICATIONS IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    Tang Ruiying; Liu Jingxian; Gaowen

    1998-01-01

    Objective: This study was performed to exam the relativeship between mammographic calcifications and breast cancer. Methods: All of the 184 patients with breast diseases underwent mammography before either an open biopsy or a mastectomy. The presence,morphology, and distribution of calcifications visualized on mammograms for breast cancer were compared with the controls who remained cancer free. Statistical comparisons were made by using the x2 test. Results:Of the 184 patients with breast diaeases, 93 malignant and 91 benign lesions were histologically confirmed.Calcifications were visualized on mammograms in 60(64%) of 93 breast cancers and 26 (28%) of 91 non breast cancers. The estimated odds ratio (OR) of breast cancer was 4.5 in women with calcifications seen on mammograms, compared with those having none (P<0.01). Of the 60 breast carcinomas having mammographic calcifications, 28 (47%) were infiltrating ductal carcinomas.There were only 8 (24%) cases with infiltrating ductal cancers in the group of without calcifications seen on the mammograms (P<0.05). Conclusion: Our finding suggests that mammographic calcification appears to be a risk factor for breast cancer. The granular and linear cast type calcification provide clues to the presence of breast cancer, especially when the carcinomas without associated masses were seen on mammograms.

  2. MicroRNA‑663b mediates TAM resistance in breast cancer by modulating TP73 expression.

    Science.gov (United States)

    Jiang, Hua; Cheng, Lin; Hu, Pan; Liu, Renbin

    2018-05-23

    Breast cancer is the second leading cause of cancer‑associated mortalities in women. Tamoxifen (TAM) is an endocrine therapy commonly used in the treatment of patients with breast cancer expressing estrogen receptor α. However, treatment often ends in failure due to the emergence of drug resistance. MicroRNAs (miRNAs), a family of small non‑coding RNAs, serve critical roles in the regulation of gene expression and cell events. To date, whether miRNA‑663b could mediate TAM resistance in breast cancer remains unknown. Therefore, the aim of the present study was to investigate the role of miRNA‑663b in TAM resistance in breast cancer. The results demonstrated that miRNA‑663b was upregulated in breast cancer with TAM resistance. Tumor protein 73 (TP73) was a direct target of miRNA‑663b, and was negatively regulated by miRNA‑663b in MCF‑7 cells. Furthermore, it was identified that downregulation of miRNA‑663b inhibited cell proliferation ability and promoted cell apoptosis, resulting in enhanced TAM sensitivity. In addition, these findings suggested that TP73 silencing may have eliminated the effects of miRNA‑663b inhibitor on breast cancer cells. In conclusion, the present study verified a novel molecular link between miRNA‑663b and TP73, and indicated that miRNA‑663b may be a critical therapeutic target in breast cancer.

  3. Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer.

    Science.gov (United States)

    Li, Xiu Juan; Ren, Zhao Jun; Tang, Jin Hai; Yu, Qiao

    2017-01-01

    Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics. © 2017 The Author(s). Published by S. Karger AG, Basel.

  4. Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Xiu Juan Li

    2017-12-01

    Full Text Available Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246 as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2, indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.

  5. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  6. Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms.

    Science.gov (United States)

    Sinha, Dona; Sarkar, Nivedita; Biswas, Jaydip; Bishayee, Anupam

    2016-10-01

    Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy against tumor cell proliferation, metastasis, epigenetic alterations and for induction of apoptosis as well as sensitization toward chemotherapeutic drugs in various in vitro and in vivo models of breast cancer. The roles of resveratrol as a phytoestrogen, an aromatase inhibitor and in stem cell therapy as well as adjuvent treatment are also discussed. This review explores the full potential of resveratrol in breast cancer prevention and treatment with current limitations, challenges and future directions of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Risk of treatment-related esophageal cancer among breast cancer survivors

    DEFF Research Database (Denmark)

    Morton, L M; Gilbert, E S; Hall, P

    2012-01-01

    Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use.......Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use....

  8. Tight correlation between expression of the Forkhead transcription factor FOXM1 and HER2 in human breast cancer

    Directory of Open Access Journals (Sweden)

    Hartmann Arndt

    2008-02-01

    Full Text Available Abstract Background FOXM1 regulates expression of cell cycle related genes that are essential for progression into DNA replication and mitosis. Consistent with its role in proliferation, elevated expression of FOXM1 has been reported in a variety of human tumour entities. FOXM1 is a gene of interest because recently chemical inhibitors of FOXM1 were described to limit proliferation and induce apoptosis in cancer cells in vitro, indicating that FOXM1 inhibitors could represent useful anticancer therapeutics. Methods Using immunohistochemistry (IHC we systematically analysed FOXM1 expression in human invasive breast carcinomas (n = 204 and normal breast tissues (n = 46 on a tissue microarray. Additionally, using semiquantitative realtime PCR, a collection of paraffin embedded normal (n = 12 and cancerous (n = 25 breast tissue specimens as well as benign (n = 3 and malignant mammary cell lines (n = 8 were investigated for FOXM1 expression. SPSS version 14.0 was used for statistical analysis. Results FOXM1 was found to be overexpressed in breast cancer in comparison to normal breast tissue both on the RNA and protein level (e.g. 8.7 fold as measured by realtime PCR. We found a significant correlation between FOXM1 expression and the HER2 status determined by HER2 immunohistochemistry (P P = 0.110. Conclusion FOXM1 may represent a novel breast tumour marker with prognostic significance that could be included into multi-marker panels for breast cancer. Interestingly, we found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently. Further studies are underway to analyse the potential interaction between FOXM1 and HER2, especially whether FOXM1 directly activates the HER2 promoter.

  9. Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer.

    Science.gov (United States)

    Xiong, Ting; Liu, Xiao-Wang; Huang, Xue-Long; Xu, Xiong-Feng; Xie, Wei-Quan; Zhang, Su-Jun; Tu, Jian

    2018-05-01

    Diallyl disulfide (DADS), a volatile component of garlic oil, has various biological properties, including antioxidant, antiangiogenic and anticancer effects. The present study aimed to explore novel targets of DADS that may slow or stop the progression of breast cancer. First, xenograft tumor models were created by subcutaneously injecting MCF-7 and MDA-MB-231 breast cancer cells into nude mice. Subsequently, western blot analysis was performed to investigate the expression of tristetraprolin (TTP), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in the xenograft tumors, and cell cultures. Tablet cloning, Transwell and wound healing assays revealed that DADS treatment significantly inhibited the proliferation, invasion and migration of breast cancer cells. In addition, DADS treatment led to significant downregulation of uPA and MMP-9 protein expression, but significantly upregulated TTP expression in vivo and in vitro . Knocking down TTP expression using small interfering RNA reversed the aforementioned effects of DADS, which suggests TTP is a key target of DADS in inhibiting the progression of breast cancer.

  10. Evidence that breast tissue stiffness is associated with risk of breast cancer.

    Science.gov (United States)

    Boyd, Norman F; Li, Qing; Melnichouk, Olga; Huszti, Ella; Martin, Lisa J; Gunasekara, Anoma; Mawdsley, Gord; Yaffe, Martin J; Minkin, Salomon

    2014-01-01

    Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer. Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements. An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement.

  11. Combining quantitative and qualitative breast density measures to assess breast cancer risk.

    Science.gov (United States)

    Kerlikowske, Karla; Ma, Lin; Scott, Christopher G; Mahmoudzadeh, Amir P; Jensen, Matthew R; Sprague, Brian L; Henderson, Louise M; Pankratz, V Shane; Cummings, Steven R; Miglioretti, Diana L; Vachon, Celine M; Shepherd, John A

    2017-08-22

    Accurately identifying women with dense breasts (Breast Imaging Reporting and Data System [BI-RADS] heterogeneously or extremely dense) who are at high breast cancer risk will facilitate discussions of supplemental imaging and primary prevention. We examined the independent contribution of dense breast volume and BI-RADS breast density to predict invasive breast cancer and whether dense breast volume combined with Breast Cancer Surveillance Consortium (BCSC) risk model factors (age, race/ethnicity, family history of breast cancer, history of breast biopsy, and BI-RADS breast density) improves identifying women with dense breasts at high breast cancer risk. We conducted a case-control study of 1720 women with invasive cancer and 3686 control subjects. We calculated ORs and 95% CIs for the effect of BI-RADS breast density and Volpara™ automated dense breast volume on invasive cancer risk, adjusting for other BCSC risk model factors plus body mass index (BMI), and we compared C-statistics between models. We calculated BCSC 5-year breast cancer risk, incorporating the adjusted ORs associated with dense breast volume. Compared with women with BI-RADS scattered fibroglandular densities and second-quartile dense breast volume, women with BI-RADS extremely dense breasts and third- or fourth-quartile dense breast volume (75% of women with extremely dense breasts) had high breast cancer risk (OR 2.87, 95% CI 1.84-4.47, and OR 2.56, 95% CI 1.87-3.52, respectively), whereas women with extremely dense breasts and first- or second-quartile dense breast volume were not at significantly increased breast cancer risk (OR 1.53, 95% CI 0.75-3.09, and OR 1.50, 95% CI 0.82-2.73, respectively). Adding continuous dense breast volume to a model with BCSC risk model factors and BMI increased discriminatory accuracy compared with a model with only BCSC risk model factors (C-statistic 0.639, 95% CI 0.623-0.654, vs. C-statistic 0.614, 95% CI 0.598-0.630, respectively; P breasts and fourth

  12. Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer

    Science.gov (United States)

    Yang, Li; Zha, Tian-Qi; He, Xiang; Chen, Liang; Zhu, Quan; Wu, Wei-Bing; Nie, Feng-Qi; Wang, Qian; Zang, Chong-Shuang; Zhang, Mei-Ling; He, Jing; Li, Wei; Jiang, Wen; Lu, Kai-Hua

    2018-01-01

    Pulmonary carcinoma-associated proteins have emerged as crucial players in governing fundamental biological processes such as cell proliferation, apoptosis and metastasis in human cancers. Placenta-specific protein 1 (PLAC1) is a cancer-related protein, which is activated and upregulated in a variety of malignant tissues, including prostate cancer, gastric adenocarcinoma, colorectal, epithelial ovarian and breast cancer. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression are still unknown. In the present study, we found that PLAC1 was significantly upregulated in NSCLC tissues, and its expression level was associated with advanced pathological stage and it was also correlated with shorter progression-free survival of lung cancer patients. Furthermore, knockdown of PLAC1 expression by siRNA inhibited cell proliferation, induced apoptosis and impaired invasive ability in NSCLC cells partly via regulation of epithelial-mesenchymal transition (EMT)-related protein expression. Our findings present that increased PLAC1 could be identified as a negative prognostic biomarker in NSCLC and regulate cell proliferation and invasion. Thus, we conclusively demonstrated that PLAC1 plays a key role in NSCLC development and progression, which may provide novel insights on the function of tumor-related gene-driven tumorigenesis. PMID:29138842

  13. DEGRO practical guidelines. Radiotherapy of breast cancer I. Radiotherapy following breast conserving therapy for invasive breast cancer

    International Nuclear Information System (INIS)

    Sedlmayer, F.

    2013-01-01

    Background and purpose: The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft fuer Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012. Methods: A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms 'breast cancer', 'radiotherapy', and 'breast conserving therapy'. Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer. Results: Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48-0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75-0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing research lies in partial breast

  14. Awareness of Breast Cancer and Practice of Breast Self ...

    African Journals Online (AJOL)

    Background and Objective: Breast cancer is the commonest cancer among women in globally and in Nigeria. In Nigeria, cases of breast cancer cases have been prevalent for three decades and more than 90% of cases can be detected by women themselves through breast self – examination. The objective of this study ...

  15. A cytotoxic Petiveria alliacea dry extract induces ATP depletion and decreases β-F1-ATPase expression in breast cancer cells and promotes survival in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    John F. Hernández

    Full Text Available Abstract Metabolic plasticity in cancer cells assures cell survival and cell proliferation under variable levels of oxygen and nutrients. Therefore, new anticancer treatments endeavor to target such plasticity by modifying main metabolic pathways as glycolysis or oxidative phosphorylation. In American traditional medicine Petiveria alliacea L., Phytolaccacea, leaf extracts have been used for leukemia and breast cancer treatments. Herein, we study cytotoxicity and antitumoral effects of P. alliacea extract in tumor/non-tumorigenic cell lines and murine breast cancer model. Breast cancer cells treated with P. alliacea dry extract showed reduction in β-F1-ATPase expression, glycolytic flux triggering diminished intracellular ATP levels, mitochondrial basal respiration and oxygen consumption. Consequently, a decline in cell proliferation was observed in conventional and three-dimension spheres breast cancer cells culture. Additionally, in vivo treatment of BALB/c mice transplanted with the murine breast cancer TS/A tumor showed that P. alliacea extract via i.p. decreases the primary tumor growth and increases survival in the TS/A model.

  16. A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Kawa, Seiji [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan); Matsushita, Hirohisa; Ohbayashi, Hirokazu [Department of Research and Development, Nichirei Biosciences Inc., Tokyo 104-8402 (Japan); Semba, Kentaro [Department of Life Science and Medical Bio-Science, School of Science and Engineering, Waseda University, Tokyo 169-8555 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan)

    2009-07-03

    Overexpression of ErbB2 in breast cancer is associated with increased recurrence and worse prognosis. Accumulating evidences suggest that molecular targeted therapy is a promising anticancer strategy. In this study, we produced a novel anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from the trastuzumab binding site. 6G10 induced aggregation of BT474 breast cancer cells and inhibited proliferation of various breast cancer cell lines including BT474. A growth inhibition assay showed that 6G10 had EC{sub 50} values comparable to trastuzumab, indicating that the drugs have a similar level of potency. Furthermore, intraperitoneal administration of 6G10 completely inhibited the growth of xenografted tumors derived from BT474 and SK-BR-3 cells. These data suggested that 6G10 has great therapeutic potential and could be administered to patients alternatively, or synergistically, with trastuzumab.

  17. Obesity and Breast Cancer.

    Science.gov (United States)

    Fortner, Renée T; Katzke, Verena; Kühn, Tilman; Kaaks, Rudolf

    The relationship between adiposity and breast cancer risk and prognosis is complex, with associations that differ depending on when body size is assessed (e.g., pre- vs. postmenopausal obesity) and when breast cancer is diagnosed (i.e., pre- vs. postmenopausal disease). Further, the impact of obesity on risk differs by tumor hormone receptor status (e.g., estrogen (ER) and progesterone (PR) receptor) and, among postmenopausal women, use of exogenous hormones (i.e., hormone replacement therapy (HRT)). In the context of these complexities, this review focuses on associations between childhood and adolescent adiposity, general adiposity, weight changes (i.e., loss and gain), abdominal adiposity, and breast cancer risk and survival. Finally, we discuss potential mechanisms linking adiposity to breast cancer.

  18. [Management of breast cancer in a woman with breast implants].

    Science.gov (United States)

    Remacle, S; Lifrange, E; Nizet, J-L

    2015-01-01

    The incidence of breast cancer, currently one woman on eight, also concerns patients who underwent augmentation surgery. Breast implants have already been the subject of numerous publications concerning the risk of inducing breast cancer or of delaying its diagnosis; however, no significant causal relationship has been established. The purpose of this article is to assess the diagnostic and therapeutic consequences when breast cancer is identified in a patient with breast implants.

  19. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass.

    Science.gov (United States)

    Spinelli, Jessica B; Yoon, Haejin; Ringel, Alison E; Jeanfavre, Sarah; Clish, Clary B; Haigis, Marcia C

    2017-11-17

    Ammonia is a ubiquitous by-product of cellular metabolism; however, the biological consequences of ammonia production are not fully understood, especially in cancer. We found that ammonia is not merely a toxic waste product but is recycled into central amino acid metabolism to maximize nitrogen utilization. In our experiments, human breast cancer cells primarily assimilated ammonia through reductive amination catalyzed by glutamate dehydrogenase (GDH); secondary reactions enabled other amino acids, such as proline and aspartate, to directly acquire this nitrogen. Metabolic recycling of ammonia accelerated proliferation of breast cancer. In mice, ammonia accumulated in the tumor microenvironment and was used directly to generate amino acids through GDH activity. These data show that ammonia is not only a secreted waste product but also a fundamental nitrogen source that can support tumor biomass. Copyright © 2017, American Association for the Advancement of Science.

  20. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    International Nuclear Information System (INIS)

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E.; Pai, Melody; Bayani, Nora; Blakely, Eleanor A.; Gray, Joe W.; Mao, Jian-Hua

    2010-01-01

    HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression were validated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels

  1. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  2. Levels of estrogen, carcinoembryonic antigen and cancer antigen of breast in breast cancer patients

    International Nuclear Information System (INIS)

    Abdelhadi, H. A.

    2005-09-01

    This study was conducted during the period from february 2004 to July 2004; with the objective of measuring the levels of estrogen (E2), carcinoembryonic antigen (CEA) and cancer antigen of breast (CA-15.3) so as to facilitate the early diagnosis of breast cancer and determine the involvement of these parameters as risk factors for breast cancer. Ninety blood samples were collected from Sudanese females, divided into two groups; control group and patient groups. The patients group was sixty Sudanese females visiting the Radio Isotope Center, Khartoum (RICK) and they were confirmed as breast cancer patient by histopathology. The levels of the above mentioned parameters were determined by using radioimmunoassay technique. The results showed that, no significant (p=0.05) difference between the levels of the estrogen in patients compared to the control, on the other hand there was non significant (p>0.05) elevation in CEA levels in the patients with breast cancer compared to the control. The level of CA15.3 was significantly (p<0.0001) higher in the breast cancer patients compared to the control.(Author)

  3. TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth.

    Science.gov (United States)

    Haricharan, Svasti; Brown, Powel

    2015-06-23

    Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

  4. Effect of acadesine on breast cancer cells under hypoxia

    Directory of Open Access Journals (Sweden)

    A. M. Shcherbakov

    2017-01-01

    Full Text Available The riboside derivative acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside is currently being tested in clinical trials as a promising anti-tumor drug. Intracellular target of acadesine is adenosine monophosphate-activated protein kinase (АМРК, an important regulatory molecule of energy metabolism. It is expected that acadesine would be active in tumors under hypoxia conditions. In normoxia (cells incubated in 21 % oxygen, acadesine inhibited proliferation and induced cell death of breast adenocarcinoma, including the triple negative breast cancer line. When oxygen partial pressure was decreased to 1 % (experimental hypoxia, acadesine inhibited activation of reporter construct responsive to HIF-1α (hypoxia inducible factor 1 alpha transcription factor. This effect was observed for acadesine in concentrations close to cytotoxic. Acadesine retained cytotoxicity under hypoxia and decreased the survival of the MDA-MB-231 cell line when used in combination with cisplatin. These results considerably widen acadesine’s field of application and allow to assume its efficacy in chemotherapy combination regimens for breast cancer, including the tumors with low oxygenation.

  5. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    Science.gov (United States)

    2016-06-20

    Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  6. Association between breast cancer, breast density, and body adiposity evaluated by MRI

    International Nuclear Information System (INIS)

    Zhu, Wenlian; Huang, Peng; Macura, Katarzyna J.; Artemov, Dmitri

    2016-01-01

    Despite the lack of reliable methods with which to measure breast density from 2D mammograms, numerous studies have demonstrated a positive association between breast cancer and breast density. The goal of this study was to study the association between breast cancer and body adiposity, as well as breast density quantitatively assessed from 3D MRI breast images. Breast density was calculated from 3D T1-weighted MRI images. The thickness of the upper abdominal adipose layer was used as a surrogate marker for body adiposity. We evaluated the correlation between breast density, age, body adiposity, and breast cancer. Breast density was calculated for 410 patients with unilateral invasive breast cancer, 73 patients with ductal carcinoma in situ (DCIS), and 361 controls without breast cancer. Breast density was inversely related to age and the thickness of the upper abdominal adipose layer. Breast cancer was only positively associated with body adiposity and age. Age and body adiposity are predictive of breast density. Breast cancer was not associated with breast density; however, it was associated with the thickness of the upper abdominal adipose layer, a surrogate marker for body adiposity. Our results based on a limited number of patients warrant further investigations. (orig.)

  7. IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3.

    Directory of Open Access Journals (Sweden)

    Alpa V Patel

    2008-07-01

    Full Text Available IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3. This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.

  8. Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xiulong, E-mail: songxiulong@hotmail.com; Wei, Zhengxi; Shaikh, Zahir A., E-mail: zshaikh@uri.edu

    2015-08-15

    Cadmium (Cd) is a common environmental toxicant and an established carcinogen. Epidemiological studies implicate Cd with human breast cancer. Low micromolar concentrations of Cd promote proliferation of human breast cancer cells in vitro. The growth promotion of breast cancer cells is associated with the activation of MAPK/ERK pathway. This study explores the mechanism of Cd-induced activation of MAPK/ERK pathway. Specifically, the role of cell surface receptors ERα, EGFR, and Src kinase was evaluated in human breast cancer MCF-7 cells treated with 1–3 μM Cd. The activation of ERK was studied using a serum response element (SRE) luciferase reporter assay. Receptor phosphorylation was detected by Western blot analyses. Cd treatment increased both the SRE reporter activity and ERK1/2 phosphorylation in a concentration-dependent manner. Cd treatment had no effect on reactive oxygen species (ROS) generation. Also, blocking the entry of Cd into the cells with manganese did not diminish Cd-induced activation of MAPK/ERK. These results suggest that the effect of Cd was likely not caused by intracellular ROS generation, but through interaction with the membrane receptors. While Cd did not appear to activate either EGFR or Src kinase, their inhibition completely blocked the Cd-induced activation of ERK as well as cell proliferation. Similarly, silencing ERα with siRNA or use of ERα antagonist blocked the effects of Cd. Based on these results, it is concluded that not only ERα, but also basal activities of EGFR and Src kinase are essential for Cd-induced signal transduction and activation of MAPK/ERK pathway for breast cancer cell proliferation. - Highlights: • Low micromolar concentrations of Cd rapidly activate ERK1/2 in MCF-7 cells. • Signal transduction and resulting cell proliferation require EGFR, ERα, and Src. • These findings implicate Cd in promotion of breast cancer.

  9. Getting free of breast cancer

    DEFF Research Database (Denmark)

    Halttunen, Arja; Hietanen, P; Jallinoja, P

    1992-01-01

    Twenty-two breast cancer patients who were relapse-free and had no need for cancer-related treatment were interviewed 8 years after mastectomy in order to evaluate their feelings of getting free of breast cancer and the meaning of breast cancer in their lives. The study is a part of an intervention...... and follow-up study of 57 breast cancer patients. Half of the 22 patients still had frequent or occasional thoughts of recurrence and over two-thirds still thought they had not been 'cured' of cancer. More than half of the patients admitted that going through breast cancer had made them more mature. Women...... who had less thoughts of recurrence belonged to a group that had gone through an eight-week group psychotherapy intervention, were less depressed and had more other illnesses. Women who felt 'cured' had less limitations and restrictions due to cancer and belonged more often to higher social classes...

  10. Identification of cell proliferation, immune response and cell migration as critical pathways in a prognostic signature for HER2+:ERα- breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Liu

    Full Text Available Multi-gene prognostic signatures derived from primary tumor biopsies can guide clinicians in designing an appropriate course of treatment. Identifying genes and pathways most essential to a signature performance may facilitate clinical application, provide insights into cancer progression, and uncover potentially new therapeutic targets. We previously developed a 17-gene prognostic signature (HTICS for HER2+:ERα- breast cancer patients, using genes that are differentially expressed in tumor initiating cells (TICs versus non-TICs from MMTV-Her2/neu mammary tumors. Here we probed the pathways and genes that underlie the prognostic power of HTICS.We used Leave-One Out, Data Combination Test, Gene Set Enrichment Analysis (GSEA, Correlation and Substitution analyses together with Receiver Operating Characteristic (ROC and Kaplan-Meier survival analysis to identify critical biological pathways within HTICS. Publically available cohorts with gene expression and clinical outcome were used to assess prognosis. NanoString technology was used to detect gene expression in formalin-fixed paraffin embedded (FFPE tissues.We show that three major biological pathways: cell proliferation, immune response, and cell migration, drive the prognostic power of HTICS, which is further tuned by Homeostatic and Glycan metabolic signalling. A 6-gene minimal Core that retained a significant prognostic power, albeit less than HTICS, also comprised the proliferation/immune/migration pathways. Finally, we developed NanoString probes that could detect expression of HTICS genes and their substitutions in FFPE samples.Our results demonstrate that the prognostic power of a signature is driven by the biological processes it monitors, identify cell proliferation, immune response and cell migration as critical pathways for HER2+:ERα- cancer progression, and defines substitutes and Core genes that should facilitate clinical application of HTICS.

  11. Micropapillary Lung Cancer with Breast Metastasis Simulating Primary Breast Cancer due to Architectural Distortion on Images

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kyung Ran; Hong, Eun Kyung; Lee, See Yeon [Center for Breast Cancer, National Cancer Center, Goyang (Korea, Republic of); Ro, Jae Yoon [The Methodist Hospital, Weill Medical College of Cornell University, Houston (United States)

    2012-03-15

    A 47-year-old Korean woman with right middle lobe lung adenocarcinoma, malignant pleural effusion, and multiple lymph node and bone metastases, after three months of lung cancer diagnosis, presented with a palpable right breast mass. Images of the right breast demonstrated architectural distortion that strongly suggested primary breast cancer. Breast biopsy revealed metastatic lung cancer with a negative result for estrogen receptor (ER), progesterone receptor (PR) and mammaglobin, and a positive result for thyroid transcription factor-1 (TTF-1). We present a case of breast metastasis from a case of lung cancer with an extensive micropapillary component, which was initially misinterpreted as a primary breast cancer due to unusual image findings with architectural distortion.

  12. Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

    International Nuclear Information System (INIS)

    Mannello, Ferdinando; Ligi, Daniela

    2013-01-01

    One of the major goals in cancer research is to find and evaluate the early presence of biomarkers in human fluids and tissues. To resolve the complex cell heterogeneity of a tumor mass, it will be useful to characterize the intricate biomolecular composition of tumor microenvironment (the so called cancer secretome), validating secreted proteins as early biomarkers of cancer initiation and progression. This approach is not broadly applicable because of the paucity of well validated and FDA-approved biomarkers and because most of the candidate biomarkers are mainly organ-specific rather than tumor-specific. For these reasons, there is an urgent need to identify and validate a panel of biomarker combinations for early detection of human tumors. This is especially important for breast cancer, the cancer spread most worldwide among women. It is well known that patients with early diagnosed breast cancer live longer, require less extensive treatment and fare better than patients with more aggressive and/or advanced disease. In the frame of searching breast cancer biomarkers (especially using nipple aspirate fluid mirroring breast microenvironment), studies have highlighted an optimal combination of well-known biomarkers: uPA + PAI-1 + TF. When individually investigated they did not show perfect accuracy in predicting the presence of breast cancer, whereas the triple combination has been demonstrated to be highly predictive of pre-cancer and/or cancerous conditions, approaching 97-100% accuracy. Despite the heterogeneous composition of breast cancer and the difficulties to find specific breast cancer biomolecules, the noninvasive analysis of the nipple aspirate fluid secretome may significantly improve the discovery of promising biomarkers, helping also the differentiation among benign and invasive breast diseases, opening new frontiers in early oncoproteomics

  13. Lysine methyltransferase SMYD2 promotes triple negative breast cancer progression.

    Science.gov (United States)

    Li, Linda Xiaoyan; Zhou, Julie Xia; Calvet, James P; Godwin, Andrew K; Jensen, Roy A; Li, Xiaogang

    2018-02-27

    We identified SMYD2, a SMYD (SET and MYND domain) family protein with lysine methyltransferase activity, as a novel breast cancer oncogene. SMYD2 was expressed at significantly higher levels in breast cancer cell lines and in breast tumor tissues. Silencing of SMYD2 by RNAi in triple-negative breast cancer (TNBC) cell lines or inhibition of SMYD2 with its specific inhibitor, AZ505, significantly reduced tumor growth in vivo. SMYD2 executes this activity via methylation and activation of its novel non-histone substrates, including STAT3 and the p65 subunit of NF-κB, leading to increased TNBC cell proliferation and survival. There are cross-talk and synergistic effects among SMYD2, STAT3, and NF-κB in TNBC cells, in that STAT3 can contribute to the modification of NF-κB p65 subunit post-translationally by recruitment of SMYD2, whereas the p65 subunit of NF-κB can also contribute to the modification of STAT3 post-translationally by recruitment of SMYD2, leading to methylation and activation of STAT3 and p65 in these cells. The expression of SMYD2 can be upregulated by IL-6-STAT3 and TNFα-NF-κB signaling, which integrates epigenetic regulation to inflammation in TNBC development. In addition, we have identified a novel SMYD2 transcriptional target gene, PTPN13, which links SMYD2 to other known breast cancer associated signaling pathways, including ERK, mTOR, and Akt signaling via PTPN13 mediated phosphorylation.

  14. LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145.

    Science.gov (United States)

    Lei, Hongwei; Gao, Yan; Xu, Xiaoying

    2017-07-01

    LncRNA TUG1, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, its biological function in thyroid cancer cells has not been elucidated. The aim of this study is to measure TUG1 expression level and evaluate its function in thyroid cancer cells. LncRNA TUG1 expression levels in thyroid cancer tissues and three thyroid cancer cell lines (the ATC cell lines SW1736 and KAT18 and the FTC cell line FTC133) were assessed by qRT-PCR and compared with that of the human normal breast epithelial cell HGC-27. MTT assay, colony formation assay, transwell assay and western blot analysis were performed to assess the effects of TUG1 on proliferation, metastasis and EMT formation in thyroid cancer cells in vitro. Rescue assay was performed to further confirm that TUG1 contributes to the progression of thyroid cancer cells through regulating miR-145/ZEB1 signal pathway. LncRNA TUG1 was found to be up-regulated in thyroid cancer tissues and thyroid cancer cells compared with that in the human normal breast epithelial cell HGC-27. Increased lncRNA TUG1 expression was found to significantly promote tumor cell proliferation, and facilitate cell invasion, while down-regulated TUG1 could obviously inhibit cell proliferation, migration/invasion and reverse EMT to MET. These results indicated that TUG1 may contribute to the progression of thyroid cancer cells by function as a ceRNA competitive sponging miR-145, and that lncRNA TUG1 is associated with tumor progression in thyroid cancer cells. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Lentiviral Vector Mediated Claudin1 Silencing Inhibits Epithelial to Mesenchymal Transition in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xianqi Zhao

    2015-06-01

    Full Text Available Breast cancer has a high incidence and mortality rate worldwide. Several viral vectors including lentiviral, adenoviral and adeno-associated viral vectors have been used in gene therapy for various forms of human cancer, and have shown promising effects in controlling tumor development. Claudin1 (CLDN1 is a member of the tetraspan transmembrane protein family that plays a major role in tight junctions and is associated with tumor metastasis. However, the role of CLDN1 in breast cancer is largely unexplored. In this study, we tested the therapeutic potential of silencing CLDN1 expression in two breast cancer (MDA-MB-231 and MCF7 cell lines using lentiviral vector mediated RNA interference. We found that a CLDN1 short hairpin (shRNA construct efficiently silenced CLDN1 expression in both breast cancer cell lines, and CLDN1 knockdown resulted in reduced cell proliferation, survival, migration and invasion. Furthermore, silencing CLDN1 inhibited epithelial to mesenchymal transition (EMT by upregulating the epithelial cell marker, E-cadherin, and downregulating mesenchymal markers, smooth muscle cell alpha-actin (SMA and Snai2. Our data demonstrated that lentiviral vector mediated CLDN1 RNA interference has great potential in breast cancer gene therapy by inhibiting EMT and controlling tumor cell growth.

  16. RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.

    Science.gov (United States)

    Nolan, Emma; Vaillant, François; Branstetter, Daniel; Pal, Bhupinder; Giner, Göknur; Whitehead, Lachlan; Lok, Sheau W; Mann, Gregory B; Rohrbach, Kathy; Huang, Li-Ya; Soriano, Rosalia; Smyth, Gordon K; Dougall, William C; Visvader, Jane E; Lindeman, Geoffrey J

    2016-08-01

    Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers. We identified two subsets of luminal progenitors (RANK(+) and RANK(-)) in histologically normal tissue of BRCA1-mutation carriers and showed that RANK(+) cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. These data suggest that RANK(+) and not RANK(-) progenitors are a key target population in these women. Inhibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived from pre-neoplastic BRCA1(mut/+) tissue attenuated progesterone-induced proliferation. Notably, proliferation was markedly reduced in breast biopsies from BRCA1-mutation carriers who were treated with denosumab. Furthermore, inhibition of RANKL in a Brca1-deficient mouse model substantially curtailed mammary tumorigenesis. Taken together, these findings identify a targetable pathway in a putative cell-of-origin population in BRCA1-mutation carriers and implicate RANKL blockade as a promising strategy in the prevention of breast cancer.

  17. Racial and Socioeconomic Disparities Are More Pronounced in Inflammatory Breast Cancer Than Other Breast Cancers

    Directory of Open Access Journals (Sweden)

    Ryan A. Denu

    2017-01-01

    Full Text Available Inflammatory breast cancer (IBC is a rare yet aggressive form of breast cancer. We examined differences in patient demographics and outcomes in IBC compared to locally advanced breast cancer (LABC and all other breast cancer patients from the Breast and Prostate Cancer Data Quality and Patterns of Care Study (POC-BP, containing information from cancer registries in seven states. Out of 7,624 cases of invasive carcinoma, IBC and LABC accounted for 2.2% (N=170 and 4.9% (N=375, respectively. IBC patients were more likely to have a higher number (P=0.03 and severity (P=0.01 of comorbidities than other breast cancer patients. Among IBC patients, a higher percentage of patients with metastatic disease versus nonmetastatic disease were black, on Medicaid, and from areas of higher poverty and more urban areas. Black and Hispanic IBC patients had worse overall and breast cancer-specific survival than white patients; moreover, IBC patients with Medicaid, patients from urban areas, and patients from areas of higher poverty and lower education had worse outcomes. These data highlight the effects of disparities in race and socioeconomic status on the incidence of IBC as well as IBC outcomes. Further work is needed to reveal the causes behind these disparities and methods to improve IBC outcomes.

  18. Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals.

    Science.gov (United States)

    Klein, Andreas; Guhl, Eva; Zollinger, Raphael; Tzeng, Yin-Jeh; Wessel, Ralf; Hummel, Michael; Graessmann, Monika; Graessmann, Adolf

    2005-05-01

    Microarray studies revealed that as a first hit the SV40 T/t antigen causes deregulation of 462 genes in mammary gland cells (ME cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell proliferation specific and Rb-E2F dependent, causing ME cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal ME cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal ME cells. The profile of retransformants shows that only 38 deregulated genes are tumor-specific, and that none of them is considered to be a typical breast cancer gene.

  19. Mass spectrometric detection of 27-hydroxycholesterol in breast cancer exosomes.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Lund, Kaja; Seterdal, Kristina Erikstad; Solheim, Stian; Vehus, Tore; Solberg, Nina; Krauss, Stefan; Lundanes, Elsa; Wilson, Steven Ray

    2017-05-01

    Exosomes from cancer cells are rich sources of biomarkers and may contain elevated levels of lipids of diagnostic value. 27-Hydroxycholesterol (27-OHC) is associated with proliferation and metastasis in estrogen receptor positive (ER+) breast cancer. In this study, we investigated the levels of 27-OHC, and other sidechain-hydroxylated oxysterols in exosomes. To study both cytoplasmic and exosomal oxysterol samples of limited size, we have developed a capillary liquid chromatography-mass spectrometry platform that outperforms our previously published systems regarding chromatographic resolution, analysis time and sensitivity. In the analyzed samples, the quantified level of cytoplasmic 27-OHC using this platform fitted with mRNA levels of 27-OHC's corresponding enzyme, CYP27A1. We find clearly increased levels of 27-OHC in exosomes (i.e., enrichment) from an ER+ breast cancer cell line (MCF-7) compared to exosomes derived from an estrogen receptor (ER-) breast cancer cell line (MDA-MB-231) and other control exosomes (non-cancerous cell line (HEK293) and human pooled serum). The exosomal oxysterol profile did not reflect cytoplasmic oxysterol profiles in the cells of origin; cytoplasmic 27-OHC was low in ER+ MCF-7 cells while high in MDA-MB-231 cells. Other control cancer cells showed varied cytoplasmic oxysterol levels. Hence, exosome profiling in cancer cells might provide complementary information with the possibility of diagnostic value. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The potential role of Brachyury in inducing epithelial-to-mesenchymal transition (EMT) and HIF-1α expression in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Chao [Department of Mammary Surgery, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403 (China); Zhang, Jingjing, E-mail: jingjingzhangzs@163.com [Department of Cancer Radiotherapy, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403 (China); Fu, Jianhua [Department of Thoracic Surgery, Cancer Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403 (China); Ling, Feihai, E-mail: feihailingfhl@163.com [Department of Mammary Surgery, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403 (China)

    2015-11-27

    One of transcription factors of the T-box family, Brachyury has been implicated in tumorigenesis of many types of cancers, regulating cancer cell proliferation, metastasis, invasion and epithelial-to-mesenchymal transition (EMT). However, the role of Brachyury in breast cancer cells has been scarcely reported. The present study aimed to investigate the expression and role of Brachyury in breast cancer. Brachyury expression was analyzed by qRT-PCR and Western blot. The correlations between Brachyury expression and clinicopathological factors of breast cancer were determined. Involvement of EMT stimulation and hypoxia-inducible factor-1α (HIF-1α) expression induction by Brachyury was also evaluated. Moreover, the effect of Brachyury on tumor growth and metastasis in vivo was examined in a breast tumor xenograft model. Brachyury expression was enhanced in primary breast cancer tissues and Brachyury expression was correlated with tumor stage and lymph node metastasis. Hypoxia enhanced Brachyury expression, the silencing of which blocked the modulation effect of hypoxia on E-cadherin and vimentin expression. Brachyury significantly augmented HIF-1alpha expression via PTEN/Akt signaling as well as accelerated cell proliferation and migration in vitro. Additionally, Brachyury accelerated breast tumor xenograft growth and increased lung metastasis in nude mice. In summary, our data confirmed that Brachyury might contribute to hypoxia-induced EMT of breast cancer and trigger HIF-1alpha expression via PTEN/Akt signaling. - Highlights: • Brachyury expression was correlated with tumor stage and lymph node metastasis. • Hypoxia enhanced Brachyury expression, which contributes to hypoxia-induced EMT. • Brachyury significantly augmented HIF-1alpha expression via PTEN/Akt signaling. • Brachyury accelerated tumor xenograft growth and increased lung metastasis.

  1. Understanding and potentially reducing second breast cancer

    International Nuclear Information System (INIS)

    Brenner, D.

    2011-01-01

    Full text: Long term survival after breast cancer diagnosis has increased markedly in the last decade: 15-year relative survival after breast cancer diagnosis is now 75% in the US. Associated with these excellent survival prospects, however, long term studies suggest that contralateral second breast cancer rates are in the range from 10 to 15% at 15 years post treatment, and are still higher for BRCA1/2 carriers, as well as for still longer term survivors. These second cancer risks are much higher than those for a comparable healthy woman to develop a first breast cancer. It follows that women with breast cancer are highly prone to develop a second breast cancer. We propose here a new option for reducing the disturbingly high risk of a contralateral second breast cancer. in patients with both estrogen positive and negative primary breast cancer: prophylactic mammary irradiation (PMI) of the contralateral breast. The rationale behind PMI is evidence that standard post-Iumpectomy radiotherapy of the affected (ipsilateral) breast substantially reduces the long-term genetically-based second cancer risk in the ipsilateral breast, by killing the existing premalignant cells in that breast. This suggests that there are relatively few premalignant cells in the breast (hundreds or thousands, not millions), so even a fairly modest radiation cell-kill level across the whole breast would be expected to kill essentially all of them. If this is so, then a modest radiation dose-much lower than that to the affected breast--delivered uniformly to the whole contralateral breast, and typically delivered at the same time as the radiotherapy of the ipsilateral breast, would have the potential to markedly reduce second-cancer risks in the contralateral breast by killing essentially all the pre-malignant cells in that breast while causing only a very low level of radiation-induced sequelae. Therefore we hypothesize that low-dose prophylactic mammary irradiation of the contralateral breast

  2. Electrospinning PCL Scaffolds Manufacture for Three-Dimensional Breast Cancer Cell Culture

    Directory of Open Access Journals (Sweden)

    Marc Rabionet

    2017-08-01

    Full Text Available In vitro cell culture is traditionally performed within two-dimensional (2D environments, providing a quick and cheap way to study cell properties in a laboratory. However, 2D systems differ from the in vivo environment and may not mimic the physiological cell behavior realistically. For instance, 2D culture models are thought to induce cancer stem cells (CSCs differentiation, a rare cancer cell subpopulation responsible for tumor initiation and relapse. This fact hinders the development of therapeutic strategies for tumors with a high relapse percentage, such as triple negative breast cancer (TNBC. Thus, three-dimensional (3D scaffolds have emerged as an attractive alternative to monolayer culture, simulating the extracellular matrix structure and maintaining the differentiation state of cells. In this work, scaffolds were fabricated through electrospinning different poly(ε-caprolactone-acetone solutions. Poly(ε-caprolactone (PCL meshes were seeded with triple negative breast cancer (TNBC cells and 15% PCL scaffolds displayed significantly (p < 0.05 higher cell proliferation and elongation than the other culture systems. Moreover, cells cultured on PCL scaffolds exhibited higher mammosphere forming capacity and aldehyde dehydrogenase activity than 2D-cultured cells, indicating a breast CSCs enrichment. These results prove the powerful capability of electrospinning technology in terms of poly(ε-caprolactone nanofibers fabrication. In addition, this study has demonstrated that electrospun 15% PCL scaffolds are suitable tools to culture breast cancer cells in a more physiological way and to expand the niche of breast CSCs. In conclusion, three-dimensional cell culture using PCL scaffolds could be useful to study cancer stem cell behavior and may also trigger the development of new specific targets against such malignant subpopulation.

  3. Three-layered polyplex as a microRNA targeted delivery system for breast cancer gene therapy

    Science.gov (United States)

    Li, Yan; Dai, Yu; Zhang, Xiaojin; Chen, Jihua

    2017-07-01

    MicroRNAs (miRNAs), small non-coding RNAs, play an important role in modulating cell proliferation, migration, and differentiation. Since miRNAs can regulate multiple cancer-related genes simultaneously, regulating miRNAs could target a set of related oncogenic genes or pathways. Owing to their reduced immune response and low toxicity, miRNAs with small size and low molecular weight have become increasingly promising therapeutic drugs in cancer therapy. However, one of the major challenges of miRNAs-based cancer therapy is to achieve specific, effective, and safe delivery of therapeutic miRNAs into cancer cells. Here we provide a strategy using three-layered polyplex with folic acid as a targeting group to systemically deliver miR-210 into breast cancer cells, which results in breast cancer growth being inhibited.

  4. Extracts of strawberry fruits induce intrinsic pathway of apoptosis in breast cancer cells and inhibits tumor progression in mice.

    Directory of Open Access Journals (Sweden)

    Ranganatha R Somasagara

    Full Text Available The consumption of berry fruits, including strawberries, has been suggested to have beneficial effects against oxidative stress mediated diseases. Berries contain multiple phenolic compounds and secondary metabolites that contribute to their biological properties.Current study investigates the anticancer activity of the methanolic extract of strawberry (MESB fruits in leukaemia (CEM and breast cancer (T47D cell lines ex vivo, and its cancer therapeutic and chemopreventive potential in mice models. Results of MTT, trypan blue and LDH assays suggested that MESB can induce cytotoxicity in cancer cells, irrespective of origin, in a concentration- and time-dependent manner. Treatment of mice bearing breast adenocarcinoma with MESB blocked the proliferation of tumor cells in a time-dependent manner and resulted in extended life span. Histological and immunohistochemical studies suggest that MESB treatment affected tumor cell proliferation by activating apoptosis and did not result in any side effects. Finally, we show that MESB can induce intrinsic pathway of apoptosis by activating p73 in breast cancer cells, when tumor suppressor gene p53 is mutated.The present study reveals that strawberry fruits possess both cancer preventive and therapeutic values and we discuss the mechanism by which it is achieved.

  5. PET scan for breast cancer

    Science.gov (United States)

    ... radioactive substance (called a tracer) to look for breast cancer. This tracer can help identify areas of cancer ... only after a woman has been diagnosed with breast cancer. It is done to see if the cancer ...

  6. Breast cancer and breast health awareness as an evolving health promotion concept

    International Nuclear Information System (INIS)

    Plesnicar, A.; Kralj, B.; Kovac, V.

    2004-01-01

    Background. Breast cancer is the most frequent malignant disease in the majority of developed countries. In the last few years the introduction of mammography screening programmes has resulted in an improved survival of breast cancer patients. However, the incidence of the disease in these countries is still on the increase. Present focus on secondary breast cancer prevention activities, consisting of early detection and treatment, cannot ensure a decrease of breast cancer incidence. Improved breast health awareness could therefore represent a part of specific health promotion activities aimed at decreasing the incidence of breast cancer. Conclusions. In developed countries breast cancer is a significant health care issue. Secondary breast cancer prevention activities should therefore be complemented by specific health promotion activities in order to reduce its incidence in the future. Primary breast cancer prevention would include health promotion activities aimed at enhancement of the individual as well as collective breast health awareness. Properly enlightened members of the influential population groups could attain appropriate changes in the fields of legislation, taxation, customs and commercial regulations that would enable women to control their own breast health. (author)

  7. Immunophenotyping of hereditary breast cancer

    NARCIS (Netherlands)

    van der Groep, P.

    2009-01-01

    Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may

  8. Radiofrequency Tagged Surgery in Treating Patients With Breast Cancer

    Science.gov (United States)

    2018-06-18

    Positive Axillary Lymph Node; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

  9. Management of fertility preservation in young breast cancer patients in a large breast cancer centre.

    Science.gov (United States)

    Lawrenz, B; Neunhoeffer, E; Henes, M; Lessmann-Bechle, S; Krämer, B; Fehm, Tanja

    2010-11-01

    The increase of breast cancer in young women under 40 years and the increasing age of women at the time of the birth of their first child underlines the importance to implement counselling for fertility-preserving strategies in the management of breast cancer care. We present the fertility-preserving procedures performed after routine counselling for primary breast cancer patients in a large certified breast cancer centre. Since November 2006, patients aged below 40 years with histologically confirmed breast cancer are routinely counselled on fertility-preserving possibilities before breast surgery and chemotherapy in the fertility centre of the University Women's Hospital in Tuebingen. The recommendations are based on the treatment recommendations of the network FertiPROTEKT. During the last 40 months, 56 primary breast cancer patients were counselled. Forty-one of these patients were hormone receptor positive. Thirty-four patients (63%) underwent fertility-preserving strategies. The majority of the patients (n = 22) decided on ovarian tissue cryopreservation. GnRH protection was performed in 14 patients. In 12 patients an ovarian stimulation protocol was initiated to cryopreserve fertilized or unfertilized oocytes. A combination of different fertility-preserving methods was performed in 12 patients. The preservation of ovarian function and fertility are of great importance to young breast cancer patients. Counselling on fertility-preserving strategies is therefore critical in these patients and should be routinely performed.

  10. Statins and breast cancer prognosis

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Lash, Timothy L; Damkier, Per

    2014-01-01

    Much preclinical and epidemiological evidence supports the anticancer effects of statins. Epidemiological evidence does not suggest an association between statin use and reduced incidence of breast cancer, but does support a protective effect of statins-especially simvastatin-on breast cancer...... recurrence. Here, we argue that the existing evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins and we advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence......, then the indications for a safe, well tolerated, and inexpensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several trial design opportunities-including candidate predictive biomarkers of statin safety and efficacy-and off er solutions to the key challenges involved...

  11. Decline in breast cancer mortality

    DEFF Research Database (Denmark)

    Njor, Sisse Helle; Schwartz, Walter; Blichert-Toft, Mogens

    2015-01-01

    OBJECTIVES: When estimating the decline in breast cancer mortality attributable to screening, the challenge is to provide valid comparison groups and to distinguish the screening effect from other effects. In Funen, Denmark, multidisciplinary breast cancer management teams started before screening...... was introduced; both activities came later in the rest of Denmark. Because Denmark had national protocols for breast cancer treatment, but hardly any opportunistic screening, Funen formed a "natural experiment", providing valid comparison groups and enabling the separation of the effect of screening from other...... factors. METHODS: Using Poisson regression we compared the observed breast cancer mortality rate in Funen after implementation of screening with the expected rate without screening. The latter was estimated from breast cancer mortality in the rest of Denmark controlled for historical differences between...

  12. Unemployment among breast cancer survivors

    DEFF Research Database (Denmark)

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg

    2014-01-01

    AIM: Though about 20% of working age breast cancer survivors do not return to work after treatment, few studies have addressed risk factors for unemployment. The majority of studies on occupational consequences of breast cancer focus on non-employment, which is a mixture of sickness absence......, unemployment, retirement pensions and other reasons for not working. Unemployment in combination with breast cancer may represent a particular challenge for these women. The aim of the present study is therefore to analyze the risk for unemployment in the years following diagnosis and treatment for breast...... cancer. METHOD: This study included 14,750 women diagnosed with breast cancer in Denmark 2001-2009 identified through a population-based clinical database and linked with information from Danish administrative population based registers for information on labour market affiliation, socio...

  13. The Utility of Phosphohistone H3 in Breast Cancer Grading.

    Science.gov (United States)

    Cui, Xiaoyan; Harada, Shuko; Shen, Dejun; Siegal, Gene P; Wei, Shi

    2015-01-01

    The commonly used Nottingham Grading System in breast cancer takes into consideration the presence of tubular formation, nuclear pleomorphism, and the mitotic index (MI), among which the latter has been shown to be the most powerful prognostic factor. In practice, histologic grading is highly subjective, with only moderate interobserver reproducibility. Phosphorylation of histone H3 has been demonstrated to be a specific event in the mitotic phase, and is negligible during interphase. In this study, we evaluated the efficacy of Phosphohistone H3 (PHH3) in the breast cancer grading of 97 consecutive biopsy specimens. PHH3 antibodies clearly revealed discrete, strong nuclear immunoreactivity in mitotically active cells even under low magnification. The PHH3 MI showed a significant correlation with that derived by hematoxylin and eosin (H&E) staining as well as the Ki-67 proliferation index. Further, the pairwise κ-value of the MI was significantly increased, and the pairwise agreement was also markedly improved by PHH3 immunostaining, although a significant proportion of breast cancer cases were upgraded by use of the PHH3 MI. Our data showed that PHH3 provided a more sensitive and accurate MI with less interobserver variability when compared with conventional H&E staining, thus emphasizing its potentially increased value in practice. Reconsideration of breast cancer grading with integration of PHH3 should be considered if it continues to demonstrate superiorly to traditional H&E staining.

  14. Breast cancer in atomic bomb survivors

    International Nuclear Information System (INIS)

    Tokunga, M.; Land, C.E.; Tokuoka, S.

    1986-01-01

    Thirty eight years after the atomic bombings, studies of the Radiation Effects Research Foundation (RERF) on the extended Life Span Study (LSS) sample have continued to provide important information on radiation carcinogenesis. The third breast cancer survey among this sample revealed 564 cases during the period 1950-80, of which 412 were reviewed microscopically. The following statements reflect the conclusions from the current investigation; 1) the relationship between radiation dose and breast cancer incidence was consistent with linearity and did not differ markedly between the Hiroshima and Nagasaki survivors, 2) a dose-related breast cancer risk was observed among women who were in their first decade of life at the time of exposure, 3) the relative risk of radiationinduced breast cancer decreased with increasing age at exposure, 4) the pattern over time of age-specific breast cancer incidence is similar for exposed and control women (that is, exposed women have more breast cancer than control women but the excess risk closely follows normal risk as expressed by age-specific population rates), and 5) radiation-induced breast cancer appears to be morphologically similar to other breast cancer

  15. Breast cancer in atomic bomb survivors

    International Nuclear Information System (INIS)

    Tokunaga, Masayoshi; Tokuoka, Shoji; Land, C.E.

    1986-01-01

    Thirty eight years after the atomic bombings, studies of the Radiation Effects Research Foundation (RERF) on the extended Life Span Study (LSS) sample have continued to provide important information on radiation carcinogenesis. The third breast cancer survey among this sample revealed 564 cases during the period 1950 - 80, of which 412 were reviewed microscopically. The following statements reflect the conclusions from the current investigation; 1) the relationship between radiation dose and breast cancer incidence was consistent with linearity and did not differ markedly between the Hiroshima and Nagasaki survivors, 2) a dose-related breast cancer risk was observed among women who were in their first decade of life at the time of exposure, 3) the relative risk of radiation-induced breast cancer decreased with increasing age at exposure, 4) the pattern over time of age-specific breast cancer incidence is similar for exposed and control women (that is, exposed women have more breast cancer than control women but the excess risk closely follows normal risk as expressed by age-specific population rates), and 5) radiation-induced breast cancer appears to be morphologically similar to other breast cancer. (author)

  16. Screen-detected versus interval cancers: Effect of imaging modality and breast density in the Flemish Breast Cancer Screening Programme.

    Science.gov (United States)

    Timmermans, Lore; Bleyen, Luc; Bacher, Klaus; Van Herck, Koen; Lemmens, Kim; Van Ongeval, Chantal; Van Steen, Andre; Martens, Patrick; De Brabander, Isabel; Goossens, Mathieu; Thierens, Hubert

    2017-09-01

    To investigate if direct radiography (DR) performs better than screen-film mammography (SF) and computed radiography (CR) in dense breasts in a decentralized organised Breast Cancer Screening Programme. To this end, screen-detected versus interval cancers were studied in different BI-RADS density classes for these imaging modalities. The study cohort consisted of 351,532 women who participated in the Flemish Breast Cancer Screening Programme in 2009 and 2010. Information on screen-detected and interval cancers, breast density scores of radiologist second readers, and imaging modality was obtained by linkage of the databases of the Centre of Cancer Detection and the Belgian Cancer Registry. Overall, 67% of occurring breast cancers are screen detected and 33% are interval cancers, with DR performing better than SF and CR. The interval cancer rate increases gradually with breast density, regardless of modality. In the high-density class, the interval cancer rate exceeds the cancer detection rate for SF and CR, but not for DR. DR is superior to SF and CR with respect to cancer detection rates for high-density breasts. To reduce the high interval cancer rate in dense breasts, use of an additional imaging technique in screening can be taken into consideration. • Interval cancer rate increases gradually with breast density, regardless of modality. • Cancer detection rate in high-density breasts is superior in DR. • IC rate exceeds CDR for SF and CR in high-density breasts. • DR performs better in high-density breasts for third readings and false-positives.

  17. Imaging Management of Breast Density, a Controversial Risk Factor for Breast Cancer.

    Science.gov (United States)

    Falcon, Shannon; Williams, Angela; Weinfurtner, Jared; Drukteinis, Jennifer S

    2017-04-01

    Breast density is well recognized as an independent risk factor for the development of breast cancer. However, the magnitude of risk is controversial. As the public becomes increasingly aware of breast density as a risk factor, legislation and notification laws in relation to breast density have become common throughout the United States. Awareness of breast density as a risk factor for breast cancer presents new challenges for the clinician in the approach to the management and screening of women with dense breasts. The evidence and controversy surrounding breast density as a risk factor for the development of breast cancer are discussed. Common supplemental screening modalities for breast cancer are also discussed, including tomosynthesis, ultrasonography, and magnetic resonance imaging. A management strategy for screening women with dense breasts is also presented. The American College of Radiology recognizes breast density as a controversial risk factor for breast cancer, whereas the American Congress of Obstetricians and Gynecologists recognizes breast density as a modest risk factor. Neither organization recommends the routine use of supplemental screening in women with dense breasts without considering additional patient-related risk factors. Breast density is a poorly understood and controversial risk factor for the development of breast cancer. Mammography is a screening modality proven to reduce breast cancer-related mortality rates and is the single most appropriate tool for population-based screening. Use of supplemental screening modalities should be tailored to individual risk assessment.

  18. Delayed breast reconstruction with implants after invasive breast cancer does not impair prognosis

    DEFF Research Database (Denmark)

    Holmich, L.R.; During, M.; Henriksen, T.F.

    2008-01-01

    We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women......We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women...

  19. Iodide transport and breast cancer.

    Science.gov (United States)

    Poole, Vikki L; McCabe, Christopher J

    2015-10-01

    Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer. © 2015 Society for Endocrinology.

  20. Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China); Zhang, Qunye, E-mail: wz.zhangqy@sdu.edu.cn [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong (China); Li, Guorong, E-mail: grli@sdnu.edu.cn [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China)

    2015-03-13

    As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation.