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Sample records for breast tumorigenesis revelation

  1. SIGNIFICANCE AND CORRELATION OF MAPK/ERK2 AND PI3-K IN HUMAN BREAST TUMORIGENESIS

    Institute of Scientific and Technical Information of China (English)

    MA Ping; LI Bai-lin; ZHANG Ying; SONG Min; SONG Ji-ye

    2006-01-01

    Objective: MAPK ((Mitogen-actived Protein Kinase) and PI3-K (Phosphatidylinositol 3-kinase) pathways have been implicated in the mitogenic pathways regulating cell growth, proliferation, differentiation and transformation and thus involved in tumorigenesis. This study was designed to examined the protein expression, activity and mRNA levels of both ERK and PI3-K in a series of breast tumors and adjacent mammary glands, and to figure out the changes of ERK2 and PI3-K during the dynamic process of breast tumorigenesis. Methods: A series of breast tumors and adjacent mammary glands were collected at surgery, including 37 cases of breast cancer, 6 cases of atypical hyperplasia-breast carcinoma in situ and 15 cases of benign conditions. Western blot, kinase activity assay and RT-PCR were used to detect the protein expression, kinase activity and mRNA level, respectively. Results: The revels of protein, activity and mRNA of ERK2 were elevated during the stages of both initiation and progression. The increasing tendency in breast cancer was equal to atypical hyperplasia -in situ carcinoma, but higher than in benign lesion and adjacent normal mammary gland. PI3-K was activated during the stage of progression of breast cancer. An inverse correlation between the activity of PI3-K and ERK2 in breast cancer was found. Conclusion: Our findings indicate that ERK2 may perform its function during both the stages of breast cancer initiation and breast cancer progression, while PI3-K may exert its effect during the stage of breast cancer progression. Both PI3-k and ERK2 are involved in the tumorigenesis of breast cancer.

  2. Cyr61 promotes breast tumorigenesis and cancer progression

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    Tsai, Miaw-Sheue; Bogart, Daphne F.; Castaneda, Jessica M.; Li, Patricia; Lupu, Ruth

    2002-01-16

    Cyr61, a member of the CCN family of genes, is an angiogenic factor. We have shown that it is overexpressed in invasive and metastatic human breast cancer cells and tissues. Here, we investigated whether Cyr61 is necessary and/or sufficient to bypass the ''normal'' estrogen (E2) requirements for breast cancer cell growth. Our results demonstrate that under E2-depleted condition, Cyr61 is sufficient to induce MCF-7 cells grow in the absence of E2. MCF-7 cells transfected with Cyr61 (MCF-7/Cyr61) became E2-independent but still E2-responsive. On the other hand, MCF-7/vector cells remain E2-dependent. MCF-7/Cyr61 cells acquire an antiestrogen-resistant phenotype, one of the most common clinical occurrences during breast cancer progression. MCF-7/Cyr61 cells are anchorage-independent and capable of forming Matrigel outgrowth patterns in the absence of E2. ERa expression in MCF-7/Cyr61 cells is decreased although still functional. Additionally, MCF-7/Cyr61 cells are tumorigenic in ovariectomized athymic nude mice. The tumors resemble human invasive carcinomas with increased vascularization and overexpression of vascular endothelial growth factor (VEGF). Our results demonstrate that Cyr61 is a tumor-promoting factor and a key regulator of breast cancer progression. This study provides evidence that Cyr61 is sufficient to induce E2-independence and anti-E2 resistance, and to promote invasiveness in vitro, and to induce tumorigenesis in vivo, all of which are characteristics of an aggressive breast cancer phenotype.

  3. MYBBP1A suppresses breast cancer tumorigenesis by enhancing the p53 dependent anoikis

    International Nuclear Information System (INIS)

    Tumor suppressor p53 is mutated in a wide variety of human cancers and plays a critical role in anoikis, which is essential for preventing tumorigenesis. Recently, we found that a nucleolar protein, Myb-binding protein 1a (MYBBP1A), was involved in p53 activation. However, the function of MYBBP1A in cancer prevention has not been elucidated. Relationships between MYBBP1A expression levels and breast cancer progression were examined using patient microarray databases and tissue microarrays. Colony formation, xenograft, and anoikis assays were conducted using cells in which MYBBP1A was either knocked down or overexpressed. p53 activation and interactions between p53 and MYBBP1A were assessed by immunoprecipitation and western blot. MYBBP1A expression was negatively correlated with breast cancer tumorigenesis. In vivo and in vitro experiments using the breast cancer cell lines MCF-7 and ZR-75-1, which expresses wild type p53, showed that tumorigenesis, colony formation, and anoikis resistance were significantly enhanced by MYBBP1A knockdown. We also found that MYBBP1A binds to p53 and enhances p53 target gene transcription under anoikis conditions. These results suggest that MYBBP1A is required for p53 activation during anoikis; therefore, it is involved in suppressing colony formation and the tumorigenesis of breast cancer cells. Collectively, our results suggest that MYBBP1A plays a role in tumor prevention in the context of p53 activation

  4. CHL1 is involved in human breast tumorigenesis and progression

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    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.

  5. CHL1 is involved in human breast tumorigenesis and progression

    International Nuclear Information System (INIS)

    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

  6. Epigenetic regulation of multiple tumor-related genes leads to suppression of breast tumorigenesis by dietary genistein.

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    Yuanyuan Li

    Full Text Available Breast cancer is one of the most lethal diseases in women; however, the precise etiological factors are still not clear. Genistein (GE, a natural isoflavone found in soybean products, is believed to be a potent chemopreventive agent for breast cancer. One of the most important mechanisms for GE inhibition of breast cancer may involve its potential in impacting epigenetic processes allowing reversal of aberrant epigenetic events during breast tumorigenesis. To investigate epigenetic regulation for GE impedance of breast tumorigenesis, we monitored epigenetic alterations of several key tumor-related genes in an established breast cancer transformation system. Our results show that GE significantly inhibited cell growth in a dose-dependent manner in precancerous breast cells and breast cancer cells, whereas it exhibited little effect on normal human mammary epithelial cells. Furthermore, GE treatment increased expression of two crucial tumor suppressor genes, p21(WAF1 (p21 and p16(INK4a (p16, although it decreased expression of two tumor promoting genes, BMI1 and c-MYC. GE treatment led to alterations of histone modifications in the promoters of p21 and p16 as well as the binding ability of the c-MYC-BMI1 complex to the p16 promoter contributing to GE-induced epigenetic activation of these tumor suppressor genes. In addition, an orally-fed GE diet prevented breast tumorigenesis and inhibited breast cancer development in breast cancer mice xenografts. Our results suggest that genistein may repress early breast tumorigenesis by epigenetic regulation of p21 and p16 by impacting histone modifications as well as the BMI1-c-MYC complex recruitment to the regulatory region in the promoters of these genes. These studies will facilitate more effective use of soybean product in breast cancer prevention and also help elucidate the mechanisms during the process of early breast tumorigenesis.

  7. The Rab2A GTPase Promotes Breast Cancer Stem Cells and Tumorigenesis via Erk Signaling Activation

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    Man-Li Luo

    2015-04-01

    Full Text Available Proline-directed phosphorylation is regulated by the prolyl isomerase Pin1, which plays a fundamental role in driving breast cancer stem-like cells (BCSCs. Rab2A is a small GTPase critical for vesicle trafficking. Here, we show that Pin1 increases Rab2A transcription to promote BCSC expansion and tumorigenesis in vitro and in vivo. Mechanistically, Rab2A directly interacts with and prevents dephosphorylation/inactivation of Erk1/2 by the MKP3 phosphatase, resulting in Zeb1 upregulation and β-catenin nuclear translocation. In cancer cells, Rab2A is activated via gene amplification, mutation or Pin1 overexpression. Rab2A overexpression or mutation endows BCSC traits to primary normal human breast epithelial cells, whereas silencing Rab2A potently inhibits the expansion and tumorigenesis of freshly isolated BCSCs. Finally, Rab2A overexpression correlates with poor clinical outcome in breast cancer patients. Thus, Pin1/Rab2A/Erk drives BCSC expansion and tumorigenicity, suggesting potential drug targets.

  8. Vitamin D3-dependent VDR signaling delays ron-mediated breast tumorigenesis through suppression of β-catenin activity

    OpenAIRE

    Johnson, Abby L.; Zinser, Glendon M.; Waltz, Susan E.

    2015-01-01

    The Ron receptor is upregulated in human breast cancers and correlates with enhanced metastasis and reduced patient survival. Ron overexpression drives mammary tumorigenesis through direct β-catenin activation and augmented tumor cell proliferation, migration and invasion. Ron and β-catenin are also coordinately elevated in breast cancers. The vitamin D receptor (VDR) antagonizes β-catenin signaling. Herein, we examined mammary tumor onset and progression using a Ron-driven murine model of br...

  9. Progressive loss of anti-HER2 CD4+ T-helper type 1 response in breast tumorigenesis and the potential for immune restoration

    OpenAIRE

    Datta, Jashodeep; Rosemblit, Cinthia; Berk, Erik; Showalter, Lori; Namjoshi, Prachi; Mick, Rosemarie; Lee, Kathreen P; Brod, Andrew M; Yang, Rachel L; Kelz, Rachel R; Fitzpatrick, Elizabeth; Hoyt, Clifford; Feldman, Michael D.; Zhang, Paul J.; Xu, Shuwen

    2015-01-01

    Genomic profiling has identified several molecular oncodrivers in breast tumorigenesis. A thorough understanding of endogenous immune responses to these oncodrivers may provide insights into immune interventions for breast cancer (BC). We investigated systemic anti-HER2/neu CD4+ T-helper type-1 (Th1) responses in HER2-driven breast tumorigenesis. A highly significant stepwise Th1 response loss extending from healthy donors (HD), through HER2pos-DCIS, and ultimately to early stage HER2pos-inva...

  10. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    International Nuclear Information System (INIS)

    Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis

  11. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

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    Cai Shao-xi

    2011-03-01

    Full Text Available Abstract Background Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Methods Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. Results In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. Conclusion These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

  12. Vitamin D3-dependent VDR signaling delays ron-mediated breast tumorigenesis through suppression of β-catenin activity.

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    Johnson, Abby L; Zinser, Glendon M; Waltz, Susan E

    2015-06-30

    The Ron receptor is upregulated in human breast cancers and correlates with enhanced metastasis and reduced patient survival. Ron overexpression drives mammary tumorigenesis through direct β-catenin activation and augmented tumor cell proliferation, migration and invasion. Ron and β-catenin are also coordinately elevated in breast cancers. The vitamin D receptor (VDR) antagonizes β-catenin signaling. Herein, we examined mammary tumor onset and progression using a Ron-driven murine model of breast tumorigenesis crossed with VDR deficient mice. VDR ablation accelerated mammary tumor onset and led to tumors that exhibited a desmoplastic phenotype and enhanced metastases. Tumor levels of active β-catenin were markedly increased in the absence of VDR. In vitro, VDR activation in breast cancer cells reduced β-catenin activation and transcriptional activity leading to elevated expression of the extracellular Wnt inhibitor dickkopf-related protein 1, and a reduction in the interaction of β-catenin with the cyclin D1 promoter. Expression of a stabilized form or β-catenin ablated the protective effects of VDR activation.Collectively, these studies delineate a protective role for VDR signaling in Ron-induced mammary tumorigenesis through disruption of β-catenin activation. PMID:26008979

  13. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

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    Hoshiba, Takashi [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan); International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Tanaka, Masaru, E-mail: tanaka@yz.yamagata-u.ac.jp [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan)

    2013-09-20

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

  14. The Cell Surface Estrogen Receptor, G Protein- Coupled Receptor 30 (GPR30, is Markedly Down Regulated During Breast Tumorigenesis

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    Indira Poola

    2008-01-01

    Full Text Available Background: GPR30 is a cell surface estrogen receptor that has been shown to mediate a number of non-genomic rapid effects of estrogen and appear to balance the signaling of estrogen and growth factors. In addition, progestins appear to use GPR30 for their actions. Therefore, GPR30 could play a critical role in hormonal regulation of breast epithelial cell integrity. Deregulation of the events mediated by GPR30 could contribute to tumorigenesis.Methods: To understand the role of GPR30 in the deregulation of estrogen signaling processes during breast carcinogenesis, we have undertaken this study to investigate its expression at mRNA levels in tumor tissues and their matched normal tissues. We compared its expression at mRNA levels by RT quantitative real-time PCR relative to GAPDH in ERα”—positive (n = 54 and ERα”—negative (n = 45 breast cancer tissues to their matched normal tissues.Results: We report here, for the first time, that GPR30 mRNA levels were significantly down-regulated in cancer tissues in comparison with their matched normal tissues (p 0.0001 by two sided paired t-test. The GPR30 expression levels were significantly lower in tumor tissues from patients (n = 29 who had lymph node metastasis in comparison with tumors from patients (n = 53 who were negative for lymph node metastasis (two sample t-test, p 0.02, but no association was found with ERα, PR and other tumor characteristics.Conclusions: Down-regulation of GPR30 could contribute to breast tumorigenesis and lymph node metastasis.

  15. The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression

    International Nuclear Information System (INIS)

    E-cadherin is a cell–cell adhesion protein fulfilling a prominent role in epithelial differentiation. Data from model systems suggest that E-cadherin is a potent invasion/tumor suppressor of breast cancer. Consistent with this role in breast cancer progression, partial or complete loss of E-cadherin expression has been found to correlate with poor prognosis in breast cancer patients. The E-cadherin gene (CDH1) is located on human chromosome 16q22.1, a region frequently affected with loss of heterozygosity in sporadic breast cancer. Invasive lobular breast carcinomas, which are typically completely E-cadherin-negative, often show inactivating mutations in combination with loss of heterozygosity of the wild-type CDH1 allele. Mutations were found at early noninvasive stages, thus associating E-cadherin mutations with loss of cell growth control and defining CDH1 as the tumor suppressor for the lobular breast cancer subtype. Ductal breast cancers in general show heterogeneous loss of E-cadherin expression, associated with epigenetic transcriptional downregulation. It is proposed that the microenvironment at the invasive front is transiently downregulating E-cadherin transcription. This can be associated with induction of nonepithelial cadherins

  16. Progesterone receptors – animal models and cell signaling in breast cancer: The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis

    International Nuclear Information System (INIS)

    A relatively small number of cells in the normal human mammary gland express receptors for oestrogen and progesterone (ER and PR), and there is almost complete dissociation between steroid receptor expression and proliferation. Increased expression of the ER alpha (ERα) and loss of the inverse relationship between receptor expression and proliferation occur at the very earliest stages of tumorigenesis, implying that dysregulation of ERα expression contributes to breast tumour formation. There is evidence also for alterations in the ratio between the two PR isoforms in premalignant breast lesions. Elucidation of the factors mediating the effects of oestradiol and progesterone on development of the normal breast and of the mechanisms by which expression of the ERα and the PR isoforms is controlled could identify new targets for breast cancer prevention and improved prediction of breast cancer risk

  17. Role of HGF in obesity-associated tumorigenesis: C3(1)-TAg mice as a model for human basal-like breast cancer

    OpenAIRE

    Sundaram, Sneha; Freemerman, Alex J.; Johnson, Amy R.; Milner, J. Justin; McNaughton, Kirk K.; Galanko, Joseph A.; Bendt, Katharine M.; Darr, David B.; Charles M Perou; Melissa A Troester; Makowski, Liza

    2013-01-01

    Obesity is associated with basal-like breast cancer (BBC), an aggressive breast cancer subtype. The objective of this study was to determine whether obesity promotes BBC onset in adulthood and to evaluate the role of stromal-epithelial interactions in obesity-associated tumorigenesis. We hypothesized that hepatocyte growth factor (HGF) plays a promoting role in BBC, which express the HGF receptor, c-Met. In C3(1)-Tag mice, a murine model of BBC, we demonstrated that obesity leads to a signifi...

  18. MicroRNA-490 inhibits tumorigenesis and progression in breast cancer

    OpenAIRE

    Zhao L; Zheng XY

    2016-01-01

    Lin Zhao,1 Xin-Yu Zheng1,21Department of Breast Surgery, the First Hospital of China Medical University, 2The First Laboratory, Cancer Institute of China Medical University, Shenyang, People’s Republic of ChinaAbstract: MicroRNAs are consistently reported to regulate gene expression in all cancer cell types by modulating a wide range of biological processes, including cell proliferation, differentiation, and apoptosis, which are associated with tumor development and progression. Previou...

  19. A Comparative Analysis of Genetic and Epigenetic Events of Breast and Ovarian Cancer Related to Tumorigenesis

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    Mckenna Longacre

    2016-05-01

    Full Text Available Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance.

  20. A Comparative Analysis of Genetic and Epigenetic Events of Breast and Ovarian Cancer Related to Tumorigenesis

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    Longacre, Mckenna; Snyder, Nicole A.; Housman, Genevieve; Leary, Meghan; Lapinska, Karolina; Heerboth, Sarah; Willbanks, Amber; Sarkar, Sibaji

    2016-01-01

    Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance. PMID:27213343

  1. Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis

    International Nuclear Information System (INIS)

    Overexpression of the HER2/neu gene in breast cancer is associated with an increased incidence of metastatic disease and with a poor prognosis. Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective. Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model. VRP-neu prevented or significantly inhibited the growth of HER2/neu-expressing murine breast cancer cells injected either into mammary tissue or intravenously. Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8+ T lymphocytes and serum IgG. On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu+ breast cancer is warranted

  2. Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis

    Science.gov (United States)

    Stewart, Michael K. G.; Plante, Isabelle; Penuela, Silvia; Laird, Dale W.

    2016-01-01

    Pannexin1 (Panx1) subunits oligomerize to form large-pore channels between the intracellular and extracellular milieu that have been shown to regulate proliferation, differentiation and cell death mechanisms. These key cellular responses are ultimately necessary for normal tissue development and function but the role of Panx1 in development, differentiation and function in many tissues remains unexplored, including that of the breast. Panx1 was identified to be expressed in the mammary gland through western blot and immunofluorescent analysis and is dynamically upregulated during pregnancy and lactation. In order to evaluate the role of Panx1 in the context of mammary gland development and function, Panx1-/- mice were evaluated in comparison to wild-type mice in the mammary glands of virgin, lactating and involuting mice. Our results revealed that Panx1 ablation did not affect virgin or involuting mammary glands following histological and whole mount analysis. Panx1 was necessary for timely alveolar development during early lactation based on a decreased number of alveolar lumen following histological analysis and reduced proliferation following Ki67 immunofluorescent labelling. Importantly, the loss of Panx1 in lactating mammary glands did not overtly affect epithelial or secretory differentiation of the mammary gland suggesting that Panx1 is not critical in normal mammary gland function. In addition, PANX1 mRNA expression was correlated with negative clinical outcomes in patients with breast cancer using in silico arrays. Together, our results suggest that Panx1 is necessary for timely alveolar development following the transition from pregnancy to lactation, which may have implications extending to patients with breast cancer. PMID:27099931

  3. The Models of Revelational Communication

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    S. Mahdi Lotfi

    2012-05-01

    Full Text Available   Quranic revelation is a verbal communication between the Prophet and God which is in the communication model includes sender, recipient, purpose and channels of communication. Muslim scholars and some of the orientalists, offering a variety of communication models that can be investigated in the form of linear and nonlinear models. Linear models contains different elements of revelated communication and attempt to draw process of sending revelation. Some part of this models have a structural fault. nonlinear models also drawing the process of prophet soul ascending and take a different process for sending of revelation but ascending soul of prophet oppose with quran, traditions and communication principles. This type of models is also deficient and weak. This paper review the different models of communication and criticize them from quranic and hadiths point of view .

  4. The Models of Revelational Communication

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    Lotfi, S.M

    2012-01-01

    Full Text Available Quranic revelation is a verbal communication between the Prophet and God which is in the communication model includes sender, recipient, purpose and channels of communication. Muslim scholars and some of the orientalists, offering a variety of communication models that can be investigated in the form of linear and nonlinear models. Linear models contains different elements of revelated communication and attempt to draw process of sending revelation. Some part of this models have a structural fault. nonlinear models also drawing the process of prophet soul ascending and take a different process for sending of revelation but ascending soul of prophet oppose with quran, traditions and communication principles. This type of models is also deficient and weak. This paper review the different models of communication and criticize them from quranic and hadiths point of view.

  5. Interaction of CDCP1 with HER2 Enhances HER2-Driven Tumorigenesis and Promotes Trastuzumab Resistance in Breast Cancer

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    Abdullah Alajati

    2015-04-01

    Full Text Available Understanding the molecular pathways that contribute to the aggressive behavior of HER2-positive breast cancers may aid in the development of novel therapeutic interventions. Here, we show that CDCP1 and HER2 are frequently co-overexpressed in metastatic breast tumors and associated with poor patient prognosis. HER2 and CDCP1 co-overexpression leads to increased transformation ability, cell migration, and tumor formation in vivo, and enhanced HER2 activation and downstream signaling in different breast cancer cell lines. Mechanistically, we demonstrate that CDCP1 binds to HER2 through its intracellular domain, thereby increasing HER2 interaction with the non-receptor tyrosine kinase c-SRC (SRC, leading to trastuzumab resistance. Taken together, our findings establish that CDCP1 is a modulator of HER2 signaling and a biomarker for the stratification of breast cancer patients with poor prognosis. Our results also provide a rationale for therapeutic targeting of CDCP1 in HER2-positive breast cancer patients.

  6. The direct effect of Focal Adhesion Kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

    International Nuclear Information System (INIS)

    Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis. To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible) system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD), and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation in vitro, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD in vivo, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors. Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability in vitro and inhibited tumorigenesis in vivo. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p < 0.05) by FAKsiRNA. Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis in vivo and reveal specific expression of genes affected by

  7. The direct effect of Focal Adhesion Kinase (FAK, dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2009-08-01

    Full Text Available Abstract Background Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis. Methods To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD, and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation in vitro, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD in vivo, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors. Results Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability in vitro and inhibited tumorigenesis in vivo. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p Conclusion Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis in vivo and reveal

  8. The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis

    OpenAIRE

    Ben-David, Uri; Ha, Gavin; Khadka, Prasidda; Jin, Xin; Wong, Bang; Franke, Lude; Golub, Todd R.

    2016-01-01

    Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45 mouse models, providing the first comprehensive catalogue of chromosomal aberrations in cancer GEMMs. Mining this resource, we find that most chromosomal aberrations accumulate late during breast tu...

  9. Prolyl isomerase Pin1 negatively regulates the stability of SUV39H1 to promote tumorigenesis in breast cancer.

    Science.gov (United States)

    Khanal, Prem; Kim, Garam; Lim, Sung-Chul; Yun, Hyo-Jeong; Lee, Kwang Youl; Choi, Hoo-Kyun; Choi, Hong Seok

    2013-11-01

    Pin1, a conserved eukaryotic peptidyl-prolyl cis/trans isomerase, has profound effects on numerous key-signaling molecules, and its deregulation contributes to disease, particularly cancer. Although Pin1-mediated prolyl isomerization of protein servers as a regulatory switch in signaling pathways, the significance of proline isomerase activity in chromatin modifying complex remains unclear. Here, we identify Pin1 as a key negative regulator for suppressor of variegation 3-9 homologue 1 (SUV39H1) stability, a major methyltransferase responsible for histone H3 trimethylation on Lys9 (H3K9me3). Pin1 interacts with SUV39H1 in a phosphorylation-dependent manner and promotes ubiquitination-mediated degradation of SUV39H1. Consequently, Pin1 reduces SUV39H1 abundance and suppresses SUV39H1 ability to induce H3K9me3. In contrast, depletion of Pin1 in cancer cells leads to elevated SUV39H1 expression, which subsequently increases H3K9me3, inhibiting tumorigenecity of cancer cells. In a xenograft model with 4T1 metastatic mouse breast carcinoma cells, Pin1 overexpression increases tumor growth, whereas SUV39H1 overexpression abrogates it. In human breast cancer patients, immunohistochemical staining shows that Pin1 levels are negatively correlated with SUV39H1 as well as H3K9me3 levels. Thus, Pin1-mediated reduction of SUV39H1 stability contributes to convey oncogenic signals for aggressiveness of human breast cancer, suggesting that Pin1 may be a promising drug target for anticancer therapy. PMID:23934277

  10. Cosmic Revelation: Making Astroparticles Visible

    Science.gov (United States)

    Roth, T. O.; Haungs, A.; Schieler, H.; Weindl, A.

    2010-06-01

    Cosmic Revelation is a prime example of a successful art and science project connecting art and astroparticle physics. One of the main reasons for its success might be that the collaboration between the KArlsruhe Shower Core and Array DEtector (KASCADE) experiment and Tim Otto Roth is both a minimalist light art project and a scientific experiment. In a field of 16 flashing mirror sculptures connected to the KASCADE detector field at KIT (Karlsruhe Institute of Technology, Germany) the impact of high energy cosmic rays on Earth can be experienced directly. In just one year the project has developed from the initial concept to its first presentation in a public space in autumn 2008. We explain how the project developed, and also highlight the practical and conceptual conditions for its realisation.

  11. Revelation and Innovation of Value

    DEFF Research Database (Denmark)

    Saghaug, Kristin Margrethe

    show that many of the business owners in this study try to balance between their personal values and economic values. A further investigation into this results in a model of innovation of value from a theological perspective in respect to business model innovation. It is the very understanding......Kristin F. Saghaug’s Phd thesis investigates the interaction of revelatory theology, artistic creativity and small business owners in a business model innovation context. This project challenges mainstream business management’s concept of value and adds to the understanding of the innovation...... process through a pioneering conversation across different specialized domains. How can philosophical theology, namely, Paul Tillich’s theory of revelation, contribute to productive reflection on the innovation of value among small business owners in a business model innovation context? Empirical findings...

  12. The parity-related protection against breast cancer is compromised by cigarette smoke during rat pregnancy: observations on tumorigenesis and immunological defenses of the neonate.

    OpenAIRE

    Steinetz, Bernard G.; Gordon, Terry; Lasano, Salamia; Horton, Lori; Ng, Sheung Pui; Zelikoff, Judith T.; Nadas, Arthur; Bosland, Maarten C.

    2006-01-01

    Lifestyle modulation of cancer & cancer biomarkersLifestyle element evaluated: early pregnancyOutcome studied (cancer or cancer biomarker): breast cancerMethod of biomarker analysis: hormone assays, cytokine assays, lymphocyte proliferation assayStudy type (in vitro, animals, humans): Sprague-Dawley rats Confounders controlled for: smoking Impact on outcome: (P < 0.005) decrease in serum immunoactive prolactin concentration on Day 19 of pregnancy in the rats exposed to CS as compared with FA...

  13. Binding of anterior gradient 2 and estrogen receptor-α: Dual critical roles in enhancing fulvestrant resistance and IGF-1-induced tumorigenesis of breast cancer.

    Science.gov (United States)

    Li, Zheqi; Zhu, Qi; Chen, Hao; Hu, Lingyun; Negi, Hema; Zheng, Yun; Ahmed, Yeasin; Wu, Zhenghua; Li, Dawei

    2016-07-10

    Anterior gradient 2 (AGR2), an essential cancer biomarker, has been widely reported to be associated with estrogen receptor (ER) positive breast cancer development. Here, we uncovered the role of cytoplasmic and exogenous AGR2, through interaction with ER-α, in enhancing fulvestrant resistance and IGF-1-induced carcinogenesis respectively. Our present study revealed that the endogenous AGR2 level positively correlates with fulvestrant resistance in MCF-7 and T47D cells. AGR2-knockdown in MCF-7 cells strongly enhances the fulvestrant-induced G1 phase arrest and accelerates the fulvestrant-induced ER-α degradation. Furthermore, intracellular AGR2 exhibits a functional interaction with ER-α. On the other hand, extracellular AGR2 remarkably promotes the IGF-1-induced cell proliferation, migration, cell cycle progression and epithelial-mesenchymal transition. Extracellular AGR2 also enhances IGF-1 downstream signaling. We also showed that ER-α specifically interacts with both extracellular AGR2 and IGF-1 receptor as a potential intermediator. Finally, we revealed that the adjuvant therapy of AGR2 monoclonal antibody enhances the inhibitory effects of fulvestrant and linsitinib toward breast cancer development. Our findings, for the first time, point out the different functions of intra- and extra-cellular AGR2, providing new insights into the development of anti-tumor therapies targeting AGR2. PMID:27063095

  14. Ambient oxygen promotes tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Ho Joong Sung

    Full Text Available Oxygen serves as an essential factor for oxidative stress, and it has been shown to be a mutagen in bacteria. While it is well established that ambient oxygen can also cause genomic instability in cultured mammalian cells, its effect on de novo tumorigenesis at the organismal level is unclear. Herein, by decreasing ambient oxygen exposure, we report a ∼50% increase in the median tumor-free survival time of p53-/- mice. In the thymus, reducing oxygen exposure decreased the levels of oxidative DNA damage and RAG recombinase, both of which are known to promote lymphomagenesis in p53-/- mice. Oxygen is further shown to be associated with genomic instability in two additional cancer models involving the APC tumor suppressor gene and chemical carcinogenesis. Together, these observations represent the first report directly testing the effect of ambient oxygen on de novo tumorigenesis and provide important physiologic evidence demonstrating its critical role in increasing genomic instability in vivo.

  15. Kuidas kirjutatakse ajalugu? / Jacques Revel ; interv. Marek Tamm

    Index Scriptorium Estoniae

    Revel, Jacques

    2007-01-01

    Prantsuse ajaloolase ja ajakirja Annales ühe peatoimetaja J. Revel'i erialasest tegevusest ja teostest. Varem. ilm.: Sündmused, jutustus ja analüüsiskaalad : intervjuu Jacques Reveliga // Revel, Jacques, Farge, Arlette. Mässu loogika : lasteröövlite afäär Pariisis 1750. - Tallinn, 2005. - Lk. 109-123

  16. Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis

    OpenAIRE

    Hulit, James; Di Vizio, Dolores; Pestell, Richard G.

    2001-01-01

    Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targeted expression of oncogenic Ras or c-Myc is sufficient for the induction of mammary gland tumorigenesis in the rodent, and when overexpressed together the rate of tumor onset is...

  17. Cosmology in the book of Revelation

    Directory of Open Access Journals (Sweden)

    Gert J.C. Jordaan

    2013-06-01

    Full Text Available The cosmology of the book of Revelation mainly involves God’s restored reign over the created universe (κόσμος. Throughout the book, the κόσμος is depicted according to its constituent parts, namelyheaven, sea and earth. At first sight, this threefold description seems to stem from the ancient Jewish and mythological three-storied cosmological view of ‘up-above’, ‘here-below’ and ‘down-under’. However, this correspondence proves to be only superficial. Heaven is used by John not as much in spatial sense as in temporal sense: as symbolic reference to a divine point above time and history. Heaven is also a qualitative reference to a situation of complete obedient worship to God. Earth in John’s visions is mostly used as metaphor for sinful mankind under the rule of Satan. Yet, the earth remains part of God’s creation under his divine authority, and even becomes a refuge for the church in this dispensation. The sea in Revelation, when not denoting a physical space, is often equated by scholars to the abyss or the underworld. However, in Revelation the sea is mostly used as metaphor for the basic evil from which the beast originates and of everything immoral and impure. The last chapters of Revelation reveal that in the eschaton heaven, sea and earth will all be part of the new creation − renewed to the point where God’s reign is restored and acknowledged above all doubt throughout the κόσμος.Kosmologie in die boek van Openbaring. Die kosmologie van Openbaring getuig van God se herstelde regering oor die geskape heelal (κόσμος. Regdeur die boek word die κόσμος volgens sy samestellende dele beskryf, naamlik hemel, see en aarde. Oppervlakkig beskou, lyk hierdie beskrywing na die antieke Joodse en mitologiese drie-verdieping-kosmologie van ‘daar bo’, ‘hier onder’ en ‘daar onder’. Hierdie ooreenkoms is egter slegs oppervlakkig. Hemel word deur Johannes nie soseer in ruimtelike sin

  18. 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.

  19. Naturally-occurring estradiol-17β-fatty acid esters, but not estradiol-17β, preferentially induce mammary tumorigenesis in female rats: Implications for an important role in human breast cancer

    International Nuclear Information System (INIS)

    Because mammary glands are surrounded by adipose tissues, we hypothesize that the ultra-lipophilic endogenous estrogen-17β-fatty acid esters may have preferential hormonal and carcinogenic effects in mammary tissues compared to other target organs (such as the uterus and pituitary). This hypothesis is tested in the present study. We found that all 46 rats implanted with an estradiol-17β pellet developed large pituitary tumors (average weight = 251 ±103 mg) and had to be terminated early, but only 48% of them developed mammary tumors. In addition, approximately one-fourth of them developed a huge uterus. In the 26 animals implanted with a mixture containing estradiol-17β-stearate and estradiol-17β-palmitate (two representative estradiol-17β-fatty acid esters) or in the 29 animals implanted with estradiol-17β-stearate alone (in the same molar dose as estradiol-17β), 73% and 79%, respectively, of them developed mammary tumors, whereas only 3 or 2 animals, respectively, had to be terminated early due to the presence of a large pituitary tumor. Both tumorous and normal mammary tissues contained much higher levels of estrogen esterase than other tissues, which catalyzes the releases of bioactive estrogens from their fatty acid esters. In conclusion, while estradiol-17β is much stronger in inducing pituitary tumor (100% incidence) than mammary tumor, estradiol-17β-fatty acid esters have a higher efficacy than estradiol-17β in inducing mammary tumor and yet it only has little ability to induce uterine out-growth and pituitary tumorigenesis. This study establishes the endogenous estrogen-17β-fatty acid esters as preferential inducers of mammary tumorigenesis

  20. Loss of KLF14 triggers centrosome amplification and tumorigenesis.

    Science.gov (United States)

    Fan, Guangjian; Sun, Lianhui; Shan, Peipei; Zhang, Xianying; Huan, Jinliang; Zhang, Xiaohong; Li, Dali; Wang, Tingting; Wei, Tingting; Zhang, Xiaohong; Gu, Xiaoyang; Yao, Liangfang; Xuan, Yang; Hou, Zhaoyuan; Cui, Yongping; Cao, Liu; Li, Xiaotao; Zhang, Shengping; Wang, Chuangui

    2015-01-01

    Centrosome amplification is frequent in cancer, but the underlying mechanisms remain unclear. Here we report that disruption of the Kruppel-like factor 14 (KLF14) gene in mice causes centrosome amplification, aneuploidy and spontaneous tumorigenesis. Molecularly, KLF14 functions as a transcriptional repressor of Plk4, a polo-like kinase whose overexpression induces centrosome overduplication. Transient knockdown of KLF14 is sufficient to induce Plk4-directed centrosome amplification. Clinically, KLF14 transcription is significantly downregulated, whereas Plk4 transcription is upregulated in multiple types of cancers, and there exists an inverse correlation between KLF14 and Plk4 protein expression in human breast and colon cancers. Moreover, KLF14 depletion promotes AOM/DSS-induced colon tumorigenesis. Our findings reveal that KLF14 reduction serves as a mechanism leading to centrosome amplification and tumorigenesis. On the other hand, forced expression of KLF14 leads to mitotic catastrophe. Collectively, our findings identify KLF14 as a tumour suppressor and highlight its potential as biomarker and therapeutic target for cancer. PMID:26439168

  1. 28 CFR 22.22 - Revelation of identifiable data.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Revelation of identifiable data. 22.22 Section 22.22 Judicial Administration DEPARTMENT OF JUSTICE CONFIDENTIALITY OF IDENTIFIABLE RESEARCH AND... subject, be expected to totally conceal subject identity....

  2. Unstructuring User Preferences: Efficient Non-Parametric Utility Revelation

    OpenAIRE

    Domshlak, Carmel; Joachims, Thorsten

    2012-01-01

    Tackling the problem of ordinal preference revelation and reasoning, we propose a novel methodology for generating an ordinal utility function from a set of qualitative preference statements. To the best of our knowledge, our proposal constitutes the first nonparametric solution for this problem that is both efficient and semantically sound. Our initial experiments provide strong evidence for practical effectiveness of our approach.

  3. Conditions affecting the revelation effect for autobiographical memory.

    Science.gov (United States)

    Bernstein, Daniel M; Godfrey, Ryan D; Davison, Arienne; Loftus, Elizabeth F

    2004-04-01

    In four experiments involving 184 participants, people rated their confidence that particular events had happened in their childhood (e.g., "Broke a window playing ball"). If participants had to unscramble a key word in a phrase just before rating it (e.g., "Broke a nwidwo [window] playing ball"), confidence ratings increased-the revelation effect. However, the pattern of revelation effects depended on the particular way in which participants processed key words (e.g., visualizing vs. counting vowels in the word window) approximately 10 min prior to rating life events that contained those words. Prior exposure to key words never in itself directly affected confidence ratings. These results demonstrate that one can manipulate the revelation effect by altering the processing that participants perform on words prior to unscrambling them. These results also pose difficulties for many accounts of the revelation effect. The major puzzle posed by our present findings is that unscrambling key words increases confidence that an event has happened in childhood, whereas prior exposure to these words does not. PMID:15285128

  4. Breast

    International Nuclear Information System (INIS)

    Ultrasound is not an efficacious screening modality to detect early-stage breast malignancy in a clinically unremarkable population of women. Computed body tomography is similarly not practical for screening because of slice thickness and partial volume averaging, a higher radiation dose than modern mammography, and the lack of availability of such units for such a high throughput requirement. Nevertheless, these two imaging modalities can be very useful in management to guide the least invasive and efficacious treatment of the patient. X-ray mammography remains the principal imaging modality in the search for breast malignancy, but ultrasound is the single most important second study in the diagnostic evaluation of the breast. The combined use of these techniques and the ability to perform guided aspiration and localization procedures can result in a reduction in the surgical removal of benign cysts and reduction in the amount of tissue volume required if excision becomes necessary

  5. The interplay between autophagy and ROS in tumorigenesis

    Directory of Open Access Journals (Sweden)

    VassilikiKarantza

    2012-11-01

    Full Text Available Reactive oxygen species (ROS at physiological levels are important cell signaling molecules. However, aberrantly high ROS are intimately associated with disease and commonly observed in cancer. Mitochondria are primary sources of intracellular ROS, and their maintenance is essential to cellular health. Autophagy, an evolutionarily conserved process whereby cytoplasmic components are delivered to lysosomes for degradation, is responsible for mitochondrial turnover and removal of damaged mitochondria. Impaired autophagy is implicated in many pathological conditions, including neurological disorders, inflammatory bowel disease, diabetes, aging and cancer. The first reports connecting autophagy to cancer showed that allelic loss of the essential autophagy gene BECLIN1 (BECN1 is prevalent in human breast, ovarian and prostate cancers and that Becn1+/- mice develop mammary gland hyperplasias, lymphomas, and lung and liver tumors. Subsequent studies demonstrated that Atg5-/- and Atg7-/- livers give rise to adenomas, Atg4-/- mice are susceptible to chemical carcinogenesis, and Bif1-/- mice are prone to spontaneous tumors, indicating that autophagy defects promote tumorigenesis. Due to defective mitophagy, autophagy-deficient cells accumulate damaged mitochondria and deregulated ROS levels, which likely contribute to their tumor-initiating capacity. However, the role of autophagy in tumorigenesis is complex, as more recent work also revealed tumor dependence on autophagy: autophagy-competent mutant-Ras-expressing cells form tumors more efficiently than their autophagy-deficient counterparts; similarly, FIP200 deficiency suppresses PyMT-driven mammary tumorigenesis. These latter findings are attributed to the fact that tumors driven by powerful oncogenes have high metabolic demands catered to by autophagy. In this review, we discuss the relationship between ROS and autophagy and summarize our current knowledge on their functional interactions in

  6. Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis

    International Nuclear Information System (INIS)

    Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targeted expression of oncogenic Ras or c-Myc is sufficient for the induction of mammary gland tumorigenesis in the rodent, and when overexpressed together the rate of tumor onset is substantially enhanced. In an exciting recent finding, D'Cruz et al discovered tetracycline-regulated c-Myc overexpression in the mammary gland induced invasive mammary tumors that regressed upon withdrawal of c-Myc expression. Almost one-half of the c-Myc-induced tumors harbored K-ras or N-ras gene point mutations, correlating with tumor persistence on withdrawal of c-Myc transgene expression. These findings suggest maintenance of tumorigenesis may involve a second mutation within the Ras pathway

  7. Reproduction and Breast Cancer Risk

    OpenAIRE

    Hanf, Volker; Hanf, Dorothea

    2014-01-01

    Reproduction is doubtlessly one of the main biological meanings of life. It is therefore not surprising that various aspects of reproduction impact on breast cancer risk. Various developmental levels may become targets of breast tumorigenesis. This review follows the chronologic sequence of events in the life of a female at risk, starting with the intrauterine development. Furthermore, the influence of both contraceptive measures and fertility treatment on breast cancer development is dealt w...

  8. BAG-1 haplo-insufficiency impairs lung tumorigenesis

    Directory of Open Access Journals (Sweden)

    Camarero Guadalupe

    2004-11-01

    Full Text Available Abstract Background BAG-1 is a multifunctional co-chaperone of heat shock proteins (Hsc70/Hsp70 that is expressed in most cells. It interacts with Bcl-2 and Raf indicating that it might connect protein folding with other signaling pathways. Evidence that BAG-1 expression is frequently altered in human cancers, in particular in breast cancer, relative to normal cells has been put forward but the notion that overexpression of BAG-1 contributes to poor prognosis in tumorigenesis remains controversial. Methods We have evaluated the effect of BAG-1 heterozygosity in mice in a model of non-small-cell lung tumorigenesis with histological and molecular methods. We have generated mice heterozygous for BAG-1, carrying a BAG-1 null allele, that in addition express oncogenic, constitutively active C-Raf kinase (SP-C C-Raf BxB in type II pneumocytes. SP-C C-Raf BxB mice develop multifocal adenomas early in adulthood. Results We show that BAG-1 heterozygosity in mice impairs C-Raf oncogene-induced lung adenoma growth. Lung tumor initiation was reduced by half in BAG-1 heterozygous SP-C C-Raf BxB mice compared to their littermates. Tumor area was reduced by 75% in 4 month lungs of BAG-1 haploinsufficient mice compared to mice with two BAG-1 copies. Whereas BAG-1 heterozygosity did not affect the rate of cell proliferation or signaling through the mitogenic cascade in adenoma cells, it increased the rate of apoptosis. Conclusion Reduced BAG-1 expression specifically targets tumor cells to apoptosis and impairs tumorigenesis. Our data implicate BAG-1 as a key player in oncogenic transformation by Raf and identify it as a potential molecular target for cancer treatment.

  9. Anaplastic thyroid cancer, tumorigenesis and therapy.

    LENUS (Irish Health Repository)

    O'Neill, J P

    2010-03-01

    Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

  10. The roles of PIKE in tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Qi QI; Keqiang YE

    2013-01-01

    Tumorigenesis is the process by which normal cells evolve the capacity to evade and overcome the constraints usually placed upon their growth and survival.To ensure the integrity of organs and tissues,the balance of cell proliferation and cell death is tightly maintained.The proteins controlling this balance are either considered oncogenes,which promote tumorigenesis,or tumor suppressors,which prevent tumorigenesis.Phosphoinositide 3-kinase enhancer (PIKE) is a family of GTP-binding proteins that possess anti-apoptotic functions and play an important role in the central nervous system.Notably,accumulating evidence suggests that PIKE is a proto-oncogene involved in tumor progression.The PIKE gene (CENTG1) is amplified in a variety of human cancers,leading to the resistance against apoptosis and the enhancement of invasion.In this review,we will summarize the functions of PIKE proteins in tumorigenesis and discuss their potential implications in cancer therapy.

  11. PUMA Suppresses Intestinal Tumorigenesis in Mice

    OpenAIRE

    Qiu, Wei; Carson-Walter, Eleanor B.; Kuan, Shih Fan; Zhang, Lin; Yu, Jian

    2009-01-01

    Defective apoptosis contributes to tumorigenesis, although the critical molecular targets remain to be fully characterized. PUMA, a BH3-only protein essential for p53-dependent apoptosis, has been shown to suppress lymphomagenesis. In this study, we investigated the role of PUMA in intestinal tumorigenesis using two animal models. In the azoxymethane (AOM)/dextran sulfate sodium salt model, PUMA deficiency increased the multiplicity and size of colon tumors but reduced the frequency of β-cate...

  12. Cancer Stem Cells in Lung Tumorigenesis

    OpenAIRE

    Kratz, Johannes R.; Yagui-Beltrán, Adam; Jablons, David M.

    2010-01-01

    Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continue...

  13. Reading Sex and Gender in the Secret Revelation of John

    OpenAIRE

    King, Karen L.

    2011-01-01

    The Secret Revelation of John is replete with imagery of the divine Mother alongside the Father God and his Son Christ. It boasts of powerful female saviors—and even identifies Christ among them. Eve is not the cause of humankind’s fall, but of its redemption. The sexual intercourse of Adam and Eve marks not original sin, but a step toward salvation. Yet readers find, too,an idealized divine world in the pattern of the ancient patriarchal household,and a portrait of another female figure, Sop...

  14. DNA Methylation in Thyroid Tumorigenesis

    International Nuclear Information System (INIS)

    Thyroid cancer is the most common endocrine cancer with 1,690 deaths each year. There are four main types of which the papillary and follicular types together account for >90% followed by medullary cancers with 3% to 5% and anaplastic carcinomas making up <3%. Epigenetic events of DNA hypermethylation are emerging as promising molecular targets for cancer detection. Our immediate and long term goal is to identify DNA methylation markers for early detection of thyroid cancer. This pilot study comprised of 21 patients to include 11 papillary thyroid cancers (PTC), 2 follicular thyroid cancers (FTC), 5 normal thyroid cases, and 3 hyperthyroid cases. Aberrant promoter methylation was examined in 24 tumor suppressor genes using the methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) assay and in the NIS gene using methylation-specific PCR (MSP). The frequently methylated genes were CASP8 (17/21), RASSF1 (16/21) and NIS (9/21). In the normal samples, CASP8, RASSF1 and NIS were methylated in 5/5, 4/5 and 1/5 respectively. In the hyperthyroid samples, CASP8, RASSF1 and NIS were methylated in 3/3, 2/3 and 1/3 respectively. In the thyroid cancers, CASP8, RASSF1, and NIS were methylated in 9/13, 10/13, and 7/13 respectively. CASP8, RASSF1 and NIS were also methylated in concurrently present normal thyroid tissue in 3/11, 4/11 and 3/11 matched thyroid cancer cases (matched for presence of both normal thyroid tissue and thyroid cancer), respectively. Our data suggests that aberrant methylation of CASP8, RASSF1, and NIS maybe an early change in thyroid tumorigenesis regardless of cell type

  15. The REVEL Project: an Oceanographic Research Immersion Professional Development Program

    Science.gov (United States)

    Robigou, V.

    2004-12-01

    The REVEL Project (Research and Education: Volcanoes, Exploration and Life) is an NSF-funded, professional development program for middle and high school science teachers that are motivated to use deep-sea research and seafloor exploration as tools to implement inquiry-based science in their classrooms, schools, and districts, and to share their experiences with their communities. Initiated in 1996 as a regional program for Northwest science educators, REVEL evolved into a multi-institutional program inviting teachers to practice doing research on sea-going research expeditions. Today the project offers teachers throughout the U. S. an opportunity to participate and contribute to international, multidisciplinary, deep-sea research in the Northeast Pacific ocean to study the relationship between geological processes such as earthquakes and volcanism, fluid circulation and life on our planet. In addition, the program supports teachers to implement research-based, data-oriented activities in their classrooms, and prepares them to use curriculum that will enhance student learning through the research process. Evaluation for year 2003-2004 of the program reveals that the program is designed as a successful research immersion opportunity during which teachers learn content, process, culture and ethos of authentic research. Qualitative results indicate that teachers who have participated in the program assimilate the scientific process over several years and share their expertise in ways most beneficial for their communities for years to come.

  16. Judging Transitional Justice: A New Criterion for Evaluating Truth Revelation Procedures

    Science.gov (United States)

    Kaminski, Marek M.; Nalepa, Monika

    2006-01-01

    Truth revelation procedures are evaluated according to various normative criteria. The authors find the concepts of false conviction and false acquittal more adequate for such evaluation than the conformity with the rule of law and apply a useful classification of truth revelation procedures into incentive-based (ITRs) and evidence-based ones…

  17. Amping up estrogen receptors in breast cancer

    OpenAIRE

    Fowler, Amy M; Alarid, Elaine T

    2007-01-01

    This article highlights a recent study by Holst et al. in Nature Genetics that finds estrogen receptor-alpha (ER-α) amplification in early benign lesions and more advanced invasive carcinomas of the breast, and discusses the potential implications to our present understanding of the role of ER-α in breast tumorigenesis.

  18. Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Dipankar Ray

    2011-05-01

    Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

  19. FAK overexpression and p53 mutations are highly correlated in human breast cancer

    OpenAIRE

    Golubovskaya, Vita M; Conway, Kathleen; Edmiston, Sharon N; Tse, Chiu-Kit; Lark, Amy L.; Livasy, Chad A.; Moore, Dominic; Millikan, Robert C.; Cance, William G

    2009-01-01

    Focal Adhesion Kinase (FAK) is overexpressed in a number of tumors, including breast cancer. Another marker of breast cancer tumorigenesis is the tumor suppressor gene p53 that is frequently mutated in breast cancer. In the present study, our aim was to find a correlation between FAK overexpression, p53 expression and mutation status in a population-based series of invasive breast cancer tumors from the Carolina Breast Cancer Study. Immunohistochemical analyses of 622 breast cancer tumors rev...

  20. Genetic mechanisms in Apc-mediated mammary tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Mari Kuraguchi

    2009-02-01

    Full Text Available Many components of Wnt/beta-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively. Only the K14-cre-mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of beta-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; Apc(CKO/+ mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre-induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre-mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands. Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of beta-catenin signaling optimal for mammary tumor development and explain partially the colon- but not mammary-specific tumor development in patients that carry germline mutations in APC.

  1. Revel v izobrazhenii russkihh pissatelei i hudozhnikov 1820-1840-hh gg / Sergei Issakov

    Index Scriptorium Estoniae

    Issakov, Sergei, 1931-2013

    2006-01-01

    Aleksandr Bestuzhev-Marlinski reisikirjast "Pojezdka v Revel" (1921) ja tema nn. liivimaa jutustustest, eriti "Reveli turniirist" (1824) alguse saanud Tallinna kujutamise traditsioon vene kirjanduses a-tel 1820-1840

  2. Prepubertal exposure to cow’s milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    OpenAIRE

    Nielsen, Tina S.; Khan, Galam; Davis, Jennifer; Michels, Karin B; Hilakivi-Clarke, Leena

    2011-01-01

    Cow’s milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague Dawley rats were given either whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene (DMBA) on P...

  3. The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis

    Science.gov (United States)

    Su, Jiaming; Wang, Fei; Cai, Yong; Jin, Jingji

    2016-01-01

    Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first) is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs). As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL) in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16); however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8), suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways. PMID:26784169

  4. The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Jiaming Su

    2016-01-01

    Full Text Available Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60 family of histone acetyltransferases (HATs. As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16; however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8, suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways.

  5. The acetyltransferase Tip60 contributes to mammary tumorigenesis by modulating DNA repair.

    Science.gov (United States)

    Bassi, C; Li, Y-T; Khu, K; Mateo, F; Baniasadi, P S; Elia, A; Mason, J; Stambolic, V; Pujana, M A; Mak, T W; Gorrini, C

    2016-07-01

    The acetyltransferase Tip60/Kat5 acetylates both histone and non-histone proteins, and is involved in a variety of biological processes. By acetylating p53, Tip60 controls p53-dependent transcriptional activity and so is implicated as a tumor suppressor. However, many breast cancers with low Tip60 also show p53 mutation, implying that Tip60 has a tumor suppressor function independent of its acetylation of p53. Here, we show in a p53-null mouse model of sporadic invasive breast adenocarcinoma that heterozygosity for Tip60 deletion promotes mammary tumorigenesis. Low Tip60 reduces DNA repair in normal and tumor mammary epithelial cells, both under resting conditions and following genotoxic stress. We demonstrate that Tip60 controls homologous recombination (HR)-directed DNA repair, and that Tip60 levels correlate inversely with a gene expression signature associated with defective HR-directed DNA repair. In human breast cancer data sets, Tip60 mRNA is downregulated, with low Tip60 levels correlating with p53 mutations in basal-like breast cancers. Our findings indicate that Tip60 is a novel breast tumor suppressor gene whose loss results in genomic instability leading to cancer formation. PMID:26915295

  6. NF-kappaB in Lung Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Zhenjian [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

    2011-12-14

    The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis.

  7. The role of menin in parathyroid tumorigenesis.

    LENUS (Irish Health Repository)

    Davenport, Colin

    2009-01-01

    Primary hyperparathyroidism is a common disorder that involves the pathological enlargement of one or more parathyroid glands resulting in excessive production of parathyroid hormone (PTH). The exact pathogenesis of this disease remains to be fully understood. In recent years interest has focussed on the interaction between menin protein and the transforming growth factor (TGF)-beta\\/Smad signalling pathway. In vitro experimentation has demonstrated that the presence of menin is required for TGF-beta to effectively inhibit parathyroid cell proliferation and PTH production. This observation correlates with the almost universal occurrence of parathyroid tumors accompanying the inactivation of menin in multiple endocrine neoplasia Type 1 (MEN1) syndrome and the high rate of somatic menin gene mutations seen in sporadic parathyroid adenomas. This chapter aims to review the role of menin in primary hyperparathyroidism and parathyroid hormone-regulation, including the influences of MEN1 gene mutations on parathyroid cell proliferation, differentiation and tumorigenesis.

  8. Rho GTPases of the RhoBTB subfamily and tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Jessica BERTHOLD; Kristína SCHENKOV(A); Francisco RIVERO

    2008-01-01

    RhoBTB proteins constitute a subfamily of atypical members within the Rho fami-ly of small guanosine triphosphatases (GTPases).Their most salient feature is their domain architecture:a GTPase domain (in most cases,non-functional) is followed by a proline-rich region,a tandem of 2 broad-complex,tramtrack,bric hrac (BTB) domains,and a conserved C-terminal region.In humans,the RhoBTB subfamily consists of 3 isoforms:RhoBTB 1,RhoBTB2,and RhoBTB3.Orthologs are present in several other eukaryotes,such as Drosophila and Dictyostelium,but have been lost in plants and fungi.Interest in RhoBTB arose when RHOBTB2 was identified as the gene homozygously deleted in breast cancer samples and was proposed as a candidate tumor suppressor gene,a property that has been extended to RHOBTBI.The functions of RhoBTB proteins have not been defined yet,but may be related to the roles of BTB domains in the recruitment of cullin3,a component of a family of uhiquitin ligases.A model emerges in which RhoBTB proteins are required to maintain constant levels of putative substrates involved in cell cycle regulation or vesicle transport through targeting for degradation in the 26S proteasome.RhoBTB proteins are engrossing the list of Rho GTPases involved in tumorigenesis.Unlike typical Rho GTPases (usually overexpressed or hyperactive),RhoBTB proteins appear to play a part in the carcinogenic process through a mechanism that involves the decreased or abolished expression of the corresponding genes,or more rarely,mutations that result in impaired functioning of the protein,presumably leading to the accumulation of RhoBTB substrates and alterations of the cellular homeostasis.

  9. Revelation, Redemption, and World Religions: A Pentecostal Perspective on the Inclusive Embrace of Divine Providence

    Science.gov (United States)

    Richie, Tony

    2009-01-01

    This article addresses the development of a Christian theology of religions well equipped for engagement with religious others through discussion of the nature of religion, revelation, and redemption. It affirms the extensiveness of providence from an inclusive perspective and argues that Pentecostal pneumatology contributes positively to…

  10. Dietary compound isoliquiritigenin prevents mammary carcinogenesis by inhibiting breast cancer stem cells through WIF1 demethylation

    OpenAIRE

    Wang, Neng; Wang, Zhiyu; Wang, Yu; Xie, Xiaoming; Shen, Jiangang; Peng, Cheng; You, Jieshu; Peng, Fu; Tang, Hailin; Guan, Xinyuan; Chen, Jianping

    2015-01-01

    Breast cancer stem cells (CSCs) are considered as the root of mammary tumorigenesis. Previous studies have demonstrated that ISL efficiently limited the activities of breast CSCs. However, the cancer prevention activities of ISL and its precise molecular mechanisms remain largely unknown. Here, we report a novel function of ISL as a natural demethylation agent targeting WIF1 to prevent breast cancer. ISL administration suppressed in vivo breast cancer initiation and progression, accompanied b...

  11. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Jianxin Lu; Lokendra Kumar Sharma; Yidong Bai

    2009-01-01

    Alterations in oxidative phosphorylation resulting from mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA (mtDNA) mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed.

  12. PKA signaling drives mammary tumorigenesis through Src.

    Science.gov (United States)

    Beristain, A G; Molyneux, S D; Joshi, P A; Pomroy, N C; Di Grappa, M A; Chang, M C; Kirschner, L S; Privé, G G; Pujana, M A; Khokha, R

    2015-02-26

    Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias; however, its role in sporadic epithelial cancers is unknown. Here, we show that heightened PKA activity in the mammary epithelium generates tumors. Mammary-restricted biallelic ablation of Prkar1a, which encodes for the critical type-I PKA regulatory subunit, induced spontaneous breast tumors characterized by enhanced type-II PKA activity. Downstream of this, Src phosphorylation occurs at residues serine-17 and tyrosine-416 and mammary cell transformation is driven through a mechanism involving Src signaling. The phenotypic consequences of these alterations consisted of increased cell proliferation and, accordingly, expansion of both luminal and basal epithelial cell populations. In human breast cancer, low PRKAR1A/high SRC expression defines basal-like and HER2 breast tumors associated with poor clinical outcome. Together, the results of this study define a novel molecular mechanism altered in breast carcinogenesis and highlight the potential strategy of inhibiting SRC signaling in treating this cancer subtype in humans. PMID:24662820

  13. Wnt/β-catenin signaling regulated SATB1 promotes colorectal cancer tumorigenesis and progression.

    Science.gov (United States)

    Mir, R; Pradhan, S J; Patil, P; Mulherkar, R; Galande, S

    2016-03-31

    The chromatin organizer SATB1 has been implicated in the development and progression of multiple cancers including breast and colorectal cancers. However, the regulation and role of SATB1 in colorectal cancers is poorly understood. Here, we demonstrate that expression of SATB1 is induced upon hyperactivation of Wnt/β-catenin signaling and repressed upon depletion of TCF7L2 (TCF4) and β-catenin. Using several colorectal cancer cell line models and the APC min mutant zebrafish in vivo model, we established that SATB1 is a novel target of Wnt/β-catenin signaling. We show that direct binding of TCF7L2/β-catenin complex on Satb1 promoter is required for the regulation of SATB1. Moreover, SATB1 is sufficient to regulate the expression of β-catenin, members of TCF family, multiple downstream effectors and mediators of Wnt pathway. SATB1 potentiates the cellular changes and expression of key cancer-associated genes in non-aggressive colorectal cells, promotes their aggressive phenotype and tumorigenesis in vivo. Conversely, depletion of SATB1 from aggressive cells reprograms the expression of cancer-associated genes, reverses their cancer phenotype and reduces the potential of these cells to develop tumors in vivo. We also show that SATB1 and β-catenin bind to the promoters of TCF7L2 and the downstream targets of Wnt signaling and regulate their expression. Our findings suggest that SATB1 shares a feedback regulatory network with TCF7L2/β-catenin signaling and is required for Wnt signaling-dependent regulation of β-catenin. Collectively, these results provide unequivocal evidence to establish that SATB1 reprograms the expression of tumor growth- and metastasis-associated genes to promote tumorigenesis and functionally overlaps with Wnt signaling critical for colorectal cancer tumorigenesis. PMID:26165840

  14. Fbxw7 Tumor Suppressor: A Vital Regulator Contributes to Human Tumorigenesis.

    Science.gov (United States)

    Cao, Jun; Ge, Ming-Hua; Ling, Zhi-Qiang

    2016-02-01

    Rapidly accumulating data indicate that F-box/WD repeat-containing protein 7 (Fbxw7) is one of the most frequently mutated genes in human cancers and regulates a network of crucial oncoproteins. These studies have generated important new insights into tumorigenesis and may soon enable therapies targeting the Fbxw7 pathway. We searched PubMed, Embase, and ISI Web of Science databases (1973-2015, especially recent 5 years) for articles published in the English language using the key words "Fbxw7," "Fbw7," "hCDC4," and "Sel-10," and we reviewed recent developments in the search for Fbxw7. Fbxw7 coordinates the ubiquitin-dependent proteolysis of several critical cellular regulators, thereby controlling essential processes, such as cell cycle, differentiation, and apoptosis. Fbxw7 contains 3 isoforms (Fbxw7α, Fbxw7β, and Fbxw7γ), and they are differently regulated in subtract recognition. Besides those, Fbxw7 activity is controlled at different levels, resulting in specific and tunable regulation of the abundance and activity of its substrates in a variety of human solid tumor types, including glioma malignancy, nasopharyngeal carcinoma, osteosarcoma, melanoma as well as colorectal, lung, breast, gastric, liver, pancreatic, renal, prostate, endometrial, and esophageal cancers. Fbxw7 is strongly associated with tumorigenesis, and the mechanisms and consequences of Fbxw7 deregulation in cancers may soon enable the development of novel therapeutic approaches. PMID:26886596

  15. Maternal exercise during pregnancy reduces risk of mammary tumorigenesis in rat offspring.

    Science.gov (United States)

    Camarillo, Ignacio G; Clah, Leon; Zheng, Wei; Zhou, Xuanzhu; Larrick, Brienna; Blaize, Nicole; Breslin, Emily; Patel, Neal; Johnson, Diamond; Teegarden, Dorothy; Donkin, Shawn S; Gavin, Timothy P; Newcomer, Sean

    2014-11-01

    Breast cancer is the most common cancer among women. Emerging research indicates that modifying lifestyle factors during pregnancy may convey long-term health benefits to offspring. This study was designed to determine whether maternal exercise during pregnancy leads to reduced mammary tumorigenesis in female offspring. Pregnant rats were randomly assigned to exercised and sedentary groups, with the exercised group having free access to a running wheel and the sedentary group housed with a locked wheel during pregnancy. Female pups from exercised or sedentary dams were weaned at 21 days of age and fed a high fat diet without access to a running wheel. At 6 weeks, all pups were injected with the carcinogen N-methyl-N-nitrosourea. Mammary tumor development in all pups was monitored for 15 weeks. Pups from exercised dams had a substantially lower tumor incidence (42.9%) compared with pups from sedentary dams (100%). Neither tumor latency nor histological grade differed between the two groups. These data are the first to demonstrate that exercise during pregnancy potentiates reduced tumorigenesis in offspring. This study provides an important foundation towards developing more effective modes of behavior modification for cancer prevention. PMID:24950432

  16. Maternal Exercise During Pregnancy Reduces Risk of Mammary Tumorigenesis In Rat Offspring

    Science.gov (United States)

    Camarillo, Ignacio; Clah, Leon; Zheng, Wei; Zhou, Xuanzhu; Larrick, Brienna; Blaize, Nicole; Breslin, Emily; Patel, Neal; Johnson, Diamond; Teegarden, Dorothy; Donkin, Shawn S.; Gavin, Timothy P.; Newcomer, Sean

    2015-01-01

    Breast cancer is the most common cancer among women. Emerging research indicates that modifying lifestyle factors during pregnancy may convey long-term health benefits to offspring. This study was designed to determine whether maternal exercise during pregnancy leads to reduced mammary tumorigenesis in female offspring. Pregnant rats were randomly assigned to exercised and sedentary groups, with the exercised group having free access to a running wheel and the sedentary group housed with a locked wheel during pregnancy. Female pups from exercised or sedentary dams were weaned at 21 days of age and fed a high fat diet without access to a running wheel. At 6 weeks, all pups were injected with the carcinogen N-methyl-N-nitrosourea (MNU). Mammary tumor development in all pups was monitored for 15 weeks. Pups from exercised dams had a substantially lower tumor incidence (42.9%) compared to pups from sedentary dams (100%). Neither tumor latency nor histological grade differed between the two groups. These data are the first to demonstrate that exercise during pregnancy potentiates reduced tumorigenesis in offspring. This study provides an important foundation towards developing more effective modes of behavior modification for cancer prevention. PMID:24950432

  17. miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion.

    Directory of Open Access Journals (Sweden)

    Dahu Chen

    2014-02-01

    Full Text Available Whether epithelial-mesenchymal transition (EMT is always linked to increased tumorigenicity is controversial. Through microRNA (miRNA expression profiling of mammary epithelial cells overexpressing Twist, Snail or ZEB1, we identified miR-100 as a novel EMT inducer. Surprisingly, miR-100 inhibits the tumorigenicity, motility and invasiveness of mammary tumor cells, and is commonly downregulated in human breast cancer due to hypermethylation of its host gene MIR100HG. The EMT-inducing and tumor-suppressing effects of miR-100 are mediated by distinct targets. While miR-100 downregulates E-cadherin by targeting SMARCA5, a regulator of CDH1 promoter methylation, this miRNA suppresses tumorigenesis, cell movement and invasion in vitro and in vivo through direct targeting of HOXA1, a gene that is both oncogenic and pro-invasive, leading to repression of multiple HOXA1 downstream targets involved in oncogenesis and invasiveness. These findings provide a proof-of-principle that EMT and tumorigenicity are not always associated and that certain EMT inducers can inhibit tumorigenesis, migration and invasion.

  18. Overexpression of Human Cripto-1 in Transgenic Mice Delays Mammary Gland Development and Differentiation and Induces Mammary Tumorigenesis

    OpenAIRE

    Sun, Youping; Strizzi, Luigi; Raafat, Ahmed; Hirota, Morihisa; Bianco, Caterina; Feigenbaum, Lionel; Kenney, Nicholas; Wechselberger, Christian; Callahan, Robert; Salomon, David S.

    2005-01-01

    Overexpression of Cripto-1 has been reported in several types of human cancers including breast cancer. To investigate the role of human Cripto-1 (CR-1) in mammary gland development and tumorigenesis, we developed transgenic mice that express the human CR-1 transgene under the regulation of the whey acidic protein (WAP) promoter in the FVB/N mouse background. The CR-1 transgene was detected in the mammary gland of 15-week-old virgin WAP-CR-1 female mice that eventually developed hyperplastic ...

  19. Prepubertal exposure to cow's milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Khan, Galam; Davis, Jennifer;

    2011-01-01

    Cow's milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague-Dawley rats were given either...... whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene on PND 50. Milk exposure increased circulating E2 levels on PND 25 by 10-fold (p < 0.001) and accelerated vaginal...... opening, which marks puberty onset, by 2.5 days (p < 0.001). However, rats exposed to milk before puberty exhibited reduced carcinogen-induced mammary carcinogenesis; that is, their tumor latency was longer (p < 0.03) and incidence was lower (p < 0.05) than in the controls. On PND 25 and 50, mammary...

  20. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

    DEFF Research Database (Denmark)

    Purrington, Kristen S; Slettedahl, Seth; Bolla, Manjeet K;

    2014-01-01

    Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymor...

  1. Breast lift

    Science.gov (United States)

    Mastopexy; Breast lift with reduction; Breast lift with augmentation ... enlargement with implants) when they have a breast lift. ... it for medical reasons. Women usually have breast lifts to lift sagging, loose breasts. Pregnancy, breastfeeding, and ...

  2. Developmental context determines latency of MYC-induced tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Shelly Beer

    2004-11-01

    Full Text Available One of the enigmas in tumor biology is that different types of cancers are prevalent in different age groups. One possible explanation is that the ability of a specific oncogene to cause tumorigenesis in a particular cell type depends on epigenetic parameters such as the developmental context. To address this hypothesis, we have used the tetracycline regulatory system to generate transgenic mice in which the expression of a c-MYC human transgene can be conditionally regulated in murine hepatocytes. MYC's ability to induce tumorigenesis was dependent upon developmental context. In embryonic and neonatal mice, MYC overexpression in the liver induced marked cell proliferation and immediate onset of neoplasia. In contrast, in adult mice MYC overexpression induced cell growth and DNA replication without mitotic cell division, and mice succumbed to neoplasia only after a prolonged latency. In adult hepatocytes, MYC activation failed to induce cell division, which was at least in part mediated through the activation of p53. Surprisingly, apoptosis is not a barrier to MYC inducing tumorigenesis. The ability of oncogenes to induce tumorigenesis may be generally restrained by developmentally specific mechanisms. Adult somatic cells have evolved mechanisms to prevent individual oncogenes from initiating cellular growth, DNA replication, and mitotic cellular division alone, thereby preventing any single genetic event from inducing tumorigenesis.

  3. Aberrant promoter CpG methylation and its translational applications in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ting-Xiu Xiang; Ying Yuan; Li-Li Li; Zhao-Hui Wang; Liang-Ying Dan; Yan Chen; Guo-Sheng Ren; Qian Tao

    2013-01-01

    Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes (TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.

  4. Role of JNK in mammary gland development and breast cancer

    OpenAIRE

    Cellurale, Cristina; Girnius, Nomeda; Jiang, Feng; Cavanagh-Kyros, Julie; Lu, Shaolei; Garlick, David S.; Mercurio, Arthur M.; Davis, Roger J

    2011-01-01

    JNK signaling has been implicated in the developmental morphogenesis of epithelial organs. In this study we employed a compound deletion of the murine Jnk1 and Jnk2 genes in the mammary gland to evaluate the requirement for these ubiquitously expressed genes in breast development and tumorigenesis. JNK1/2 was not required for breast epithelial cell proliferation or motility. However, JNK1/2 deficiency caused increased branching morphogenesis and defects in the clearance of lumenal epithelial ...

  5. A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

    International Nuclear Information System (INIS)

    Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Using the first transgenic animal model to

  6. Hypoxic conditions induce a cancer-like phenotype in human breast epithelial cells

    DEFF Research Database (Denmark)

    Vaapil, Marica; Helczynska, Karolina; Villadsen, René;

    2012-01-01

    Solid tumors are less oxygenated than their tissue of origin. Low intra-tumor oxygen levels are associated with worse outcome, increased metastatic potential and immature phenotype in breast cancer. We have reported that tumor hypoxia correlates to low differentiation status in breast cancer. Less...... is known about effects of hypoxia on non-malignant cells. Here we address whether hypoxia influences the differentiation stage of non-malignant breast epithelial cells and potentially have bearing on early stages of tumorigenesis....

  7. IGFBP3 mRNA expression in benign and malignant breast tumors

    OpenAIRE

    Ren, Zefang; Shin, Aesun; Cai, Qiuyin; Shu, Xiao-Ou; Gao, Yu-Tang; Zheng, Wei

    2007-01-01

    Introduction Most previous studies have focused on evaluating the association between circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels and breast cancer risk. Emerging evidence over the past few years suggests that IGFBP-3 may act directly on mammary epithelial cells. Methods To understand the role of IGFBP-3 in breast tumorigenesis, we investigated IGFBP3 mRNA expression levels in benign and malignant breast tumors and their adjacent normal tissues using real-time qu...

  8. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility

    DEFF Research Database (Denmark)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B;

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and.......5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry....

  9. Aberrantly methylated DNA as a biomarker in breast cancer

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Jørgensen, Lars Mønster; Guldberg, Per;

    2013-01-01

    hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients......Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA...... occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients into...

  10. Gpr177 deficiency impairs mammary development and prohibits Wnt-induced tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Eri Ohfuchi Maruyama

    Full Text Available Aberrant regulation of the Wnt pathway, essential for various developmental processes, is tightly linked to human breast cancers. By hijacking this evolutionary conserved signaling pathway, cancer cells acquire sustaining proliferation ability, leading to modification of physiologic properties necessary for tumor initiation and progression. An enormous wealth of knowledge on the importance of Wnt signaling in breast development and cancer has been obtained, but the cell types responsible for production of this proliferative signal operating within normal and malignant tissues remains poorly understood. Here we report that Wnt production mediated by Gpr177 is essential for mammary morphogenesis. The loss of Gpr177 interferes with mammary stem cells, leading to deficiencies in cell proliferation and differentiation. Genetic analysis further demonstrates an indispensable role of Gpr177 in Wnt-induced tumorigenesis. The Gpr177-deficiency mice are resistant to malignant transformation. This study not only demonstrates the necessity of Wnt in mammary organogenesis but also provides a proof-of-principle for targeting of Gpr177 as a potential new treatment for human diseases with aberrant Wnt stimulation.

  11. EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 李柏林; 宋敏; 宋继谒

    2004-01-01

    Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

  12. Noncoding RNAs in breast cancer.

    Science.gov (United States)

    Lo, Pang-Kuo; Wolfson, Benjamin; Zhou, Xipeng; Duru, Nadire; Gernapudi, Ramkishore; Zhou, Qun

    2016-05-01

    The mammalian transcriptome has recently been revealed to encompass a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. MicroRNAs (miRNAs), the best studied of the short noncoding RNAs (sncRNAs), have been extensively characterized with regard to their biogenesis, function and importance in tumorigenesis. Another class of sncRNAs called piwi-interacting RNAs (piRNAs) has also gained attention recently in cancer research owing to their critical role in stem cell regulation. Long noncoding RNAs (lncRNAs) of >200 nucleotides in length have recently emerged as key regulators of developmental processes, including mammary gland development. lncRNA dysregulation has also been implicated in the development of various cancers, including breast cancer. In this review, we describe and discuss the roles of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the initiation and progression of breast tumorigenesis, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor ncRNAs. Moreover, the current and potential future applications of ncRNAs to clinical breast cancer research are also discussed, with an emphasis on ncRNA-based diagnosis, prognosis and future therapeutics. PMID:26685283

  13. A critical reassessment of the role of mitochondria in tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Antonio Salas

    2005-11-01

    Full Text Available BACKGROUND: Mitochondrial DNA (mtDNA is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results. METHODS AND FINDINGS: In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis. CONCLUSION: The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research.

  14. Mammary tumorigenesis by radiation and its prevention

    Energy Technology Data Exchange (ETDEWEB)

    Onoda, Makoto; Suzuki, Keiko; Inano, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-06-01

    Since the breast cancer in women emerged as an important risk associated with exposure to ionizing radiation, we have investigated to clarify the relationship between the induction of mammary tumors by irradiation and the developmental stage of the mammary glands that regulated by the action of endocrine hormones. Besides the radiation, epidemiological studies showed that the process of biosynthesis/metabolism of steroid hormones and hyperlipidemia may be associated with an increased risk of mammary carcinogenesis. In this context, we have undertaken investigations to evaluate the anti-carcinogenic activities of dehydroepiandrosterone (DHEA), a major secretory steroid of the adrenal glands, bezafibrate (BEZF), an anti-hyperlipidemic drug derived from clofibrate, and simvastatin (SIMV), a prodrug of a specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, against diethylstilbestrol (DES)-dependent promotion/progression of rat mammary tumors initiated by {gamma}-rays. Pregnant Wistar-MS rats received whole-body irradiation with 2.6 Gy of {gamma}-rays from a {sup 60}Co source at day-20 of pregnancy. The mother rats were fed a diet containing either 0.6% DHEA, 0.15% BEZF or 0.03% SIMV beginning immediately after weaning. They were then implanted subcutaneously with a pellet of DES (3 mg/pellet) in the interscapular area 30 days after termination of nursing and were observed for 1 year for detection of palpable mammary tumors starting from the time of pellet implantation. The administration of dietary DHEA, BEZF or SIMV together with DES implantation in rats irradiated in late pregnancy significantly decreased the total incidence of mammary tumors to 35%, 27% and 36%, respectively, for the 1 year period, while higher tumor incidence (96%, 90% and 88%) was observed in rats fed controldiet. However, neither the number of mammary tumors per tumor-bearing rat nor the latency period in the drug treated groups was different from that observed in the control group

  15. Mammary tumorigenesis by radiation and its prevention

    International Nuclear Information System (INIS)

    Since the breast cancer in women emerged as an important risk associated with exposure to ionizing radiation, we have investigated to clarify the relationship between the induction of mammary tumors by irradiation and the developmental stage of the mammary glands that regulated by the action of endocrine hormones. Besides the radiation, epidemiological studies showed that the process of biosynthesis/metabolism of steroid hormones and hyperlipidemia may be associated with an increased risk of mammary carcinogenesis. In this context, we have undertaken investigations to evaluate the anti-carcinogenic activities of dehydroepiandrosterone (DHEA), a major secretory steroid of the adrenal glands, bezafibrate (BEZF), an anti-hyperlipidemic drug derived from clofibrate, and simvastatin (SIMV), a prodrug of a specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, against diethylstilbestrol (DES)-dependent promotion/progression of rat mammary tumors initiated by γ-rays. Pregnant Wistar-MS rats received whole-body irradiation with 2.6 Gy of γ-rays from a 60Co source at day-20 of pregnancy. The mother rats were fed a diet containing either 0.6% DHEA, 0.15% BEZF or 0.03% SIMV beginning immediately after weaning. They were then implanted subcutaneously with a pellet of DES (3 mg/pellet) in the interscapular area 30 days after termination of nursing and were observed for 1 year for detection of palpable mammary tumors starting from the time of pellet implantation. The administration of dietary DHEA, BEZF or SIMV together with DES implantation in rats irradiated in late pregnancy significantly decreased the total incidence of mammary tumors to 35%, 27% and 36%, respectively, for the 1 year period, while higher tumor incidence (96%, 90% and 88%) was observed in rats fed controldiet. However, neither the number of mammary tumors per tumor-bearing rat nor the latency period in the drug treated groups was different from that observed in the control group. From histological

  16. Statistics Revelations

    Science.gov (United States)

    Chicot, Katie; Holmes, Hilary

    2012-01-01

    The use, and misuse, of statistics is commonplace, yet in the printed format data representations can be either over simplified, supposedly for impact, or so complex as to lead to boredom, supposedly for completeness and accuracy. In this article the link to the video clip shows how dynamic visual representations can enliven and enhance the…

  17. Revelations of a modern mystic:the life and legacy of Kun bzang bde chen gling pa 1928-2006

    OpenAIRE

    Hall, Amelia J.E.; Ramble, C; Roesler, U.

    2012-01-01

    This study traces the development of Tibetan ‘treasure’ texts and practices in contemporary times via the life-story and scriptural revelations of the Tibetan ‘treasure revealer’ (gter ston) Kun bzang bde chen gling pa (1928-2006). It examines how his revelations (gter ma) rooted in the historic spirituality of Tibet, continue and adapt into the twenty first century. The study is important in order to understand the ways this Asian religious concept develops and coalesces in North America....

  18. The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis

    Directory of Open Access Journals (Sweden)

    Thames Howard D

    2008-09-01

    -expressing cells of the murine mammary gland results in the development of squamous metaplastic lesions in nulliparous females, and in mammary tumors in biparous mice, suggesting that ATF3 acts as a mammary oncogene. A subset of human breast tumors expresses high levels of ATF3, suggesting that ATF3 may play an oncogenic role in human breast tumorigenesis, and therefore may be useful as either a biomarker or therapeutic target.

  19. The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis

    International Nuclear Information System (INIS)

    development of squamous metaplastic lesions in nulliparous females, and in mammary tumors in biparous mice, suggesting that ATF3 acts as a mammary oncogene. A subset of human breast tumors expresses high levels of ATF3, suggesting that ATF3 may play an oncogenic role in human breast tumorigenesis, and therefore may be useful as either a biomarker or therapeutic target

  20. What Is Breast Cancer?

    Science.gov (United States)

    ... Next Topic Types of breast cancers What is breast cancer? Breast cancer starts when cells in the breast ... breast cancer? ” and Non-cancerous Breast Conditions . How Breast Cancer Spreads Breast cancer can spread through the lymph ...

  1. Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer

    OpenAIRE

    Rhodes, Lyndsay V.; Tilghman, Syreeta L.; Boue, Stephen M.; Wang, Shuchun; KHALILI, HAFEZ; Muir, Shannon E.; Bratton, Melyssa R.; Zhang, Qiang; Wang, Guangdi; BUROW, MATTHEW E.; Collins-Burow, Bridgette M.

    2011-01-01

    The purpose of this study was to investigate the effects of glyceollins on the suppression of tumorigenesis in triple-negative breast carcinoma cell lines. We further explored the effects of glyceollins on microRNA and protein expression in MDA-MB-231 cells. Triple-negative (ER-, PgR- and Her2/neu-) breast carcinoma cells were used to test the effects of glyceollins on tumorigenesis in vivo. Following this procedure, unbiased microarray analysis of microRNA expression was performed. Additiona...

  2. Low doses of arsenic, via perturbing p53, promotes tumorigenesis.

    Science.gov (United States)

    Ganapathy, Suthakar; Li, Ping; Fagman, Johan; Yu, Tianqi; Lafontant, Jean; Zhang, Guojun; Chen, Changyan

    2016-09-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure. PMID:27425828

  3. Breast Cancer-derived Dickkopf1 Inhibits Osteoblast Differentiation and Osteoprotegerin Expression: Implication for Breast Cancer Osteolytic Bone Metastases

    OpenAIRE

    Bu, Guojun; Lu, Wenyan; Liu, Chia-Chen; Selander, Katri; Yoneda, Toshiyuki; Hall, Christopher; Evan T. Keller; Li, Yonghe

    2008-01-01

    Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/β-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/β-catenin antagonist. In the present study, we demonstrated that activation of Wnt/β-catenin signaling enhanced Dkk1 expression i...

  4. The role of Notch signaling in development and tumorigenesis

    OpenAIRE

    Mazur, Pawel Karol

    2010-01-01

    This thesis underscores the high importance of Notch signaling in the development of pancreas and liver as well as in tumorigenesis of pancreas and skin. Pancreas-specific ablation of Notch signaling impairs exocrine cell expansion and leads to premature differentiation of progenitor into endocrine cells. In addition, Notch was found to play an essential role in pancreas recovery after acute pancreatitis. Also, Notch is critical for intrahepatic bile duct formation during liver maturation. Fi...

  5. Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis

    OpenAIRE

    Zhai, Zongzhao; Kondo, Shu; Ha, Nati; Boquete, Jean-Philippe; Brunner, Michael; Ueda, Ryu; Lemaitre, Bruno

    2015-01-01

    Stem cell self-renewal and differentiation are coordinated to maintain tissue homeostasis and prevent cancer. Mutations causing stem cell proliferation are traditionally the focus of cancer studies. However, the contribution of the differentiating stem cell progenies in tumorigenesis is poorly characterized. Here we report that loss of the SOX transcription factor, Sox21a, blocks the differentiation programme of enteroblast (EB), the intestinal stem cell progeny in the adult Drosophila midgut...

  6. A critical reassessment of the role of mitochondria in tumorigenesis.

    OpenAIRE

    Antonio Salas; Yong-Gang Yao; Vincent Macaulay; Ana Vega; Angel Carracedo; Hans-Jürgen Bandelt

    2005-01-01

    Background: Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results. Methods and Findings: In ...

  7. Developmental context determines latency of MYC-induced tumorigenesis.

    OpenAIRE

    Shelly Beer; Anders Zetterberg; Ihrie, Rebecca A.; Ryan A McTaggart; Qiwei Yang; Nicole Bradon; Constadina Arvanitis; Attardi, Laura D.; Sandy Feng; Boris Ruebner; Cardiff, Robert D.; Felsher, Dean W.

    2004-01-01

    One of the enigmas in tumor biology is that different types of cancers are prevalent in different age groups. One possible explanation is that the ability of a specific oncogene to cause tumorigenesis in a particular cell type depends on epigenetic parameters such as the developmental context. To address this hypothesis, we have used the tetracycline regulatory system to generate transgenic mice in which the expression of a c-MYC human transgene can be conditionally regulated in murine hepato...

  8. Loss of KLF14 triggers centrosome amplification and tumorigenesis

    OpenAIRE

    Fan, Guangjian; Sun, Lianhui; Shan, Peipei; Zhang, Xianying; Huan, Jinliang; Li, Dali; Wang, Tingting; Wei, Tingting; Zhang, Xiaohong; Gu, Xiaoyang; Yao, Liangfang; Xuan, Yang; Hou, Zhaoyuan; Cui, Yongping; Cao, Liu

    2015-01-01

    Centrosome amplification is frequent in cancer, but the underlying mechanisms remain unclear. Here we report that disruption of the Kruppel-like factor 14 (KLF14) gene in mice causes centrosome amplification, aneuploidy and spontaneous tumorigenesis. Molecularly, KLF14 functions as a transcriptional repressor of Plk4, a polo-like kinase whose overexpression induces centrosome overduplication. Transient knockdown of KLF14 is sufficient to induce Plk4-directed centrosome amplification. Clinical...

  9. The Human Cell Surfaceome of Breast Tumors

    Directory of Open Access Journals (Sweden)

    Júlia Pinheiro Chagas da Cunha

    2013-01-01

    Full Text Available Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors.

  10. Effects of n3 Intake on Plasma Phospholipid Fatty Acids and Sex Hormone Profiles in Postmenopausal Women: Potential for Breast Cancer Risk Reduction

    Science.gov (United States)

    Breast cancer risk is associated with dietary fat intake. Omega-6 fatty acids (n6) promote while omega-3 fatty acids (n3) inhibit tumorigenesis. Increased sex hormone (SH) concentrations are associated with risk of breast cancer. The effects of total fat and n3 on SH and PLFA were assessed in a f...

  11. Breast Cancer

    Science.gov (United States)

    Breast cancer affects one in eight women during their lives. Breast cancer kills more women in the United States than ... cancer. No one knows why some women get breast cancer, but there are a number of risk factors. ...

  12. Revelation of Three Periods of Japan Economic Development on the Economic Development of China

    Directory of Open Access Journals (Sweden)

    Shijie Ma

    2009-02-01

    Full Text Available For the development stage, the actuality of China economy is very similar to the initial stage of 1970s in Japan, so we can use some feasible experiences to solve economic problems by Japan at the beginning of 1970s. The research to the foam economy in the middle and late stage of 1980s in Japan induces the consideration whether China would follow the same old disastrous road of Japan in 1980s. After that, from the long term depression of Japan in 1990s, we should exactly treat the China depression theory which has been occurred. Reviewing the course from the boom at the beginning of 1970s to the formation and break of foam in the middle and late of 1980s and to the long term depression in 1990s of economic development experienced by Japan, we can get some revelations about many aspects such as macro-economic control and financial security.

  13. A Confession as Clear as Mud? Making Sense of Lance Armstrong’s Revelations

    DEFF Research Database (Denmark)

    Gleaves, John; Christiansen, Ask Vest

    2013-01-01

    Researching the world of doping can often feel like work as an undertaker: when business is good, it’s usually bad for someone else. And these past few months have been especially good for business. Confessions from high profile cyclists, including Lance Armstrong and a number of high profile...... Rabobank riders, e.g. Michael Rasmussen, doping scandals in American collegiate sport, a whole cluster of revelations from Australian elite sport and testimonies from the Operacion Puerto trial have added new information about closed doping practices. Moreover, it seems that the complex love......-hate relationship between sporting organizations and their anti-doping programs has pointed towards previously underexplored conflicts of interest. So while the past few months would leave any hungry doctoral student salivating over the wealth of new material, it is important to separate out what has become clearer...

  14. John’s use of Scripture in Revelation 1:7

    Directory of Open Access Journals (Sweden)

    M. J.J Menken

    2007-07-01

    Full Text Available Four questions are asked in this paper: (1 Which are the Old Testament passages from which John quotes in Revelation 1:7? (2 To what extent do the separate quotations and their combination belong to the early Christian tradition used by John? (3 How and where did this combination of quotations come into being? (4 What does John aim at with this com- bination of quotations in this context? John makes use of the combination of God’s eschatological agent as depicted in Daniel 7 and the “pierced one” from Zechariah 12 into one figure, to present the traditional early Christian eschatology, phrased in Old Testament terms, as the basis and the starting point of his book.

  15. Mammary cells with active Wnt signaling resist ErbB2-induced tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Wen Bu

    Full Text Available Aberrant activation of Wnt signaling is frequent in human malignancies. In normal epithelial tissues, including the breast, Wnt signaling is active only in a subset of cells, but it is unknown whether this subset of Wnt signaling-active cells is at increased risk of carcinogenesis. We created transgenic mice (TOP-tva in which the synthetic Wnt-responsive promoter TOP controlled the gene encoding TVA, which confers susceptibility to infection by the retroviral vector RCAS. Thus, only cells in which Wnt signaling is active will express tva and be targeted by RCAS. Surprisingly, we found that RCAS-mediated delivery of cDNA encoding a constitutively activated version of ErbB2 (HER2/Neu into the small number of TVA+ mammary epithelial cells in TOP-tva mice failed to induce tumor, while the same virus readily induced mammary tumors after it was delivered into a comparable number of cells in our previously reported mouse line MMTV-tva, whose tva is broadly expressed in mammary epithelium. Furthermore, we could not even detect any early lesions or infected cells in TOP-tva mice at the time of necropsy. Therefore, we conclude that the Wnt pathway-active cell subset in the normal mammary epithelium does not evolve into tumors following ErbB2 activation-rather, they apparently die due to apoptosis, an anticancer "barrier" that we have reported to be erected in some mammary cells followed ErbB2 activation. In accord with these mouse model data, we found that unlike the basal subtype, ErbB2+ human breast cancers rarely involve aberrant activation of Wnt signaling. This is the first report of a defined sub-population of mammalian cells that is "protected" from tumorigenesis by a potent oncogene, and provides direct in vivo evidence that mammary epithelial cells are not equal in their response to oncogene-initiated transformation.

  16. Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

    International Nuclear Information System (INIS)

    Highlights: • SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). • Knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro. • Overexpression of SAMD9 suppressed proliferation and invasion in A549 cells in vitro. • Depletion of SAMD9 increases tumor formation in vivo. - Abstract: The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression

  17. Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy

    Directory of Open Access Journals (Sweden)

    Kay Andrea

    2009-10-01

    Full Text Available Abstract The mammalian target of rapamycin (mTOR is an intracellular serine/threonine protein kinase positioned at a central point in a variety of cellular signaling cascades. The established involvement of mTOR activity in the cellular processes that contribute to the development and progression of cancer has identified mTOR as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including temsirolimus, everolimus, and ridaforolimus (formerly deforolimus have been developed and assessed for their safety and efficacy in patients with cancer. Temsirolimus is an intravenously administered agent approved by the US Food and Drug Administration (FDA and the European Medicines Agency (EMEA for the treatment of advanced renal cell carcinoma (RCC. Everolimus is an oral agent that has recently obtained US FDA and EMEA approval for the treatment of advanced RCC after failure of treatment with sunitinib or sorafenib. Ridaforolimus is not yet approved for any indication. The use of mTOR inhibitors, either alone or in combination with other anticancer agents, has the potential to provide anticancer activity in numerous tumor types. Cancer types in which these agents are under evaluation include neuroendocrine tumors, breast cancer, leukemia, lymphoma, hepatocellular carcinoma, gastric cancer, pancreatic cancer, sarcoma, endometrial cancer, and non-small-cell lung cancer. The results of ongoing clinical trials with mTOR inhibitors, as single agents and in combination regimens, will better define their activity in cancer.

  18. Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Qing; Yu, Tao; Ren, Yao-Yao; Gong, Ting; Zhong, Dian-Sheng, E-mail: zhongdsyx@126.com

    2014-11-07

    Highlights: • SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). • Knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro. • Overexpression of SAMD9 suppressed proliferation and invasion in A549 cells in vitro. • Depletion of SAMD9 increases tumor formation in vivo. - Abstract: The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression.

  19. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    International Nuclear Information System (INIS)

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  20. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bishayee, Anupam, E-mail: abishayee@auhs.edu [Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755 (United States); Mandal, Animesh [Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272 (United States)

    2014-10-15

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  1. Comparative genomic hybridization detects novel amplifications in fibroadenomas of the breast

    DEFF Research Database (Denmark)

    Ojopi, E P; Rogatto, S R; Caldeira, J R;

    2001-01-01

    Comparative genomic hybridization analysis was performed for identification of chromosomal imbalances in 23 samples of fibroadenomas of the breast. Chromosomal gains rather than losses were a feature of these lesions. Only two cases with a familial and/or previous history of breast lesions had gain...... indicates that gain of these regions can also occur in benign breast lesions. Our findings may provide a basis for conducting further investigations to locate and identify genes associated with proliferation that may be involved in the early steps of tumorigenesis of the breast....

  2. Antisense angiopoietin-1 inhibits tumorigenesis and angiogenesis of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Wang; Kai-Chun Wu; De-Xin Zhang; Dai-Ming Fan

    2006-01-01

    AIM: To investigate the effect of angiopoietin-1 (Ang-1)on biological behaviors in vitro and tumorigenesis and angiogenesis in vitro of human gastric cancer cells.METHODS: Human full-length Ang-1 gene was cloned from human placental tissues by RT-PCR method.Recombinant human Ang-1 antisense eukaryotic expression vector was constructed by directional cloning,and transfected by lipofectin method into human gastric cancer line SGC7901 with high Ang-1 expression level.Inhibition efficiency was confirmed by semi- quantitive PCR and Western blot method. Cell growth curve and cell cycle were observed with MTT assays and flow cytometry, respectively. Nude mice tumorigenicity test was employed to compare in vitro tumorigenesis of cells with Ang-1 suppression. Microvessel density (MVD) of implanted tumor tissues was analyzed by immunohistochemistry for factor Ⅷ staining.RESULTS: Full-length Ang-1 gene was successfully cloned and stable transfectants were established,namely 7Ang1- for antisense, and 7901P for empty vector transfected. 7Ang1- cells showed down-regulated Ang-1 expression, while its in vitro proliferation and cell cycle distribution were not significantly changed.In contrast, xenograft of 7Ang1- cells in nude mice had lower volume and weight than those of 7901P after 30 days' implantation (P<0.01, 293.00±95.54 mg vs. 624.00±77.78 mg) accompanied with less vessel formation with MVD 6.00±1.73 compared to 7901P group 8.44±1.33 (P<0.01).CONCLUSION: Ang-1 may play an important role in tumorigenesis and angiogenesis of gastric cancer, and targeting its expression may be beneficial for the therapy of gastric cancer.

  3. Breast Cancer

    Science.gov (United States)

    ... I found something when I did my breast self-exam. What should I do now? How often should I have mammograms? I have breast cancer. What are my treatment options? How often should I do breast self-exams? I have breast cancer. Is my daughter ...

  4. The clinical significance of tumor infiltrating lymphoctyes in breast cancer: does subtype matter?

    International Nuclear Information System (INIS)

    Tumor infiltrating lymphocytes (TILs) are commonly detected in breast tumors but their bearing on disease outcome is uncertain. The importance of TILs appears to be subtype-specific and varies depending on the histologic characteristics of the tumor. As our understanding of tumorigenesis is increasing the relevance of immunobiology will become apparent

  5. Anticancer and Cancer Prevention Effects of Piperine-Free Piper nigrum Extract on N-nitrosomethylurea-Induced Mammary Tumorigenesis in Rats.

    Science.gov (United States)

    Sriwiriyajan, Somchai; Tedasen, Aman; Lailerd, Narissara; Boonyaphiphat, Pleumjit; Nitiruangjarat, Anupong; Deng, Yan; Graidist, Potchanapond

    2016-01-01

    Piper nigrum (P. nigrum) is commonly used in traditional medicine. This current study aimed to investigate the anticancer and cancer preventive activity of a piperine-free P. nigrum extract (PFPE) against breast cancer cells and N-nitrosomethylurea (NMU)-induced mammary tumorigenesis in rats. The cytotoxic effects and the mechanism of action were investigated in breast cancer cells using the MTT assay and Western blot analysis, respectively. An acute toxicity study was conducted according to the Organization for Economic Co-operation and Development guideline. Female Sprague-Dawley rats with NMU-induced mammary tumors were used in preventive and anticancer studies. The results showed that PFPE inhibited the growth of luminal-like breast cancer cells more so than the basal-like ones by induction of apoptosis. In addition, PFPE exhibited greater selectivity against breast cancer cells than colorectal cancer, lung cancer, and neuroblastoma cells. In an acute toxicity study, a single oral administration of PFPE at a dose of 5,000 mg/kg body weight resulted in no mortality and morbidity during a 14-day observation period. For the cancer preventive study, the incidence of tumor-bearing rats was 10% to 20% in rats treated with PFPE. For the anticancer activity study, the growth rate of tumors in the presence of PFPE-treated groups was much slower when compared with the control and vehicle groups. The extract itself caused no changes to the biochemical and hematologic parameters when compared with the control and vehicle groups. In conclusion, PFPE had a low toxicity and a potent antitumor effect on mammary tumorigenesis in rats. PMID:26511488

  6. Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis.

    Science.gov (United States)

    Clemente-Ruiz, Marta; Murillo-Maldonado, Juan M; Benhra, Najate; Barrio, Lara; Pérez, Lidia; Quiroga, Gonzalo; Nebreda, Angel R; Milán, Marco

    2016-02-01

    Chromosomal instability (CIN) is thought to be a source of mutability in cancer. However, CIN often results in aneuploidy, which compromises cell fitness. Here, we used the dosage compensation mechanism (DCM) of Drosophila to demonstrate that chromosome-wide gene dosage imbalance contributes to the deleterious effects of CIN-induced aneuploidy and its pro-tumorigenic action. We present evidence that resetting of the DCM counterbalances the damaging effects caused by CIN-induced changes in X chromosome number. Importantly, interfering with the DCM suffices to mimic the cellular effects of aneuploidy in terms of reactive oxygen species (ROS) production, JNK-dependent cell death, and tumorigenesis upon apoptosis inhibition. We unveil a role of ROS in JNK activation and a variety of cellular and tissue-wide mechanisms that buffer the deleterious effects of CIN, including DNA-damage repair, activation of the p38 pathway, and cytokine induction to promote compensatory proliferation. Our data reveal the existence of robust compensatory mechanisms that counteract CIN-induced cell death and tumorigenesis. PMID:26859353

  7. New and emerging factors in tumorigenesis: an overview

    International Nuclear Information System (INIS)

    This article provides an overview of the genes and cellular processes that have emerged recently as new key factors in tumorigenesis. We review these in the context of three broad categories. First, genome-scale sequencing studies have revealed a set of frequently mutated genes in cancer. Genes that are mutated in >5% of all cancers across tissue types are discussed, with a highlighted focus on the two most frequently mutated genes, TP53 and PIK3CA. Second, the mechanisms of resistance to targeted therapy are reviewed. These include acquired resistance under targeted therapy selection owing to mutations and amplification of genes in the same or parallel signaling pathways. Importantly, sequencing of primary tumors has revealed that therapy-resistant clones already exist prior to targeted therapy, demonstrating that tumor heterogeneity in primary tumors confers a mechanism for inherent therapy resistance. Third, “metastasis-specific genes”, or rather lack thereof, are discussed. While many genes have been shown to be capable of promoting metastasis in experimental systems, no common genetic alterations have been identified specific to metastatic lesions. Rather, the same gene mutations frequently found in primary tumors are also found prevalent in metastases, suggesting that the genes that drive tumorigenesis may also drive metastasis. In this light, an emerging view of metastatic progression is discussed. Collectively, these recent advances in cancer research have refined our knowledge on cancer etiology and progression but also present challenges that will require innovative new approaches to treat and manage cancer

  8. EXPRESSION AND CLINICAL SIGNIFICANCE OF p73A IN BREAST CARCINOMA TISSUES

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xin; SUN Zhi-jun

    2005-01-01

    Objective: To study the expression and clinical significance of p73( in breast carcinomas. Methods: The expression of p73( was detected by immunohistochemistry in 41 breast carcinoma tissues, 13 benign breast tumor tissues and 8 normal tissues and 8 normal breast tissues, respectively. Results: The positive expression of p73( was found in 20/41 (48.8%) of breast carcinoma tissues, 1/13 (7.7%) of benign breast tumor tissues. The positive expression rate of p73( in breast carcinoma tissues was significant1y higher than that in benign breast tumor tissues and normal breast tissues (P<0.05). The expression intensity of p73( increased significantly in breast carcinoma tissues compared with benign breast tumor tissues and normal breast tissues (P<0.05). Significant association of the expression of p73( with lymph node metastases and TNM stages of the carcinoma was found (P<0.05). The expression of p73( displayed a positive correlation with p53 (P<0.05). Conclusion: These results suggest that there is an up-regulation of p73( expression in breast carcinoma tissues, which may be implicated in the tumorigenesis of breast carcinoma as a molecular alteration.

  9. The conqueror motif in chapters 12-13: a heavenly and an earthly perspective in the Book of Revelation

    OpenAIRE

    EC Shin

    2007-01-01

    The theme of the conqueror motif in the book of Revelation is one of the prominent themes. The theme of the conqueror motif provides various symbolical messages from an exegetical and theological perspective. An alternative symbolic perspective provides a heavenly perspective and the symbolic transformation. Various images such as salvation for the conquerors and judgment of the evil ones, or victory of the Lamb and defeat of Satan, transform our earthly perspective into the heavenly perspect...

  10. God’s immanency in Abraham’s response to revelation: from providence to omnipresence

    Directory of Open Access Journals (Sweden)

    Ciocan Tudor Cosmin

    2016-03-01

    Full Text Available My assertion is that God’s biblical image may not reflect entirely His existence in itself as well as His revealed image. Even if God in Himself is both transcendent and immanent at the same time, and He is revealing accordingly in the history of humankind, still the image of God constructed in the writings of the Old Testament is merely the perspective made upon God by His followers to whom the He has revealed. That could be the reason why for centuries God’s biblical image seems to emphasize more His immanence, starting with Pentateuch, where God cohabites with Adam on Earth, then He reveals Himself to Abraham and Moses and so on. Somewhere, after the Babylonian exile, the image suffers slightly differences tilting towards God’s transcendence. In a path already created and grounded by Israel’s ancestors, even this new color of transcendence bears the nuances of immanence. How can this be possible? Let’s take a look on the revelation received by Abraham from God and see how this can fit the profile. Instead of the transcendence of God regarded by others in the differentness of Yahweh appointed by Abraham in his walking out of Mesopotamia, I will prove otherwise, that Abraham is on the contrary proving God’s immanency in this very differentness of His in relation with other gods by providence and omnipresence, indwelling His creation.

  11. Targeting γ-secretase in breast cancer

    Directory of Open Access Journals (Sweden)

    Han J

    2012-06-01

    Full Text Available Jianxun Han,1 Qiang Shen21Department of Chemical Engineering and Applied Chemistry, University of Toronto, 2Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, Toronto, Ontario, CanadaAbstract: γ-secretase complexes are multisubunit protease complexes that perform the intramembrane cleavage of more than 60 type-I transmembrane proteins, including Notch receptors. Since dysregulated Notch signaling has been implicated in the tumorigenesis and progression of breast cancer, small molecule γ-secretase inhibitors (GSIs are being tested for their therapeutic potential in breast cancer treatment in several clinical trials. Here, the structure of γ-secretase complex and the development of GSIs are briefly reviewed, the roles of Notch and several other γ-secretase substrates in breast cancer are discussed, and the difference between γ-secretase inhibition and Notch inhibition, as well as the side effects associated with GSIs, are described. A better understanding of molecular mechanisms that affect the responsiveness of breast cancer to GSI might help to develop strategies to enhance the antitumor activity and, at the same time, alleviate the side effects of GSI.Keywords: γ-secretase, GSI, Notch, breast cancer

  12. Breast Gangrene

    Directory of Open Access Journals (Sweden)

    Husasin Irfan

    2011-08-01

    Full Text Available Abstract Background Breast gangrene is rare in surgical practice. Gangrene of breast can be idiopathic or secondary to some causative factor. Antibiotics and debridement are used for management. Acute inflammatory infiltrate, severe necrosis of breast tissue, necrotizing arteritis, and venous thrombosis is observed on histopathology. The aim of was to study patients who had breast gangrene. Methods A prospective study of 10 patients who had breast gangrene over a period of 6 years were analyzed Results All the patients in the study group were female. Total of 10 patients were encountered who had breast gangrene. Six patients presented with breast gangrene on the right breast whereas four had on left breast. Out of 10 patients, three had breast abscess after teeth bite followed by gangrene, one had iatrogenic trauma by needle aspiration of erythematous area of breast under septic conditions. Four had history of application of belladonna on cutaneous breast abscess and had then gangrene. All were lactating female. Amongst the rest two were elderly, one of which was a diabetic who had gangrene of breast and had no application of belladonna. All except one had debridement under cover of broad spectrum antibiotics. Three patients had grafting to cover the raw area. Conclusion Breast gangrene occurs rarely. Etiology is variable and mutifactorial. Teeth bite while lactation and the iatrogenic trauma by needle aspiration of breast abscess under unsterlised conditions could be causative. Uncontrolled diabetes can be one more causative factor for the breast gangrene. Belladonna application as a topical agent could be inciting factor. Sometimes gangrene of breast can be idiopathic. Treatment is antibiotics and debridement.

  13. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells

    International Nuclear Information System (INIS)

    There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massive expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche

  14. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc

    Science.gov (United States)

    Pusapati, Raju V.; Rounbehler, Robert J.; Hong, Sungki; Powers, John T.; Yan, Mingshan; Kiguchi, Kaoru; McArthur, Mark J.; Wong, Paul K.; Johnson, David G.

    2006-01-01

    Overexpression of the c-myc oncogene contributes to the development of a significant number of human cancers. In response to deregulated Myc activity, the p53 tumor suppressor is activated to promote apoptosis and inhibit tumor formation. Here we demonstrate that p53 induction in response to Myc overexpression requires the ataxia-telangiectasia mutated (ATM) kinase, a major regulator of the cellular response to DNA double-strand breaks. In a transgenic mouse model overexpressing Myc in squamous epithelial tissues, inactivation of Atm suppresses apoptosis and accelerates tumorigenesis. Deregulated Myc expression induces DNA damage in primary transgenic keratinocytes and the formation of H2AX and phospho-SMC1 foci in transgenic tissue. These findings suggest that Myc overexpression causes DNA damage in vivo and that the ATM-dependent response to this damage is critical for p53 activation, apoptosis, and the suppression of tumor development. p53 | DNA damage

  15. Role of Dicer on tumorigenesis in glioma cells

    Institute of Scientific and Technical Information of China (English)

    Anling Zhang; Lei Han; Guangxiu Wang; Zhifan Jia; Peiyu Pu; Chunsheng Kang

    2010-01-01

    Micro RNAs(miRNAs)are non-coding,single-stranded RNAs that regulate target gene expression by repressing translation or promoting RNA cleavage.Recent studies show that miRNA expression is globally decreased in some human tumors.Dicer is an essential component of the miRNA processing machinery.To determine whether global reduction of miRNA effects tumorigenesis,small interfering RNA were designed to target Dicer to restrain whole miRNA expression in the glioblastoma cell line-TJ905.With effective knock-down of Dicer,tumor cells were invasive and proliferative,and globally impaired miRNA processing enhanced proliferation and invasiveness of glioma cells in vitro.Suppression of Dicer expression resulted in a more aggressive glioma phenotype,which suggests that global reduction of miRNA expression could have an oncogenic role in glioblastoma cells.

  16. Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver toxicity.

    Science.gov (United States)

    Zhang, Qi; Pan, Jing; North, Paula E; Yang, Shoua; Lubet, Ronald A; Wang, Yian; You, Ming

    2012-05-01

    3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. However, the chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been tested. In this study, we investigated the chemopreventive activity of 3-bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice. We found that 3-bromopyruvate significantly decreased tumor multiplicity and tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given large doses of 3-bromopyruvate, confirmed in this study, we decided to test the chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10 mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate did not accompany any liver toxicity indicating that it is a safer route of administering this compound. Treatment with 3-bromopyruvate increased immunohistochemical staining for cleaved caspase-3, suggesting that the lung tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis. 3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced hexokinase activity, and blocked energy metabolism in cancer cells, finally triggered cancer cell death and induced apoptosis through caspase-3, and PARP in human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung tumorigenesis, in part through induction of apoptosis, merits further investigation of this compound as a chemopreventive agent for human lung cancer. PMID:22401980

  17. New and emerging factors in tumorigenesis: an overview

    Directory of Open Access Journals (Sweden)

    Kim S

    2015-07-01

    Full Text Available Suwon Kim1,2 1Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 2Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA Abstract: This article provides an overview of the genes and cellular processes that have emerged recently as new key factors in tumorigenesis. We review these in the context of three broad categories. First, genome-scale sequencing studies have revealed a set of frequently mutated genes in cancer. Genes that are mutated in >5% of all cancers across tissue types are discussed, with a highlighted focus on the two most frequently mutated genes, TP53 and PIK3CA. Second, the mechanisms of resistance to targeted therapy are reviewed. These include acquired resistance under targeted therapy selection owing to mutations and amplification of genes in the same or parallel signaling pathways. Importantly, sequencing of primary tumors has revealed that therapy-resistant clones already exist prior to targeted therapy, demonstrating that tumor heterogeneity in primary tumors confers a mechanism for inherent therapy resistance. Third, “metastasis-specific genes”, or rather lack thereof, are discussed. While many genes have been shown to be capable of promoting metastasis in experimental systems, no common genetic alterations have been identified specific to metastatic lesions. Rather, the same gene mutations frequently found in primary tumors are also found prevalent in metastases, suggesting that the genes that drive tumorigenesis may also drive metastasis. In this light, an emerging view of metastatic progression is discussed. Collectively, these recent advances in cancer research have refined our knowledge on cancer etiology and progression but also present challenges that will require innovative new approaches to treat and manage cancer. Keywords: cancer, genomics, gene mutations, targeted therapy resistance, tumor heterogeneity, metastasis

  18. PPARδ activation acts cooperatively with 3-phosphoinositide-dependent protein kinase-1 to enhance mammary tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Claire B Pollock

    Full Text Available Peroxisome proliferator-activated receptorδ (PPARδ is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1. PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling.

  19. In vivo fluorescence imaging reveals the promotion of mammary tumorigenesis by mesenchymal stromal cells.

    Directory of Open Access Journals (Sweden)

    Chien-Chih Ke

    Full Text Available Mesenchymal stromal cells (MSCs are multipotent adult stem cells which are recruited to the tumor microenvironment (TME and influence tumor progression through multiple mechanisms. In this study, we examined the effects of MSCs on the tunmorigenic capacity of 4T1 murine mammary cancer cells. It was found that MSC-conditioned medium increased the proliferation, migration, and efficiency of mammosphere formation of 4T1 cells in vitro. When co-injected with MSCs into the mouse mammary fat pad, 4T1 cells showed enhanced tumor growth and generated increased spontaneous lung metastasis. Using in vivo fluorescence color-coded imaging, the interaction between GFP-expressing MSCs and RFP-expressing 4T1 cells was monitored. As few as five 4T1 cells could give rise to tumor formation when co-injected with MSCs into the mouse mammary fat pad, but no tumor was formed when five or ten 4T1 cells were implanted alone. The elevation of tumorigenic potential was further supported by gene expression analysis, which showed that when 4T1 cells were in contact with MSCs, several oncogenes, cancer markers, and tumor promoters were upregulated. Moreover, in vivo longitudinal fluorescence imaging of tumorigenesis revealed that MSCs created a vascularized environment which enhances the ability of 4T1 cells to colonize and proliferate. In conclusion, this study demonstrates that the promotion of mammary cancer progression by MSCs was achieved through the generation of a cancer-enhancing microenvironment to increase tumorigenic potential. These findings also suggest the potential risk of enhancing tumor progression in clinical cell therapy using MSCs. Attention has to be paid to patients with high risk of breast cancer when considering cell therapy with MSCs.

  20. Breast lift

    Science.gov (United States)

    ... One breast that is larger than the other (asymmetry of the breasts) Uneven position of the nipples ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  1. Breast cancer

    Science.gov (United States)

    ... perform breast self-exams each month. However, the importance of self-exams for detecting breast cancer is ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. Prostate-derived ets factor represses tumorigenesis and modulates epithelial-to-mesenchymal transition in bladder carcinoma cells.

    Science.gov (United States)

    Tsui, Ke-Hung; Lin, Yu-Hsiang; Chung, Li-Chuan; Chuang, Sung-Ting; Feng, Tsui-Hsia; Chiang, Kun-Chun; Chang, Phei-Lang; Yeh, Chi-Ju; Juang, Horng-Heng

    2016-05-28

    Prostate-derived Ets (E-twenty six) factor (PDEF), an epithelium-specific member of the Ets family of transcription factors, has been shown to play a role in suppressing the development of many epithelium-derived cancers such as prostate and breast cancer. It is not clear, however, whether PDEF is involved in the development or progression of bladder cancer. In a comparison between normal urothelium and bladder tumor tissue, we identified significant decreases of PDEF in the tumor tissue. Further, the immunohistochemistry assays indicated a significantly higher immunostaining of PDEF in low-grade bladder tumors. Additionally, the highly differentiated transitional-cell bladder carcinoma RT-4 cells expressed significantly more PDEF levels than the bladder carcinoma HT1376 and the T24 cells. Ectopic overexpression of PDEF attenuated proliferation, invasion, and tumorigenesis of bladder carcinoma cells in vitro and in vivo. PDEF enhanced the expression levels of mammary serine protease inhibitor (MASPIN), N-myc downstream regulated gene 1 (NDRG1), KAI1, and B-cell translocation gene 2 (BTG2). PDEF modulated epithelial-mesenchymal-transition (EMT) by upregulating E-cadherin expression and downregulating the expression of N-cadherin, SNAIL, SLUG, and vimentin, leading to lower migration and invasion abilities of bladder carcinoma cells. Filamentous actin (F-actin) polarization and remodeling were observed in PDEF-knockdown RT-4 cells. Our results suggest that PDEF gene expression is associated with the extent of bladder neoplasia and PDEF modulated the expressions of EMT-related genes. The induction of BTG2, NDRG1, MASPIN, and KAI1 gene expressions by PDEF may explain the inhibitory functions of PDEF on the proliferation, invasion, and tumorigenesis in bladder carcinoma cells. PMID:26965996

  3. 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. ...

  4. Ultrasound - Breast

    Science.gov (United States)

    ... Even so, mammograms do not detect all breast cancers. Some breast lesions and abnormalities are not visible or are difficult to interpret on mammograms. In breasts that are dense, meaning there is a lot ... and less fat, many cancers can be hard to see on mammography. Many ...

  5. S100A7 and the progression of breast cancer

    International Nuclear Information System (INIS)

    The S100 gene family comprises more than 20 members whose protein sequences encompass at least one EF-hand Ca2+ binding motif. The expression of individual family members is not ubiquitous for all tissues and there appears to be an element of tissue-specific expression. Molecular analysis of breast tumors has revealed that several S100s, including S100A2, S100A4 and S100A7, exhibit altered expression levels during breast tumorigenesis and/or progression. Subsequent studies have started to describe a functional role for these S100 proteins as well as their mechanism of action and the biochemical pathways they modify. The present review outlines what is known about S100A7 in breast cancer and summarizes the need to better understand the importance of this protein in breast cancer

  6. Transforming growth factor-β and breast cancer: Lessons learned from genetically altered mouse models

    International Nuclear Information System (INIS)

    Transforming growth factor (TGF)-βs are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-βaction in the context of the whole animal. Overexpression of TGF-β can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-β function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-β response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-βs have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-β receptors seen in some human breast hyperplasias may play a causal role in tumor development

  7. MicroRNA analysis of breast ductal fluid in breast cancer patients.

    Science.gov (United States)

    Do Canto, Luisa Matos; Marian, Catalin; Willey, Shawna; Sidawy, Mary; Da Cunha, Patricia A; Rone, Janice D; Li, Xin; Gusev, Yuriy; Haddad, Bassem R

    2016-05-01

    Recent studies suggest that microRNAs show promise as excellent biomarkers for breast cancer; however there is still a high degree of variability between studies making the findings difficult to interpret. In addition to blood, ductal lavage (DL) and nipple aspirate fluids represent an excellent opportunity for biomarker detection because they can be obtained in a less invasive manner than biopsies and circumvent the limitations of evaluating blood biomarkers with regards to tissue of origin specificity. In this study, we have investigated for the first time, through a real-time PCR array, the expression of 742 miRNAs in the ductal lavage fluid collected from 22 women with unilateral breast tumors. We identified 17 differentially expressed miRNAs between tumor and paired normal samples from patients with ductal breast carcinoma. Most of these miRNAs have various roles in breast cancer tumorigenesis, invasion and metastasis, therapeutic response, or are associated with several clinical and pathological characteristics of breast tumors. Moreover, some miRNAs were also detected in other biological fluids of breast cancer patients such as serum (miR-23b, -133b, -181a, 338-3p, -625), plasma (miR-200a), and breast milk (miR-181a). A systems biology analysis of these differentially expressed miRNAs points out possible pathways and cellular processes previously described as having an important role in breast cancer such as Wnt, ErbB, MAPK, TGF-β, mTOR, PI3K-Akt, p53 signaling pathways. We also observed a difference in the miRNA expression with respect to the histological type of the tumors. In conclusion, our findings suggest that miRNA analysis of breast ductal fluid is feasible and potentially very useful for the detection of breast cancer. PMID:26984519

  8. E-cadherin promotor methylation and mutation are inversely related to motility capacity of breast cancer cells

    NARCIS (Netherlands)

    Horssen, R. van; Hollestelle, A.; Rens, J.A.; Eggermont, A.M.; Schutte, M.; Ten Hagen, T.L.

    2012-01-01

    Inactivation of the tumor suppressor E-cadherin is an important event during breast tumorigenesis, as its decreased expression is linked to aggressiveness and metastasis. However, the relationship between the different modes of E-cadherin inactivation (mutation versus promotor hypermethylation) and

  9. The role of mitochondrial tRNA variants in female breast cancer.

    Science.gov (United States)

    Meng, Xian-Li; Meng, Hua; Zhang, Wei; Qin, Yu-Hua; Zhao, Ning-Min

    2016-09-01

    Mitochondrial tRNA (Mt-tRNA) variants have been found to be involved in the carcinogenesis of breast cancer. These tRNAs, which played critical roles in mitochondrial protein synthesis, were important regulators in tumorigenesis. Distinguishing the polymorphisms or mutations in mt-tRNA genes was still puzzling for the clinicians and geneticists when confronted with the breast cancer. In this study, we performed a detailed analysis of recently reported mutations in mt-tRNA genes and further discussed the relationship between these variants and breast cancer. PMID:25703847

  10. Characterization of synergistic anti-cancer effects of docosahexaenoic acid and curcumin on DMBA-induced mammary tumorigenesis in mice

    International Nuclear Information System (INIS)

    The major obstacles to the successful use of individual nutritional compounds as preventive or therapeutic agents are their efficacy and bioavailability. One approach to overcoming this problem is to use combinations of nutrients to induce synergistic effects. The objective of this research was to investigate the synergistic effects of two dietary components: docosahexaenoic acid (DHA), an omega-3 fatty acid present in cold-water fish, and curcumin (CCM), an herbal nutrient present in turmeric, in an in vivo model of DMBA-induced mammary tumorigenesis in mice. We used the carcinogen DMBA to induce breast tumors in SENCAR mice on control, CCM, DHA, or DHA + CCM diets. Appearance and tumor progression were monitored daily. The tumors were harvested 15 days following their first appearance for morphological and immunohistological analysis. Western analysis was performed to determine expression of maspin and survivin in the tumor tissues. Characterization of tumor growth was analyzed using appropriate statistical methods. Otherwise all other results are reported as mean ± SD and analyzed with one-way ANOVA and Tukey’s post hoc procedure. Analysis of gene microarray data indicates that combined treatment with DHA + CCM altered the profile of “PAM50” genes in the SK-BR-3 cell line from an ER-/Her-2+ to that resembling a “normal-like” phenotype. The in vivo studies demonstrated that DHA + CCM treatment reduced the incidence of breast tumors, delayed tumor initiation, and reduced progression of tumor growth. Dietary treatment had no effect on breast size development, but tumors from mice on a control diet (untreated) were less differentiated than tumors from mice fed CCM or DHA + CCM diets. The synergistic effects also led to increased expression of the pro-apoptotic protein, maspin, but reduced expression of the anti-apoptotic protein, survivin. The SK-BR-3 cells and DMBA-induced tumors, both with an ER- and Her-2+ phenotype, were affected by the synergistic

  11. The effects of Fhit on tumorigenesis after multi-exposure to low-dose radiation

    OpenAIRE

    Yu, Xiaoyan; Lu, Lin; Wen, Siyuan; Wang, Ya

    2009-01-01

    Low-dose (≤ 0.1 Gy) radiation could reduce high-dose induced damage including tumorigenesis. However, it remains unclear whether multi-exposure to low-dose radiation at a high dose rate has any risk for increasing tumorigenesis, and whether Fhit plays any role in the process. The purpose of this study is to investigate the effects of multi-exposure to low-dose radiation at a high dose rate on tumorigenesis, and the role of Fhit in it. We irradiated Fhit+/+ and Fhit-/- mice with 1 Gy/1 or 0.1 ...

  12. Aromatase inhibitor strategies in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Heather L McArthur

    2009-07-01

    Full Text Available Heather L McArthur, Patrick G MorrisBreast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: Despite ongoing therapeutic innovations, metastatic breast cancer (MBC remains a treatable but incurable disease. In the developed world, a diagnosis of MBC without a preceding diagnosis of early stage disease is a rare event. However, approximately one-third of women with early stage breast cancer ultimately experience a distant recurrence. Because the majority of breast cancers express estrogen and/or progesterone receptors and are accordingly considered hormone-sensitive, therapeutic strategies that interfere with hormone-mediated tumorigenesis have been a cornerstone of the breast cancer management paradigm for decades. Historically, the selective estrogen receptor modulator tamoxifen has been the most extensively studied and widely used hormone maneuver in breast cancer. However, a recent therapeutic innovation, namely the successful development of third-generation aromatase inhibitors (AIs, has had a dramatic impact on the treatment paradigm for women with hormone-sensitive MBC. Because of the demonstrated efficacy in postmenopausal breast cancer patients, the generally favorable side-effect profile, and the convenience of oral administration, AIs are now in widespread clinical use. Currently, there are three clinically available third-generation AIs: two reversible, nonsteroidal AIs, letrozole and anastrozole; and one irreversible, steroidal AI, exemestane. All three agents are at least as efficacious as tamoxifen as monotherapy for postmenopausal women with hormone-sensitive MBC. Current clinical research aims to improve upon existing strategies by evaluating AIs in combination with systemic chemotherapy regimens and/or novel targeted agents. It is hoped that these therapeutic innovations will lead to ongoing improvements in quality of life parameters and ideally survival for women

  13. The role of composition in the interpretation of the Rider on the white horse and the seven seals in Revelation

    Directory of Open Access Journals (Sweden)

    Pieter G.R. de Villiers

    2004-11-01

    Full Text Available The article investigates the way in which the author of Revelation composed the seven seals: Formal elements group the seals in smaller patterns. It then explains how this reading of the composition contributes to the process of interpretation by analysing the Rider on the white horse as first seal. Other aspects of the author’s compositional skills are brought into discussion in a last part of the article where the meaning of the Rider on the white horse and the ambiguity of the symbols are discussed.

  14. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    Science.gov (United States)

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  15. 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 ...

  16. 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 ...

  17. Breast Cancer Screening

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Screening (PDQ®)–Patient Version What is screening? Screening ... cancer screening: Cancer Screening Overview General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  18. Identification of novel high-frequency DNA methylation changes in breast cancer.

    Directory of Open Access Journals (Sweden)

    Jared M Ordway

    Full Text Available Recent data have revealed that epigenetic alterations, including DNA methylation and chromatin structure changes, are among the earliest molecular abnormalities to occur during tumorigenesis. The inherent thermodynamic stability of cytosine methylation and the apparent high specificity of the alterations for disease may accelerate the development of powerful molecular diagnostics for cancer. We report a genome-wide analysis of DNA methylation alterations in breast cancer. The approach efficiently identified a large collection of novel differentially DNA methylated loci (approximately 200, a subset of which was independently validated across a panel of over 230 clinical samples. The differential cytosine methylation events were independent of patient age, tumor stage, estrogen receptor status or family history of breast cancer. The power of the global approach for discovery is underscored by the identification of a single differentially methylated locus, associated with the GHSR gene, capable of distinguishing infiltrating ductal breast carcinoma from normal and benign breast tissues with a sensitivity and specificity of 90% and 96%, respectively. Notably, the frequency of these molecular abnormalities in breast tumors substantially exceeds the frequency of any other single genetic or epigenetic change reported to date. The discovery of over 50 novel DNA methylation-based biomarkers of breast cancer may provide new routes for development of DNA methylation-based diagnostics and prognostics, as well as reveal epigenetically regulated mechanism involved in breast tumorigenesis.

  19. Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Feng-Chi Chen

    2014-12-01

    Full Text Available Alternative RNA structures (ARSs, or alternative transcript isoforms, are critical for regulating cellular phenotypes in humans. In addition to generating functionally diverse protein isoforms from a single gene, ARS can alter the sequence contents of 5'/3' untranslated regions (UTRs and intronic regions, thus also affecting the regulatory effects of these regions. ARS may introduce premature stop codon(s into a transcript, and render the transcript susceptible to nonsense-mediated decay, which in turn can influence the overall gene expression level. Meanwhile, ARS can regulate the presence/absence of upstream open reading frames and microRNA targeting sites in 5'UTRs and 3'UTRs, respectively, thus affecting translational efficiencies and protein expression levels. Furthermore, since ARS may alter exon-intron structures, it can influence the biogenesis of intronic microRNAs and indirectly affect the expression of the target genes of these microRNAs. The connections between ARS and multiple regulatory mechanisms underline the importance of ARS in determining cell fate. Accumulating evidence indicates that ARS-coupled regulations play important roles in tumorigenesis. Here I will review our current knowledge in this field, and discuss potential future directions.

  20. Intricacies of hedgehog signaling pathways: A perspective in tumorigenesis

    International Nuclear Information System (INIS)

    The hedgehog (HH) signaling pathway is a crucial negotiator of developmental proceedings in the embryo governing a diverse array of processes including cell proliferation, differentiation, and tissue patterning. The overall activity of the pathway is significantly curtailed after embryogenesis as well as in adults, yet it retains many of its functional capacities. However, aberration in HH signaling mediates the initiation, proliferation and continued sustenance of malignancy in different tissues to varying degrees through different mechanisms. In this review, we provide an overview of the role of constitutively active aberrant HH signaling pathway in different types of human cancer and the underlying molecular and genetic mechanisms that drive tumorigenesis in that particular tissue. An insight into the various modes of anomalous HH signaling in different organs will provide a comprehensive knowledge of the pathway in these tissues and open a window for individually tailored, tissue-specific therapeutic interventions. The synergistic cross talking of HH pathway with many other regulatory molecules and developmentally inclined signaling pathways may offer many avenues for pharmacological advances. Understanding the molecular basis of abnormal HH signaling in cancer will provide an opportunity to inhibit the deregulated pathway in many aggressive and therapeutically challenging cancers where promising options are not available.

  1. Intricacies of hedgehog signaling pathways: A perspective in tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kar, Swayamsiddha; Deb, Moonmoon; Sengupta, Dipta; Shilpi, Arunima; Bhutia, Sujit Kumar [Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008 (India); Patra, Samir Kumar, E-mail: samirp@nitrkl.ac.in [Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008 (India)

    2012-10-01

    The hedgehog (HH) signaling pathway is a crucial negotiator of developmental proceedings in the embryo governing a diverse array of processes including cell proliferation, differentiation, and tissue patterning. The overall activity of the pathway is significantly curtailed after embryogenesis as well as in adults, yet it retains many of its functional capacities. However, aberration in HH signaling mediates the initiation, proliferation and continued sustenance of malignancy in different tissues to varying degrees through different mechanisms. In this review, we provide an overview of the role of constitutively active aberrant HH signaling pathway in different types of human cancer and the underlying molecular and genetic mechanisms that drive tumorigenesis in that particular tissue. An insight into the various modes of anomalous HH signaling in different organs will provide a comprehensive knowledge of the pathway in these tissues and open a window for individually tailored, tissue-specific therapeutic interventions. The synergistic cross talking of HH pathway with many other regulatory molecules and developmentally inclined signaling pathways may offer many avenues for pharmacological advances. Understanding the molecular basis of abnormal HH signaling in cancer will provide an opportunity to inhibit the deregulated pathway in many aggressive and therapeutically challenging cancers where promising options are not available.

  2. DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis.

    Science.gov (United States)

    Png, C W; Weerasooriya, M; Guo, J; James, S J; Poh, H M; Osato, M; Flavell, R A; Dong, C; Yang, H; Zhang, Y

    2016-01-14

    Dual specificity phosphatase 10 (DUSP10), also known as MAP kinase phosphatase 5 (MKP5), negatively regulates the activation of MAP kinases. Genetic polymorphisms and aberrant expression of this gene are associated with colorectal cancer (CRC) in humans. However, the role of DUSP10 in intestinal epithelial tumorigenesis is not clear. Here, we showed that DUSP10 knockout (KO) mice had increased intestinal epithelial cell (IEC) proliferation and migration and developed less severe colitis than wild-type (WT) mice in response to dextran sodium sulphate (DSS) treatment, which is associated with increased ERK1/2 activation and Krüppel-like factor 5 (KLF5) expression in IEC. In line with increased IEC proliferation, DUSP10 KO mice developed more colon tumours with increased severity compared with WT mice in response to administration of DSS and azoxymethane (AOM). Furthermore, survival analysis of CRC patients demonstrated that high DUSP10 expression in tumours was associated with significant improvement in survival probability. Overexpression of DUSP10 in Caco-2 and RCM-1 cells inhibited cell proliferation. Our study showed that DUSP10 negatively regulates IEC growth and acts as a suppressor for CRC. Therefore, it could be targeted for the development of therapies for colitis and CRC. PMID:25772234

  3. Hemolytic E. coli Promotes Colonic Tumorigenesis in Females.

    Science.gov (United States)

    Jin, Ye; Tang, Senwei; Li, Weilin; Ng, Siew Chien; Chan, Michael W Y; Sung, Joseph J Y; Yu, Jun

    2016-05-15

    Bacterial infection is linked to colorectal carcinogenesis, but the species that contribute to a protumorigenic ecology are ill-defined. Here we report evidence that α-hemolysin-positive (hly(+)) type I Escherichia coli (E. coli) drives adenomagenesis and colorectal cancer in human females but not males. We classified E. coli into four types using a novel typing method to monitor fimH mutation patterns of fecal isolates from adenoma patients (n= 59), colorectal cancer patients (n= 83), and healthy subjects (n= 85). hly(+) type I E. coli was found to be relatively more prevalent in stools from females with adenoma and colorectal cancer, correlating with poor survival in colorectal cancer patients. In mechanistic studies in female mice, we found that hly(+) type 1 E. coli activated expression of the glucose transporter GLUT1 and repressed expression of the tumor suppressor BIM. hly-encoded alpha hemolysin partially accounted for these effects by elevating the levels of HIF1α. Notably, colon tumorigenesis in mice could be promoted by feeding hly(+) type I E. coli to female but not male subjects. Collectively, our findings point to hemolytic type I E. coli as a candidate causative factor of colorectal cancer in human females, with additional potential as a biomarker of disease susceptibility. Cancer Res; 76(10); 2891-900. ©2016 AACR. PMID:27013198

  4. Sur8 mediates tumorigenesis and metastasis in colorectal cancer

    Science.gov (United States)

    Lee, Young-Mi; Kaduwal, Saluja; Lee, Kug Hwa; Park, Jong-Chan; Jeong, Woo-Jeong; Choi, Kang-Yell

    2016-01-01

    Sur8, a scaffold protein of the Ras pathway, interacts with Ras and Raf and modulates the Ras-extracellular signal-regulated kinase (ERK) pathway. Here we show that Sur8 is overexpressed in established human colorectal cancer (CRC) cell lines and CRC patient tissues. Moreover, Sur8 expression is increased during liver metastasis in CRC patients. Sur8 knockdown decreases ERK and Akt activities in CRC cell lines, regardless of their K-Ras, B-Raf or PI3K mutation status. Overexpression or knockdown of Sur8 increases or decreases, respectively, the proliferation or transformation of CRC cell lines. Sur8 knockdown attenuates the migration and invasion of HCT116 CRC cells. Subcutaneous or orthotopic injection of HCT116 cells harboring a doxycycline (Dox)-mediated Sur8 knockdown system in nude mice resulted in decreased tumorigenic potential and inhibited the liver metastatic potential of HCT116 cells. Taken together, our data support the role of Sur8 as a promoter of tumorigenesis and liver metastasis in CRC through its modulation of the Ras-ERK and PI3K-Akt signaling pathways. PMID:27469030

  5. Molecular genetics of cancer and tumorigenesis: Drosophila models

    Institute of Scientific and Technical Information of China (English)

    Wu-Min Deng

    2011-01-01

    Why do some cells not respond to normal control of cell division and become tumorous? Which signals trigger some tumor cells to migrate and colonize other tissues? What genetic factors are responsible for tumorigenesis and cancer development? What environmental factors play a role in cancer formation and progression? In how many ways can our bodies prevent and restrict the growth of cancerous cells?How can we identify and deliver effective drugs to fight cancer? In the fight against cancer,which kills more people than any other disease,these and other questions have long interested researchers from a diverse range of fields.To answer these questions and to fight cancer more effectively,we must increase our understanding of basic cancer biology.Model organisms,including the fruit fly Drosophila melanogaster,have played instrumental roles in our understanding of this devastating disease and the search for effective cures.Drosophila and its highly effective,easy-touse,and ever-expanding genetic tools have contributed toand enriched our knowledge of cancer and tumor formation tremendously.

  6. Heat-shock proteins in infection-mediated inflammation-induced tumorigenesis

    OpenAIRE

    Li Zihai; Goldstein Mark G

    2009-01-01

    Abstract Inflammation is a necessary albeit insufficient component of tumorigenesis in some cancers. Infectious agents directly implicated in tumorigenesis have been shown to induce inflammation. This process involves both the innate and adaptive components of the immune system which contribute to tumor angiogenesis, tumor tolerance and metastatic properties of neoplasms. Recently, heat-shock proteins have been identified as mediators of this inflammatory process and thus may provide a link b...

  7. Survival and tumorigenesis in O6-methylguanine DNA methyltransferase-deficient mice following cyclophosphamide exposure

    OpenAIRE

    Nagasubramanian, Ramamoorthy; Hansen, Ryan J.; Delaney, Shannon M.; Cherian, Mathew M.; Samson, Leona D.; Kogan, Scott C.; Dolan, M. Eileen

    2008-01-01

    O6-methylguanine DNA methyltransferase (MGMT) deficiency is associated with an increased susceptibility to alkylating agent toxicity. To understand the contribution of MGMT in protecting against cyclophosphamide (CP)-induced toxicity, mutagenesis and tumorigenesis, we compared the biological effects of this agent in transgenic Mgmt knockout and wild-type mice. In addition, neurofibromin (Nf1)+/− background was used to increase the likelihood of CP-induced tumorigenesis. Cohorts of Mgmt-profic...

  8. Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival

    OpenAIRE

    Zell, Jason A.; Ignatenko, Natalia A.; Yerushalmi, Hagit F; Ziogas, Argyrios; Besselsen, David G; Gerner, Eugene W.; Anton-Culver, Hoda

    2007-01-01

    Elevated polyamine and nitric oxide levels (both derived from arginine) promote tumorigenesis, whereas non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal cancer (CRC) incidence in experimental and epidemiologic studies. We investigated dietary arginine-induced intestinal tumorigenesis and NSAID-inhibitory effects in Apc(Min/+) mice differentially expressing nitric oxide synthase-2 (Nos2). We also studied effects of estimated arginine exposures through meat consumption on tumor ...

  9. Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

    Science.gov (United States)

    Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B.; Wang, Ya

    2016-06-01

    Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

  10. Update on clinical trials: genetic targets in breast cancer.

    Science.gov (United States)

    Lim, Bora; Cream, Leah V; Harvey, Harold A

    2013-01-01

    Breast cancer is the most commonly diagnosed cancer in women in United States. From data of American Cancer Society from 2007 reported total of 178,480 women diagnosed with breast cancer. The death rate from breast cancer has decreased in North America over time, but still accounts for second highest cancer death, following lung cancer. Breast cancer is staged based on tumor size, nodal involvement, and distant metastasis like any other solid tumors. However clinical staging is not the only important factor in management of breast cancer. Various molecular features divides breast cancer into many subgroups - that act differently, and respond differently from therapy. Thus the focus of breast cancer treatment has evolved focusing on specific targets. The most important biologic markers in subtyping of breast cancer so far are hormone receptor positivity and HER2/neu protein expression. Five molecular subtypes using intrinsic gene set include Basal mRNA, HER2 + mRNA, Luminal AmRNA, Luminal B mRNA, and Normal-like mRNA. In addition, better understanding of genetic target of breast cancer has given us arsenal of personalized, and more effective treatment approach.This review will focus on examples that highlight several mechanism of tumorigenesis, giving us not just understanding of gene pathways and the molecular biology, that could lead us to therapeutic target. Several important molecular targets have been investigated in preclinical and clinical trials, others are yet to be explored. We will also describe genetic mechanisms discovery related to overcoming resistance to current targeted therapies in breast cancer, including hormone receptor expression and HER 2- neu amplification. We will also review other exciting developments in understanding of breast cancer, the tumor microenvironment and cancer stem cells, and targeting agents in that area. PMID:23288634

  11. Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

    Directory of Open Access Journals (Sweden)

    Aurelie de Thonel

    2011-03-01

    Full Text Available Heat Shock Factors (HSF form a family of transcription factors (four in mammals which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents.

  12. Molecular mechanisms of thyroid tumorigenesis; Molekulare Mechanismen der Schilddruesentumorgenese

    Energy Technology Data Exchange (ETDEWEB)

    Krause, K.; Fuehrer, D. [Universitaetsklinikum Leipzig (Germany). Abt. fuer Endokrinolgoie, Diabetologie und Nephrologie

    2008-09-15

    Thyroid nodules are the most frequent endocrine disorder and occur in approximately 30% of the German population. Thyroid nodular disease constitutes a very heterogeneous entity. A striking diversity of possible functional and morphological features of a thyroid tumour derived from the same thyroid ancestor cell, is a hallmark of thyroid tumorigenesis and is due to specific genetic alterations. Defects in known candidate genes can be found in up to 70% of differentiated thyroid carcinomas and determine the respective cancer phenotype. Papillary thyroid cancers (PTC) harbour BRAF (or much less frequently RAS) mutations in sporadically occurring tumours, while radiation-induced PTC display chromosomal rearrangements such as RET, TRK, APR9 / BRAF. These genetic events results in constitutive MAPKinase activation. Follicular thyroid cancers (FTC) harbour RAS mutations or PAX8/ PPAR{gamma} rearrangements, both of which, however have also been identified in follicular adenoma. In addition, recent studies show, that activation of PI3K/AKT signalling occurs with high frequency in follicular thyroid tumours. Undifferentiated (anaplastic) thyroid cancers (ATC) display genetic features of FTC or PTC, in addition to aberant activation of multiple tyrosinkinase pathways (overexpression or mutations in PI3K and MAPK pathways). This underscores the concept of a sequential evolution of ATC from differentiated thyroid cancer, a process widely conceived to be triggered by p53 inactivation. In contrast, the molecular pathogenesis of benign thyroid tumours, in particular cold thyroid nodules is less known, except for toxic thyroid nodules, which arise from constitutive activation of cAMP signalling, predominantly through TSHR mutations. (orig.)

  13. Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

    Energy Technology Data Exchange (ETDEWEB)

    Thonel, Aurelie de [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); Mezger, Valerie, E-mail: valerie.mezger@univ-paris-diderot.fr [CNRS, UMR7216 Epigenetics and Cell Fate, Paris (France); University Paris Diderot, 75013 Paris (France); Garrido, Carmen, E-mail: valerie.mezger@univ-paris-diderot.fr [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); CHU, Dijon BP1542, Dijon (France)

    2011-03-07

    Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents.

  14. Conserved mechanisms of tumorigenesis in the Drosophila adult midgut.

    Directory of Open Access Journals (Sweden)

    Òscar Martorell

    Full Text Available Whereas the series of genetic events leading to colorectal cancer (CRC have been well established, the precise functions that these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducing benign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Ras mutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila's intestines share many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activation of the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show that compound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-like outgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of cell differentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markers present in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration in intestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeutic compounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila, providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation and progression.

  15. Genetic Manipulation of Homologous Recombination In Vivo Attenuates Intestinal Tumorigenesis.

    Science.gov (United States)

    McIlhatton, Michael A; Murnan, Kevin; Carson, Daniel; Boivin, Gregory P; Croce, Carlo M; Groden, Joanna

    2015-07-01

    Although disruption of DNA repair capacity is unquestionably associated with cancer susceptibility in humans and model organisms, it remains unclear if the inherent tumor phenotypes of DNA repair deficiency syndromes can be regulated by manipulating DNA repair pathways. Loss-of-function mutations in BLM, a member of the RecQ helicase family, cause Bloom's syndrome (BS), a rare, recessive genetic disorder that predisposes to many types of cancer. BLM functions in many aspects of DNA homeostasis, including the suppression of homologous recombination (HR) in somatic cells. We investigated whether BLM overexpression, in contrast with loss-of-function mutations, attenuated the intestinal tumor phenotypes of Apc(Min/+) and Apc(Min/+);Msh2(-/-) mice, animal models of familial adenomatous polyposis coli (FAP). We constructed a transgenic mouse line expressing human BLM (BLM-Tg) and crossed it onto both backgrounds. BLM-Tg decreased adenoma incidence in a dose-dependent manner in our Apc(Min/) (+) model of FAP, although levels of GIN were unaffected and concomitantly increased animal survival over 50%. It did not reduce intestinal tumorigenesis in Apc(Min/) (+);Msh2(-/-) mice. We used the pink-eyed unstable (p(un)) mouse model to demonstrate that increasing BLM dosage in vivo lowered endogenous levels of HR by 2-fold. Our data suggest that attenuation of the Min phenotype is achieved through a direct effect of BLM-Tg on the HR repair pathway. These findings demonstrate that HR can be manipulated in vivo to modulate tumor formation at the organismal level. Our data suggest that lowering HR frequencies may have positive therapeutic outcomes in the context of specific hereditary cancer predisposition syndromes, exemplified by FAP. PMID:25908507

  16. 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.

  17. Breast dosimetry

    International Nuclear Information System (INIS)

    The estimation of the absorbed dose to the breast is an important part of the quality control of the mammographic examination. Knowledge of breast dose is essential for the design and performance assessment of mammographic imaging systems. This review gives a historical introduction to the measurement of breast dose. The mean glandular dose (MGD) is introduced as an appropriate measure of breast dose. MGD can be estimated from measurements of the incident air kerma at the surface of the breast and the application of an appropriate conversion factor. Methods of calculating and measuring this conversion factor are described and the results discussed. The incident air kerma itself may be measured for patients or for a test phantom simulating the breast. In each case the dose may be determined using TLD measurements, or known exposure parameters and measurements of tube output. The methodology appropriate to each case is considered and the results from sample surveys of breast dose are presented. Finally the various national protocols for breast dosimetry are compared

  18. Breast cancer

    International Nuclear Information System (INIS)

    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.)

  19. 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.

  20. Different Identity Revelation Modes in an Online Peer-Assessment Learning Environment: Effects on Perceptions toward Assessors, Classroom Climate and Learning Activities

    Science.gov (United States)

    Yu, Fu-Yun; Wu, Chun-Ping

    2011-01-01

    The effects of four different identity revelation modes (three fixed modes: real-name, anonymity, nickname and one dynamic user self-choice mode) on participants' perceptions toward their assessors, classroom climate, and past experience with the learning activity in which they were engaged were examined. A pretest-posttest quasi-experimental…

  1. Phytoalexins, miRNAs and breast cancer: a review of phytochemical-mediated miRNA regulation in breast cancer.

    Science.gov (United States)

    Tilghman, Syreeta L; Rhodes, Lyndsay V; Bratton, Melyssa R; Carriere, Patrick; Preyan, Lynez C; Boue, Stephen M; Vasaitis, Tadas Sean; McLachlan, John A; Burow, Matthew E

    2013-02-01

    There is growing interest in the diverse signaling pathways that regulate and affect breast tumorigenesis, including the role of phytochemicals and the emerging role of microRNAs (miRNAs). Recent studies demonstrate that miRNAs regulate fundamental cellular and developmental processes at the transcriptional and translational level under normal and disease conditions. While there is growing evidence to support the role of phytoalexin-mediated miRNA regulation of cancer, few reports address this role in breast cancer. Recent reports by our group and others demonstrate that natural products, including stilbenes, curcumin, and glyceollins, could alter the expression of specific miRNAs, which may lead to increased sensitivity of cancer cells to conventional anti-cancer agents and, therefore, hormone-dependent and hormone-independent tumor growth inhibition. This review will discuss how dietary intake of natural products, by regulating specific miRNAs, contribute to the prevention and treatment of breast cancer. PMID:23395943

  2. Radiation induced chromosomal instability in peripheral blood lymphocytes obtained from breast cancer patients

    International Nuclear Information System (INIS)

    If the breast cancer patients include a disproportionately large number of radiosensitive persons, some radiation-related genes may be involved in the mammary tumorigenesis. To test this hypothesis, the in vitro radiation sensitivities of peripheral blood lymphocytes obtained from 48 normal females and 131 breast cancer patients were measured with a cytokinesis-blocking micronucleus assay. Both the spontaneous- and the X-ray-induced-micronucleus frequencies in patients' blood were significantly higher than those in normal individuals. Our data demonstrate that the chromosomal instability is higher in patients' cells than in normal individuals' cells, and that the radiation-related genes with low penetrance may be involved in mammary tumorigenesis and also, in patients' radiation susceptibility. (author)

  3. Embodied Revelation: A Classic Grounded Theory of Heart Failure Patient Decision Making Surrounding Primary Prevention Implantable Cardioverter Defibrillator Therapy

    Directory of Open Access Journals (Sweden)

    Vera Barton-Caro Ph.D.,

    2015-12-01

    Full Text Available The purpose of this classic grounded theory study was to explain the complex decision making process of heart failure (HF patients considering primary prevention implantable cardioverter defibrillator (ICD therapy. Sudden cardiac death (SCD is the leading cause of death for people with HF as well as the primary cause of death in the United States (US. ICDs represent the standard of care as the only effective therapy for primary prevention of SCD. However, a significant proportion of qualifying HF patients declines this invasive, yet life-saving device. The grounded theory is of Embodied revelation. The threat of SCD for ICD candidates consists of four stages: living in conscious denial, heightening of awareness, sanctioning ICD therapy, and living in new assurance. The first stage ends abruptly with the critical juncture of grasping the threat of SCD. This grounded theory has implications for research, nursing and medical practice, as well as bioethical considerations.

  4. Individual preferences revelation mechanism and incentive to choose green electricity: an analysis of the consumer decision process

    International Nuclear Information System (INIS)

    Marketing opening in the electric sector and green electricity products supply increase opportunity for households to voluntarily support renewable energy production. Despite the general development of committed actions, and in the lack of public intervention on prices, subscription rates are strongly below consumers' interest announcements and stated willingness to pay. This thesis analyses green electricity subscription factors: how to promote subscription in the case of individual sensitive and rather favourable attitude toward green electricity? Is it possible to encourage preference revelation? Answering these questions requires combining economics analysis and psychological concepts. In that aim, we employ the Theory of Planned Behavior, a social psychology model able to articulate theoretical analysis, psychological concepts and an empirical survey carried out in St Gallen (Switzerland). This survey is based on experimental method and commits, firstly, in testing our hypothesis, secondly in providing a method to influence individual beliefs in order to reinforce subscription intention. Finally, the survey is employed as an incentive tool for concretizing the intention and then promoting individual subscription. We determine that even though the premium to be paid may be an obstacle to subscription, other behavioral and attitudinal factors can explain the construction of individual preferences, intention and action. Analysing the various green electricity demand motivations as well as supply determinants enables to introduce the concept of 'certainty of subscription benefit'. The more the consciousness of personal benefit, the less price an obstacle to subscribe. As a result, our work aims firstly at providing analytical explanations to decision makers concerning the origin of the voluntary individual contribution to public goods as the environment, secondly, at developing green electricity preferences revelation mechanism. This kind of analysis is

  5. The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Ginsburg Erika

    2010-05-01

    ,759 of approximately 8,000 identified were in common. In the AA dataset, proteins associated with breast cancer were primarily related to tumorigenesis/neoplasia, while CAU unique proteins were involved with growth/metastasis. Using a novel mass spectrometry method, 17 biologically active hormones were measured; estradiol, estriol and 2-methoxyestrone were significantly higher in CAU breast tissue. Conclusions This study details normal premenopausal breast tissue composition, delineates potential mechanisms for breast cancer development, and provides data for further investigation into the role of the microenvironment in cancer disparities.

  6. 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 ... recommendations for ovarian ablation . Hormonal therapy for metastatic breast cancer Hormonal therapies are also commonly used to treat ...

  7. Surgery for Breast Cancer

    Science.gov (United States)

    ... Next Topic Breast-conserving surgery (lumpectomy) Surgery for breast cancer Most women with breast cancer have some type ... Relieve symptoms of advanced cancer Surgery to remove breast cancer There are two main types of surgery to ...

  8. Learning about Breast Cancer

    Science.gov (United States)

    ... genetic terms used on this page Learning About Breast Cancer What do we know about heredity and breast ... Cancer What do we know about heredity and breast cancer? Breast cancer is a common disease. Each year, ...

  9. Filariasis of The Breast

    OpenAIRE

    Subhash Bhardwaj, Deepti Mahajan,MRAttri*

    2007-01-01

    Filariasis of the breast presenting as a breast lump and clinically simulating a breast cancer is an unusualpresentation. The present case is of a 42 year old female whose breast lump was excised and histopathologyrevealed filariasis.

  10. Activation of the ATM-Snail pathway promotes breast cancer metastasis

    OpenAIRE

    Sun, Mianen; Guo, Xiaojing; Qian, Xiaolong; Wang, Haibo; Yang, Chunying; Brinkman, Kathryn L; Serrano-Gonzalez, Monica; Jope, Richard S.; Zhou, Binhua; Engler, David A.; Zhan, Ming; Wong, Stephen T. C.; Fu, Li; Xu, Bo

    2012-01-01

    The DNA damage response (DDR) is critical for the maintenance of genetic stability and serves as an anti-cancer barrier during early tumorigenesis. However, the role of the DDR in tumor progression and metastasis is less known. Here, we demonstrate that the ATM kinase, one of the critical DDR elements, is hyperactive in late stage breast tumor tissues with lymph-node metastasis and this hyperactivity correlates with elevated expression of the epithelial–mesenchymal transition marker, Snail. A...

  11. Implications of the Cancer Stem-Cell Hypothesis for Breast Cancer Prevention and Therapy

    OpenAIRE

    Kakarala, Madhuri; Wicha, Max S.

    2008-01-01

    Recent research in breast biology has provided support for the cancer stem-cell hypothesis. Two important components of this hypothesis are that tumors originate in mammary stem or progenitor cells as a result of dysregulation of the normally tightly regulated process of self-renewal. As a result, tumors contain and are driven by a cellular subcomponent that retains key stem-cell properties including self-renewal, which drives tumorigenesis and differentiation that contributes to cellular het...

  12. Attenuating Tumour Angiogenesis: A Preventive Role of Metformin against Breast Cancer

    OpenAIRE

    Shan Gao; Jingcheng Jiang; Pan Li; Huijuan Song; Weiwei Wang; Chen Li; Deling Kong

    2015-01-01

    Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour ...

  13. Breast Cancer

    Science.gov (United States)

    ... click the brackets in the lower right-hand corner of the video screen. To reduce the videos, ... with breast cancer are under way. With early detection, and prompt and appropriate treatment, the outlook for ...

  14. Breast cancer

    International Nuclear Information System (INIS)

    This article is about the diagnosis, treatment and monitoring of breast cancer. Positive diagnosis is based on clinical mammary exam, mammography, mammary ultrasonography, and histological study. Before the chemotherapy and radiotherapy treatment are evaluated the risks

  15. Breast ultrasound

    Science.gov (United States)

    Hacker NF, Friedland ML. Breast disease. In: Hacker NF, Gambone JC, Hobel CJ, eds. Hacker and Moore's Essentials of Obstetrics and Gynecology . 6th ed. Philadelphia, PA: Elsevier; 2016:chap 30. Harvey ...

  16. Breast lump

    Science.gov (United States)

    ... Textbook of Surgery . 19th ed. St. Louis, MO: Elsevier Saunders; 2012:chap 36. Jacobs L, Hardin R. ... eds. Current Surgical Therapy . 11th ed. Philadelphia, PA: Elsevier Saunders; 2014:565-567. Swartz MH. The breast. ...

  17. Breast Density and Your Breast Mammogram Report

    Science.gov (United States)

    Breast Density and Your Mammogram Report Regular mammograms are the best way to find breast cancer early. But if ... But in some women, there’s little change. Breast density is very common, and is not abnormal. How ...

  18. Screening for Breast Problems

    Science.gov (United States)

    ... a clinical breast exam done? • What is breast self-awareness? • How is breast self-awareness different from the traditional breast self-exam? •Glossary ... problems includes mammography , clinical breast exams, and breast self-awareness. What is mammography? Mammography is an X-ray ...

  19. Breast hamartoma

    International Nuclear Information System (INIS)

    Hamartoma of the breast is a rare circumscribed lesion composed of fat and other breast tissue which may be normal or which may show various benign changes. Pathognomonic mammographic features are non-homogenous mass containing mottled densities corresponding to fat, epithelium and connective tissue. In this report, radiological, pathological and histological findings are described. The lesions are usually diagnosed radiologically and accurate diagnosis is necessary for the patient's management and prognosis

  20. Dietary Glycemic Load and Breast Cancer Risk in the Women’s Health Study

    OpenAIRE

    Higginbotham, Susan; Zhang, Zuo-Feng; Lee, I-Min; Cook, Nancy R.; Buring, Julie E.; Liu, Simin

    2004-01-01

    A diet with a high glycemic load (GL) may contribute to a metabolic environment that enhances tumorigenesis. Little is known, however, about whether high glycemic diets increase breast cancer risk in women. We examined the associations between baseline measurements of dietary GL and overall glycemic index (GI) and subsequent breast cancer in a cohort of 39,876 women, ages 45 years or older, participating in the Women’s Health Study. During a mean of 6.8 years of follow-up there were 946 confi...

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

    International Nuclear Information System (INIS)

    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

  2. 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.

  3. 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.

  4. Ubiquitin C-Terminal Hydrolase L1 in Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Jennifer Hurst-Kennedy

    2012-01-01

    Full Text Available Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1, aka PGP9.5 is an abundant, neuronal deubiquitinating enzyme that has also been suggested to possess E3 ubiquitin-protein ligase activity and/or stabilize ubiquitin monomers in vivo. Recent evidence implicates dysregulation of UCH-L1 in the pathogenesis and progression of human cancers. Although typically only expressed in neurons, high levels of UCH-L1 have been found in many nonneuronal tumors, including breast, colorectal, and pancreatic carcinomas. UCH-L1 has also been implicated in the regulation of metastasis and cell growth during the progression of nonsmall cell lung carcinoma, colorectal cancer, and lymphoma. Together these studies suggest UCH-L1 has a potent oncogenic role and drives tumor development. Conversely, others have observed promoter methylation-mediated silencing of UCH-L1 in certain tumor subtypes, suggesting a potential tumor suppressor role for UCH-L1. In this paper, we provide an overview of the evidence supporting the involvement of UCH-L1 in tumor development and discuss the potential mechanisms of action of UCH-L1 in oncogenesis.

  5. Zebrafish pten genes have overlapping and non-redundant functions in tumorigenesis and embryonic development.

    NARCIS (Netherlands)

    Faucherre, A.F.J.A.; Taylor, G.S.; Overvoorde, J.; Dixon, J.E.; den Hertog, J.

    2008-01-01

    In human cancer, PTEN (Phosphatase and TENsin homolog on chromosome 10, also referred to as MMAC1 and TEP1) is a frequently mutated tumor suppressor gene. We have used the zebrafish as a model to investigate the role of Pten in embryonic development and tumorigenesis. The zebrafish genome encodes tw

  6. A local basis for progesterone action during mammary tumorigenesis - no longer RANK and file

    OpenAIRE

    Petrie, Whitney K; Hovey, Russell C

    2011-01-01

    Two recent reports provide compelling insights into the role for RANK and its ligand, RANKL, in progestin-dependent mammary tumorigenesis. These findings build upon a considerable body of evidence pointing to the RANK signaling pathway as being a key mediator of progestin action in the mammary glands.

  7. The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice

    International Nuclear Information System (INIS)

    Ets transcription factors have been widely implicated in the control of tumorigenesis, with most studies suggesting tumor-promoting roles. However, few studies have examined Ets tumorigenesis-modifying functions in vivo using model genetic systems. Using mice expressing a previously characterized Ets dominant repressor transgene in the intestinal epithelium (Villin-En/Erm), we examined the consequences of blocking endogenous Ets-mediated transcriptional activation on tumorigenesis in the ApcMin model of intestinal carcinoma. En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in ApcMin animals. Moreover, when examined histologically, tumors from En/Erm-expressing animals show a trend toward greater stromal invasiveness. Detailed analysis of crypt-villus homeostasis in these En/Erm transgenic animals suggests increased epithelial turnover as one possible mechanism for the enhanced tumorigenesis. Our findings provide in vivo evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium

  8. Interleukin-6 Promotes Tumorigenesis by Altering DNA Methylation in Oral Cancer Cells

    OpenAIRE

    Gasche, Jacqueline A; Hoffmann, Jürgen; Boland, C. Richard; Goel, Ajay

    2011-01-01

    Worldwide oral squamous cell carcinoma (OSCC) accounts for more than 100,000 deaths each year. Chronic inflammation constitutes one of the key risk factors for OSCC. Accumulating evidence suggests that aberrant DNA methylation may contribute to OSCC tumorigenesis. This study investigated whether chronic inflammation alters DNA methylation and expression of cancer-associated genes in OSCC.

  9. Revelation 1:7 − A roadmap of God’s τέλοςfor his creation

    Directory of Open Access Journals (Sweden)

    Kobus de Smidt

    2013-11-01

    Full Text Available Revelation 1:7 points to an anticipated final appearance of Jesus at the consummation. This κηρύσσω developed from the late Jewish apocalyptic eschatology. This apocalyptic end time dawned with Jesus. The present time is thus simultaneously the end time, though the consummation is still in the future. As Jesus appeared on earth with his resurrection, so will he appear at the consummation − his resurrection appearance is a simile of his appearance at the consummation. He will appear in a corporeal form. The writer encourages the second-generation marginalised Christians. The Roman emperor is not the victor − Jesus is the axis mundi of God’s final purpose for his creation. The final appearance of Jesus will bring redemption for the believers and mourning for the unbelievers. The κηρύσσω of Revelation 1:7 is diametrically the opposite of the chiliasts. The country of Israel and her present inhabitants have no eschatological role to fulfil at the consummation. Openbaring 1:7 dui op ’n geantisipeerde finale verskyning van Jesus met die voleinding. Hierdie κηρύσσω het uit die Joodse laat-apokaliptiese eskatologie ontwikkel. Die apokaliptiese eindtyd het met Jesus se opstanding plaasgevind en die Nuwe-Testamentiese hede is dus alreeds die eindtyd. Die voleinding is egter nog in die toekoms. Jesus se verskyning met sy opstanding is ’n metafoor vir sy koms by die voleinding. Hy sal liggaamlik verskyn. Die skrywer bemoedig die gemarginaliseerde tweede generasie Christene. Die Romeinse keiser is nie die oorwinnaar nie − Jesus is die axis mundi van God se finale plan vir sy skepping. Die finale verskyning van Jesus sal vir die gelowiges ewige verlossing bewerk, maar die ongelowiges sal in rou gedompel word. Die κηρύσσω van Openbaring 1:7 is die teenoorgestelde van die standpunt van die chiliasme. Die land en huidige volk van Israel vervul geen eskatologiese rol by die voleinding nie.

  10. Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis.

    Science.gov (United States)

    Riku, Miho; Inaguma, Shingo; Ito, Hideaki; Tsunoda, Takumi; Ikeda, Hiroshi; Kasai, Kenji

    2016-02-01

    Although breast cancer is one of the most common malignancies, the molecular mechanisms underlying its development and progression are not fully understood. To identify key molecules involved, we screened publicly available microarray datasets for genes differentially expressed between breast cancers and normal mammary glands. We found that three of the genes predicted in this analysis were differentially expressed among human mammary tissues and cell lines. Of these genes, we focused on the role of the zinc-finger homeobox protein TSHZ2, which is down-regulated in breast cancer cells. We found that TSHZ2 is a nuclear protein harboring a bipartite nuclear localization signal, and we confirmed its function as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. Through comprehensive screening, we identified TSHZ2-suppressing genes such as AEBP1 and CXCR4, which are conversely up-regulated by GLI1, the downstream transcription factor of Hedgehog signaling. We found that GLI1 forms a ternary complex with CtBP2 in the presence of TSHZ2 and that the transcriptional activity of GLI1 is suppressed by TSHZ2 in a CtBP-dependent manner. Indeed, knockdown of TSHZ2 increases the expression of AEBP1 and CXCR4 in TSHZ2-expressing immortalized mammary duct epithelium. Concordantly, immunohistochemical staining of mammary glands revealed that normal duct cells expresses GLI1 in the nucleus along with TSHZ2 and CtBP2, whereas invasive ductal carcinoma cells, which does not express TSHZ2, show the increase in the expression of AEBP1 and CXCR4 and in the cytoplasmic localization of GLI1. Thus, we propose that down-regulation of TSHZ2 is crucial for mammary tumorigenesis via the activation of GLI1. PMID:26744317

  11. Correlation between Duffy blood group phenotype and breast cancer incidence

    International Nuclear Information System (INIS)

    Different ethnicities have different distribution of Duffy blood group (DBG) phenotypes and different breast cancer morbidity. A study in our lab demonstrated that Duffy antigen/receptor for chemokines (DARC, also known as DBGP, the Duffy protein phenotype), led to the inhibition of tumorigenesis. Therefore, we tested the hypothesis that DBGP is correlated with breast cancer occurrence. DBGP proteins were examined by indirect antiglobulin testing with anti-FYa and anti-FYb antibodies. The phenotypes were classified into four groups according to the agglutination reactions: FYa + FYb+, FYa + FYb-, FYa-FYb + and FYa-FYb-. The phenotypes and pathological diagnosis of consecutively hospitalized female patients (n = 5,022) suffering from breast cancer at the Shanghai Cancer Hospital and Henan Province Cancer Hospital were investigated. The relationships between DBGP expression with breast cancer occurrence, axillary lymph status, histological subtype, tumor size pathological grade and overall survival were analyzed. The incidence of breast cancer was significantly different between FYa + FYb + (29.8%), FYa + FYb- (33.2%), FYa-FYb + (45.6%) and FYa-FYb- (59.1%; P = 0.001). Significant different numbers of breast cancer patients had metastases to the axillary lymph nodes in the FYa + FYb + group (25.1%), FYa + FYb- (36.9%), FYa-FYb + (41.0%) and FYa-FYb- (50.0%, (P = 0.005). There was a statistical significance (p = 0.022) of the overall survival difference between patients with difference phenotypes. No significant difference was observed in cancer size (t-test, p > 0.05), histological cancer type (Fisher's exact test, p > 0.05) or histological grade (Fisher's exact test, p > 0.05) between every each DBGP group. DBGP is correlated with breast cancer incidence and axillary lymph node metastasis and overall survival. Further investigations are required to determine the underlying mechanism of Duffy blood group phenotype on breast cancer risk

  12. Correlation between Duffy blood group phenotype and breast cancer incidence

    Directory of Open Access Journals (Sweden)

    Liu Xiao-feng

    2012-08-01

    Full Text Available Abstract Background Different ethnicities have different distribution of Duffy blood group (DBG phenotypes and different breast cancer morbidity. A study in our lab demonstrated that Duffy antigen/receptor for chemokines (DARC, also known as DBGP, the Duffy protein phenotype, led to the inhibition of tumorigenesis. Therefore, we tested the hypothesis that DBGP is correlated with breast cancer occurrence. Methods DBGP proteins were examined by indirect antiglobulin testing with anti-FYa and anti-FYb antibodies. The phenotypes were classified into four groups according to the agglutination reactions: FYa + FYb+, FYa + FYb-, FYa-FYb + and FYa-FYb-. The phenotypes and pathological diagnosis of consecutively hospitalized female patients (n = 5,022 suffering from breast cancer at the Shanghai Cancer Hospital and Henan Province Cancer Hospital were investigated. The relationships between DBGP expression with breast cancer occurrence, axillary lymph status, histological subtype, tumor size pathological grade and overall survival were analyzed. Results The incidence of breast cancer was significantly different between FYa + FYb + (29.8%, FYa + FYb- (33.2%, FYa-FYb + (45.6% and FYa-FYb- (59.1%; P = 0.001. Significant different numbers of breast cancer patients had metastases to the axillary lymph nodes in the FYa + FYb + group (25.1%, FYa + FYb- (36.9%, FYa-FYb + (41.0% and FYa-FYb- (50.0%, (P = 0.005. There was a statistical significance (p = 0.022 of the overall survival difference between patients with difference phenotypes. No significant difference was observed in cancer size (t-test, p > 0.05, histological cancer type (Fisher's exact test, p > 0.05 or histological grade (Fisher's exact test, p > 0.05 between every each DBGP group. Conclusions DBGP is correlated with breast cancer incidence and axillary lymph node metastasis and overall survival. Further investigations are required to determine the underlying mechanism of Duffy blood group phenotype

  13. The conqueror motif in chapters 12-13: a heavenly and an earthly perspective in the Book of Revelation

    Directory of Open Access Journals (Sweden)

    EC Shin

    2007-09-01

    Full Text Available The theme of the conqueror motif in the book of Revelation is one of the prominent themes. The theme of the conqueror motif provides various symbolical messages from an exegetical and theological perspective. An alternative symbolic perspective provides a heavenly perspective and the symbolic transformation. Various images such as salvation for the conquerors and judgment of the evil ones, or victory of the Lamb and defeat of Satan, transform our earthly perspective into the heavenly perspective, and give us a new understanding as to how the conquerors should see the world. To provide the conquerors with a new understanding is to give them a reversed effect as a marginalized group and to reveal deep spiritual conflict between God and Satan. Who� is in control in history? With the result of the heavenly war between Michael and the dragon in 12:7-9, John proclaims the victory of God, who is the real conqueror, and provides the heavenly perspective that God is in control of the cosmos, as well as of history.

  14. Breast self-exam

    Science.gov (United States)

    Self-examination of the breast; BSE; Breast cancer - BSE; Breast cancer screening - self exam ... The best time to do a monthly self-breast exam is about 3 to 5 days after your period starts. Do it at the same time every month. Your breasts are ...

  15. P21-activated kinase 1 and breast cancer

    Institute of Scientific and Technical Information of China (English)

    Jun-Xiang Zhang; Da-Qiang Li; Rakesh Kumar

    2010-01-01

    @@ The p21 activated kinase 1 (PAK1) belongs to PAKs family, a group of highly evolutionarily conserved protein family of serine/threonine kinases, which acts as a downstream effector of the small GTPases Cdc42 and Rac1, firstly reported in 1994[1]. As a serine/threonine kinase, PAK1 plays an important role in many cellular functions including cell morphogenesis, motility, survival, mitosis, angiogenesis, and tumorigenesis. More than 40 proteins have been reported to be phosphorylated by PAK1[2]. Accumulating experimental data in multiple experimental systems provide compelling evidence that PAK1 plays an important role in breast cancer promotion and progression. PAK1 is overexpressed and/or hyperactivated in more than 50% of breast cancers[3]. On the other hand, PAK1 overexpression in estrogen receptor alpha (ER α) positive breast cancer is also closely associated with a reduced responsiveness to tamoxifen therapy[4]. Since PAK1 plays such a vital role in breast cancer, PAK1 targeted therapeutic approaches are likely to be useful in breast cancer treatment as well as in other human cancers with PAK1 upregulation and/or hyperactivation[5].

  16. Low expression of leptin and its association with breast cancer: A transcriptomic study.

    Science.gov (United States)

    Karim, Sajjad; Merdad, Adnan; Schulten, Hans-Juergen; Jayapal, Manikandan; Dallol, Ashraf; Buhmeida, Abdelbaset; Al-Thubaity, Fatima; Mirza, Zeenat; Gari, Mamdooh A; Chaudhary, Adeel G; Abuzenadah, Adel M; Al-Qahtani, Mohammed H

    2016-07-01

    The incidence of breast cancer is alarmingly increasing worldwide and also among Saudi women. Obesity is linked with an increased cancer risk and studies have also revealed that leptin may be involved in breast tumorigenesis particularly among obese women. Numerous transcriptomic studies have been carried out worldwide; however, molecular studies among breast cancer patients of diverse ethnic groups from the Arabian Peninsula are scarce. In the present study, whole transcriptome analysis of 45 surgically resected breast tumors from Saudi Arabian female patients was carried out. Expression data were analyzed, and molecular networks and canonical pathways were identified. We identified 1,159 differentially expressed genes using p-value with a false discovery rate 2 as a cut-off. Using ingenuity pathway analysis tool, we identified many canonical pathways that were implicated in breast cancer for the first time. Notably, along with other lipid metabolism molecules, leptin (LEP)was one of the most downregulated genes (fold cut-off, -7.03) with significant differences between the breast cancer and the control groups (pcancer from a Saudi female population revealed downregulation of LEP. Molecular pathway analysis demonstrated the role of LEP and other associated molecules of the lipid metabolism pathway. Involvement of leptin and lipid metabolism in breast cancer was highlighted. The majority of cases presented were of late stage, stressing the need to educate individuals concerning early diagnostic testing and the life-style risk factors for breast cancer such as unhealthy diet and obesity. PMID:27177292

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

    International Nuclear Information System (INIS)

    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

  18. Elevated expression of protein regulator of cytokinesis 1, involved in the growth of breast cancer cells.

    Science.gov (United States)

    Shimo, Arata; Nishidate, Toshihiko; Ohta, Tomohiko; Fukuda, Mamoru; Nakamura, Yusuke; Katagiri, Toyomasa

    2007-02-01

    To elucidate molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out a genome-wide expression profile analysis of 81 breast cancer cases by means of a combination of cDNA microarray and laser microbeam microdissection. Among the upregulated genes, we focused on the functional significance of protein regulator of cytokinesis 1 (PRC1) in the development of breast cancer. Western blot analysis using breast cancer cell lines revealed a significant increase in endogenous PRC1 levels in G(2)/M phase. Treatment of breast cancer cells with small interfering RNA against PRC1 effectively suppressed its expression and inhibited the growth of breast cancer cell lines T47D and HBC5. Furthermore, we found an interaction between PRC1 and kinesin family member 2C/mitotic centromere-associated kinesin (KIF2C/MCAK) by coimmunoprecipitation and immunoblotting using COS-7 cells, in which these molecules were introduced exogenously. These findings suggest the involvement of a PRC1-KIF2C/MCAK complex in breast tumorigenesis, and this complex should be a promising target for the development of novel treatments for breast cancer. PMID:17233835

  19. Breast autoaugmentation

    OpenAIRE

    Kirwan, Laurence

    2007-01-01

    A technique using a posteriorly based dermoglandular flap as an augmentation of the superior hemisphere of the breast combined with a periareolar mastopexy and vertical mastopexy is presented. The advantages of combining a periareolar mastopexy, in terms of reducing the length of the vertical scar and preventing areolar distortion, are explained.

  20. Breast Schwannoma

    OpenAIRE

    Neely Hines; Yihong Wang; Priscilla Slanetz; Vandana Dialani

    2011-01-01

    Schwannomas arise from Schwann cells of the peripheral nerve sheath. The most common locations include the head, neck, and extensor surfaces of the extremities. Intramammary schwannomas are very rare and account for only 2.6% of schwannomas. A review of the English literature reveals 27 such cases of breast schwannoma. In this paper we describe another such rare case.

  1. Breast cancer

    CERN Multimedia

    2002-01-01

    "Cancer specialists will soon be able to compare mammograms with computerized images of breast cancer from across Europe, in a bid to improve diagnosis and treatment....The new project, known as MammoGrid, brings together computer and medical imaging experts, cancer specialists, radiologists and epidemiologists from Bristol, Oxford, Cambridge, France and Italy" (1 page).

  2. The role of circadian rhythm in breast cancer

    Science.gov (United States)

    Li, Shujing; Ao, Xiang

    2013-01-01

    The circadian rhythm is an endogenous time keeping system shared by most organisms. The circadian clock is comprised of both peripheral oscillators in most organ tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the central nervous system. The circadian rhythm is crucial in maintaining the normal physiology of the organism including, but not limited to, cell proliferation, cell cycle progression, and cellular metabolism; whereas disruption of the circadian rhythm is closely related to multi-tumorigenesis. In the past several years, studies from different fields have revealed that the genetic or functional disruption of the molecular circadian rhythm has been found in various cancers, such as breast, prostate, and ovarian. In this review, we will investigate and present an overview of the current research on the influence of circadian rhythm regulating proteins on breast cancer. PMID:23997531

  3. Dichotomous roles for the orphan nuclear receptor NURR1 in breast cancer

    International Nuclear Information System (INIS)

    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

  4. Ultrasound-Guided Breast Biopsy

    Science.gov (United States)

    ... Professions Site Index A-Z Ultrasound-Guided Breast Biopsy An ultrasound-guided breast biopsy uses sound waves ... Guided Breast Biopsy? What is Ultrasound-Guided Breast Biopsy? Lumps or abnormalities in the breast are often ...

  5. Stereotactic (Mammographically Guided) Breast Biopsy

    Science.gov (United States)

    ... Resources Professions Site Index A-Z Stereotactic Breast Biopsy Stereotactic breast biopsy uses mammography – a specific type ... Breast Biopsy? What is Stereotactic (Mammographically Guided) Breast Biopsy? Lumps or abnormalities in the breast are often ...

  6. Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion

    OpenAIRE

    Xie Xiaofang; Wen Huiyan; Zhou Xiaoni; Feng Ping; Zhou Huiqin; Yang Huan; Shen Haiying; Zhu Xueming

    2010-01-01

    Abstract Background Tumor cell expression of Toll-like receptors (TLRs) can promote inflammation and cell survival in the tumor microenvironment. Toll-like receptor 4 (TLR4) signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. The expression of TLR4 in human breast cancer cell line MDA-MB-231 and its biological function in the development and progression of br...

  7. Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer

    International Nuclear Information System (INIS)

    Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth factor (EGF) receptor family are overexpressed in high percentages of human breast cancers. Because these molecules are plasma membrane-associated and involved in mitogenesis, it has been speculated that they function in concert with one another to promote breast cancer development and progression. Evidence to date supports a model wherein c-Src potentiates the survival, proliferation and tumorigenesis of EGF receptor family members, in part by associating with them. Phosphorylation of the EGF receptor by c-SRC is also critical for mitogenic signaling initiated by the EGF receptor itself, as well as by several G-protein coupled receptors (GPCRs), a cytokine receptor, and the estrogen receptor. Thus, c-Src appears to have pleiotropic effects on cancer cells by modulating the action of multiple growth-promoting receptors

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

    Science.gov (United States)

    Sun, Lin; Li, Yu; Yang, Bangxiang

    2016-09-01

    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. PMID:27166155

  9. 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 ...

  10. Breast cancer screenings

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000837.htm Breast cancer screenings To use the sharing features on this page, please enable JavaScript. Breast cancer screenings can help find breast cancer early, before ...

  11. Breast PET scan

    Science.gov (United States)

    Breast positron emission tomography; PET - breast; PET - tumor imaging - breast ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), usually ...

  12. 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. ...

  13. 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 ... usually aren't cancer. However, most men with breast cancer have lumps. Other breast symptoms can include Dimpled ...

  14. Breast reconstruction - implants

    Science.gov (United States)

    After a mastectomy , some women choose to have cosmetic surgery to remake their breast. This type of surgery ... to the breast or the new nipple. Having cosmetic surgery after breast cancer can improve your sense of ...

  15. MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1.

    Science.gov (United States)

    Jiang, Qian; He, Miao; Ma, Meng-Tao; Wu, Hui-Zhe; Yu, Zhao-Jin; Guan, Shu; Jiang, Long-Yang; Wang, Yan; Zheng, Da-Di; Jin, Feng; Wei, Min-Jie

    2016-03-01

    Wnt/β-catenin signaling pathway influences embryonic development, cell polarity and adhesion, apoptosis and tumorigenesis. MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. Taken together, our results suggest that miR-148a can suppress the migration and invasion of breast cancer cells by targeting WNT-1 and inhibiting Wnt/β-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis. PMID:26707142

  16. MiR-218 Mediates tumorigenesis and metastasis: Perspectives and implications

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Ying-fei [Institute Guangzhou of Advanced Technology, Chinese Academy of Sciences, Guangzhou (China); Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (China); Zhang, Li [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong (China); Waye, Mary Miu Yee [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Fu, Wei-ming, E-mail: wm.fu@giat.ac.cn [Institute Guangzhou of Advanced Technology, Chinese Academy of Sciences, Guangzhou (China); School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Zhang, Jin-fang, E-mail: zhangjf06@cuhk.edu.hk [Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (China); School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen (China)

    2015-05-15

    MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. As a highly conserved miRNA across a variety of species, microRNA-218 (miR-218) was found to play pivotal roles in tumorigenesis and progression. A group of evidence has demonstrated that miR-218 acts as a tumor suppressor by targeting many oncogenes related to proliferation, apoptosis and invasion. In this review, we provide a complex overview of miR-218, including its regulatory mechanisms, known functions in cancer and future challenges as a potential therapeutic target in human cancers. - Highlights: • miR-218 is frequently down regulated in multiple cancers. • miR-218 plays pivotal roles in carcinogenesis. • miR-218 mediates proliferation, apoptosis, metastasis, invasion, etc. • miR-218 mediates tumorigenesis and metastasis via multiple pathways.

  17. Long Telomeres Bypass the Requirement for Telomere Maintenance in Human Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Michael A.S. Taboski

    2012-02-01

    Full Text Available Despite the importance of telomere maintenance in cancer cell survival via the elongation of telomeres by telomerase reverse transcriptase (TERT or alternative lengthening of telomeres (ALT, it had not been tested directly whether telomere maintenance is dispensable for human tumorigenesis. We engineered human tumor cells containing loxP-flanked hTERT to enable extensive telomere elongation prior to complete hTERT excision. Despite unabated telomere erosion, hTERT-excised cells formed tumors in mice and proliferated in vitro for up to 1 year. Telomerase reactivation or ALT was not observed, and the eventual loss of telomeric signal coincided with loss of tumorigenic potential and cell viability. Crisis was averted via the reintroduction of active but not inactive hTERT. Thus, telomere maintenance is dispensable for human tumorigenesis when telomere reserves are long. Yet, despite telomere instability and the presence of oncogenic RAS, human tumors remain susceptible to crisis induced by critically short telomeres.

  18. An unregulated regulator: Vasa expression in the development of somatic cells and in tumorigenesis.

    Science.gov (United States)

    Poon, Jessica; Wessel, Gary M; Yajima, Mamiko

    2016-07-01

    Growing evidence in diverse organisms shows that genes originally thought to function uniquely in the germ line may also function in somatic cells, and in some cases even contribute to tumorigenesis. Here we review the somatic functions of Vasa, one of the most conserved "germ line" factors among metazoans. Vasa expression in somatic cells is tightly regulated and often transient during normal development, and appears to play essential roles in regulation of embryonic cells and regenerative tissues. Its dysregulation, however, is believed to be an important element of tumorigenic cell regulation. In this perspectives paper, we propose how some conserved functions of Vasa may be selected for somatic cell regulation, including its potential impact on efficient and localized translational activities and in some cases on cellular malfunctioning and tumorigenesis. PMID:27179696

  19. MiR-218 Mediates tumorigenesis and metastasis: Perspectives and implications

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. As a highly conserved miRNA across a variety of species, microRNA-218 (miR-218) was found to play pivotal roles in tumorigenesis and progression. A group of evidence has demonstrated that miR-218 acts as a tumor suppressor by targeting many oncogenes related to proliferation, apoptosis and invasion. In this review, we provide a complex overview of miR-218, including its regulatory mechanisms, known functions in cancer and future challenges as a potential therapeutic target in human cancers. - Highlights: • miR-218 is frequently down regulated in multiple cancers. • miR-218 plays pivotal roles in carcinogenesis. • miR-218 mediates proliferation, apoptosis, metastasis, invasion, etc. • miR-218 mediates tumorigenesis and metastasis via multiple pathways

  20. Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling

    OpenAIRE

    Britschgi, Adrian; Bill, Anke; Brinkhaus, Heike; Rothwell, Christopher; Clay, Ieuan; Duss, Stephan; Rebhan, Michael; Raman, Pichai; Guy, Chantale T.; Wetzel, Kristie; George, Elizabeth; Popa, M. Oana; Lilley, Sarah; Choudhury, Hedaythul; Gosling, Martin

    2013-01-01

    The calcium-activated chloride channel anoctamin 1 (ANO1) is located within the 11q13 amplicon, one of the most frequently amplified chromosomal regions in human cancer, but its functional role in tumorigenesis has remained unclear. The 11q13 region is amplified in ∼15% of breast cancers. Whether ANO1 is amplified in breast tumors, the extent to which gene amplification contributes to ANO1 overexpression, and whether overexpression of ANO1 is important for tumor maintenance have remained unkn...

  1. Control of cyclooxygenase-2 expression and tumorigenesis by endogenous 5-methoxytryptophan

    OpenAIRE

    Cheng, Huei-Hsuan; Kuo, Cheng-Chin; Yan, Jiann-Long; Chen, Hua-Ling; Lin, Wei-Chung; Wang, Kai-Hsuan; Tsai, Kelvin K.-C.; Guvén, Hayrettin; Flaberg, Emilie; Szekely, Laszlo; Klein, George; Wu, Kenneth K.

    2012-01-01

    Cyclooxygenase-2 (COX-2) expression is induced by mitogenic and proinflammatory factors. Its overexpression plays a causal role in inflammation and tumorigenesis. COX-2 expression is tightly regulated, but the mechanisms are largely unclear. Here we show the control of COX-2 expression by an endogenous tryptophan metabolite, 5-methoxytryptophan (5-MTP). By using comparative metabolomic analysis and enzyme-immunoassay, our results reveal that normal fibroblasts produce and release 5-MTP into t...

  2. Cancer stem cell immunology: key to understanding tumorigenesis and tumor immune escape?

    OpenAIRE

    Valentin eBruttel; Jörg eWischhusen

    2014-01-01

    Cancer stem cell (CSC) biology and tumor immunology have shaped our understanding of tumorigenesis. However, we still do not fully understand why tumors can be contained but not eliminated by the immune system and whether rare CSCs are required for tumor propagation.Long latency or recurrence periods have been described for most tumors. Conceptually, this requires a subset of malignant cells which is capable of initiating tumors, but is neither eliminated by immune cells nor able to grow stra...

  3. The heme–p53 interaction: Linking iron metabolism to p53 signaling and tumorigenesis

    OpenAIRE

    Shen, Jia; Sheng, Xiangpeng; Chang, ZeNan; Wu, Qian; Xie, Dong; Wang, Fudi; HU, Ronggui

    2014-01-01

    Recently, we reported that heme binds to tumor suppressor p53 protein (TP53, best known as p53) and promotes its nuclear export and cytosolic degradation, whereas iron chelation stabilizes p53 protein and suppresses tumors in a p53-dependent manner. This not only provides mechanistic insights into tumorigenesis associated with iron excess, but also helps guide the administration of chemotherapy based on iron deprivation in the clinic.

  4. Long Telomeres Bypass the Requirement for Telomere Maintenance in Human Tumorigenesis

    OpenAIRE

    Taboski, Michael A. S.; Sealey, David C.F.; Dorrens, Jennifer; Tayade, Chandrakant; Dean H Betts; Harrington, Lea

    2012-01-01

    Despite the importance of telomere maintenance in cancer cell survival via the elongation of telomeres by telomerase reverse transcriptase (TERT) or alternativelengthening of telomeres (ALT), it had not been tested directly whether telomere maintenance is dispensable for human tumorigenesis. We engineered human tumor cells containing loxP-flanked hTERT to enable extensive telomere elongation prior to complete hTERT excision. Despite unabated telomere erosion, hTERT-excised cells formed tumors...

  5. Transforming Growth Factor-Beta and Oxidative Stress Interplay: Implications in Tumorigenesis and Cancer Progression

    OpenAIRE

    2015-01-01

    Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-β and ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, ...

  6. Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine

    OpenAIRE

    Kim, Dong Hwan; Sung, Bokyung; Chung, Hae Young; Kim, Nam Deuk

    2014-01-01

    In this review, we will summarize the current understanding of modulation of colitis-associated colon tumorigenesis by two natural products, baicalein and betaine, which have anti-inflammatory activities. Baicalein and betaine have been shown to provide various health benefits to organism in many ways. Baicalein is a phenolic flavonoid derived originally from the root of Scutellaria baicalensis Georgi. From ancient times, baicalein has widely been used in oriental medicines as an anti-inflamm...

  7. ADAM17-mediated CD44 cleavage promotes orasphere formation or stemness and tumorigenesis in HNSCC

    International Nuclear Information System (INIS)

    CD44, an extracellular matrix (ECM) receptor, has been described as a cancer stem cell marker in multiple cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCC orasphere formation or stemness was characterized by cleavage of CD44, and thus we hypothesized that this proteolytic processing may be critical to stemness and tumorigenesis. We tested this hypothesis by examining the mechanisms that regulate this process in vitro and in vivo, and by exploring its clinical relevance in human specimens. Sphere assays have been used to evaluate stemness in vitro. Spheres comprised of HNSCC cells or oraspheres and an oral cancer mouse model were used to examine the significance of CD44 cleavage using stable suppression and inhibition approaches. These mechanisms were also examined in HNSCC specimens. Oraspheres exhibited increased levels of CD44 cleavage compared to their adherent counterparts. Given that disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) is a major matrix metalloproteinase known to cleave CD44, we chemically inhibited and stably suppressed ADAM17 expression in HNSCC cells and found that these treatments blocked CD44 cleavage and abrogated orasphere formation. Furthermore, stable suppression of ADAM17 in HNSCC cells also diminished tumorigenesis in an oral cancer mouse model. Consistently, stable suppression of CD44 in HNSCC cells abrogated orasphere formation and inhibited tumorigenesis in vivo. The clinical relevance of these findings was confirmed in matched primary and metastatic human HNSCC specimens, which exhibited increased levels of ADAM17 expression and concomitant CD44 cleavage compared to controls. CD44 cleavage by ADAM17 is critical to orasphere formation or stemness and HNSCC tumorigenesis

  8. Ras-Related Tumorigenesis Is Suppressed by BNIP3-Mediated Autophagy through Inhibition of Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Shan-Ying Wu

    2011-12-01

    Full Text Available Autophagy plays diverse roles in Ras-related tumorigenesis. H-rasval12 induces autophagy through multiple signaling pathways including Raf-1/ERK pathway, and various ERK downstream molecules of autophagy have been reported. In this study, Bcl-2/adenovirus E1B 19-kDa–interacting protein 3 (BNIP3 is identified as a downstream transducer of the Ras/Raf/ERK signaling pathway to induce autophagy. BNIP3 was upregulated by H-rasval12 at the transcriptional level to compete with Beclin 1 for binding with Bcl-2. H-rasval12–induced autophagy suppresses cell proliferation demonstrated both in vitro and in vivo by expression of ectopic BNIP3, Atg5, or interference RNA of BNIP3 (siBNIP3 and Atg5 (shAtg5 using mouse NIH3T3 and embryo fibroblast cells. H-rasval12 induces different autophagic responses depending on the duration of Ras overexpression. After a short time (48 hours of Ras overexpression, autophagy inhibits cell proliferation. In contrast, a longer time (2 weeks of Ras overexpression, cell proliferation was enhanced by autophagy. Furthermore, overexpression of mutant Ras, BNIP3, and LC3-II was detected in bladder cancer T24 cells and the tumor parts of 75% of bladder cancer specimens indicating a positive correlation between autophagy and tumorigenesis. Taken together, our mouse model demonstrates a balance between BNIP3-mediated autophagy and H-rasval12–induced tumor formation and reveals that H-rasval12 induces autophagy in a BNIP3-dependent manner, and the threshold of autophagy plays a decisive role in H-rasval12–induced tumorigenesis. Our findings combined with others’ reports suggest a new therapeutic strategy against Ras-related tumorigenesis by negative or positive regulation of autophagic activity, which is determined by the level of autophagy and tumor progression stages.

  9. Hypomethylation of Long Interspersed Nuclear Element-1 is Involved in the Early Tumorigenesis of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Wenhua Piao

    2014-08-01

    high FAL group. No associations between the level of hypomethylation of LINE-1 and HBV infection, age, sex, and cirrhosis were found. Conclusions: These results are strongly suggested that the hypomethylation of LINE-1 plays a role in the hepatocarcinogenesis; moreover, the hypomethylation of LINE-1 occurs not only in the progression of HCC, but also in the early stage of HCC tumorigenesis. [J Interdiscipl Histopathol 2014; 2(4.000: 191-196

  10. Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma

    OpenAIRE

    Li Xiangping; Weng Desheng; Wu Lirong; Li Gang; Wu Zhengrong; Yao Kaitai

    2009-01-01

    Abstract Background Human Cripto-1, a member of the EGF-CFC family, is indispensable for early embryonic development. Cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet little is known about Cripto-1 in nasopharyngeal carcinoma (NPC). The aim of this study was to analyze the roles of Cripto-1 in the progression and clinical characteristics in NPC clinical samples and cell lines. Methods The expression of Cripto-1 ...

  11. The role of the Akt/mTOR pathway in tobacco-carcinogen induced lung tumorigenesis

    OpenAIRE

    Memmott, Regan M.; Dennis, Phillip A.

    2009-01-01

    Lung cancer is the leading cause of cancer-related death in the United States, and 85–90% of lung cancer cases are associated with tobacco use. Tobacco components promote lung tumorigenesis through genotoxic effects, as well as through biochemical modulation of signaling pathways such as the Akt/mTOR pathway that regulate cell proliferation and survival. This review will describe cell surface receptors and other upstream components required for tobacco-carcinogen induced activation of Akt and...

  12. LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells

    OpenAIRE

    Wei, Qun; Chen, Zhenhua; Wang, Ling; Tong ZHANG; Duan, Lingling; Behrens, Carmen; Wistuba, Ignacio I.; Minna, John D.; Gao, Boning; Luo, Junhang; Liu, Zhi-Ping

    2015-01-01

    Lung cancer is the leading cause of cancer-related death in the United States and metastatic behavior is largely responsible for this mortality. Mutations in multiple “driver” oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor like 1 (LZTFL1) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previous...

  13. The telomere proteins in tumorigenesis and clinical outcomes of oral squamous cell carcinoma.

    Science.gov (United States)

    Benhamou, Y; Picco, V; Pagès, G

    2016-06-01

    The "Hallmarks of Cancer" describe the ways by which cancer cells bypass homeostasis. Escape from replicative senescence is one of the earliest features of cancer cells. Maintenance of the telomeres through reactivation of telomerase was initially associated with replicative immortality in various cancers. The shelterin complex, a telomeric hexaprotein association, plays a key role in telomere maintenance and in the hallmarks of cancer. Some shelterin proteins are overexpressed in diverse cancers and can promote tumorigenesis in animal models. Shelterin can also have an impact on tumor size, tumor growth and resistance to treatment. Studies into the expression level of shelterin in oral squamous cell carcinoma (OSCC) report contradictory results. Moreover, the exact role of these proteins in OSCC tumorigenesis remains uncertain. In this review, we examined the data linking telomeres and hallmarks of OSCC. Furthermore, we examined the literature concerning telomeres and the clinical outcome of OSCC. Finally, we propose a model encompassing the role of shelterin proteins in oral tumorigenesis and treatment outcome. PMID:27208844

  14. Extra sex combs, chromatin, and cancer: Exploring epigenetic regulation and tumorigenesis in Drosophila

    Institute of Scientific and Technical Information of China (English)

    Can Zhang; Bo Liu; Guangyao Li; Lei Zhou

    2011-01-01

    Developmental genetic studies in Drosophila unraveled the importance of Polycomb group (PcG) and Trithorax group (TrxG) genes in controlling cellular identity.PcG and TrxG proteins form histone modifying complexes that catalyze repressive or activating histone modifications,respectively,and thus maintaining the expression status of homeotic genes.Human orthologs of PcG and TrxG genes are implicated in tumorigenesis as well as in determining the prognosis of individual cancers.Recent whole genome analyses of cancers also highlighted the importance of histone modifying proteins in controlling tumorigenesis.Comprehensive understanding of the mechanistic relationship between histone regulation and tumorigenesis holds the promise of significantly advancing our understanding and management of cancer.It is anticipated that Drosophila melanogaster,the model organism that contributed significantly to our understanding of the functional role of histone regulation in development,could also provide unique insight for our understanding of how histone dysregulation can lead to cancer.In this review,we will discuss several recent advances in this regard.

  15. Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity

    Directory of Open Access Journals (Sweden)

    Wang Jufang

    2011-08-01

    Full Text Available Abstract Background Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that Atm/Brca1 double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in Atm and Brca1 heterozygosity. Methods Wild type cells, Atm or Brca1 single heterozygous cells, and Atm/Brca1 double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation. Results Remarkable high transformation frequency was confirmed in Atm/Brca1 double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways. Conclusions The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation.

  16. Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity

    International Nuclear Information System (INIS)

    Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that Atm/Brca1 double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in Atm and Brca1 heterozygosity. Wild type cells, Atm or Brca1 single heterozygous cells, and Atm/Brca1 double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation. Remarkable high transformation frequency was confirmed in Atm/Brca1 double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways. The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation

  17. PERK Activation Promotes Medulloblastoma Tumorigenesis by Attenuating Premalignant Granule Cell Precursor Apoptosis.

    Science.gov (United States)

    Ho, Yeung; Li, Xiting; Jamison, Stephanie; Harding, Heather P; McKinnon, Peter J; Ron, David; Lin, Wensheng

    2016-07-01

    Evidence suggests that activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress negatively or positively influences cell transformation by regulating apoptosis. Patched1 heterozygous deficient (Ptch1(+/-)) mice reproduce human Gorlin's syndrome and are regarded as the best animal model to study tumorigenesis of the sonic hedgehog subgroup of medulloblastomas. It is believed that medulloblastomas in Ptch1(+/-) mice results from the transformation of granule cell precursors (GCPs) in the developing cerebellum. Here, we determined the role of PERK signaling on medulloblastoma tumorigenesis by assessing its effects on premalignant GCPs and tumor cells. We found that PERK signaling was activated in both premalignant GCPs in young Ptch1(+/-) mice and medulloblastoma cells in adult mice. We demonstrated that PERK haploinsufficiency reduced the incidence of medulloblastomas in Ptch1(+/-) mice. Interestingly, PERK haploinsufficiency enhanced apoptosis of premalignant GCPs in young Ptch1(+/-) mice but had no significant effect on medulloblastoma cells in adult mice. Moreover, we showed that the PERK pathway was activated in medulloblastomas in humans. These results suggest that PERK signaling promotes medulloblastoma tumorigenesis by attenuating apoptosis of premalignant GCPs during the course of malignant transformation. PMID:27181404

  18. Breast imaging

    International Nuclear Information System (INIS)

    The majority of information available today indiates that the most efficient and accurate method of screening women to detect early-stage breast cancer is an aggressive program of patient self-examination, physical examination by well-trained, motivated personnel, and high-quality x-ray mammography. There are two important factors in the implementation of mammographic screening. The first is the availability of facilities to perform high-quality, low-dose mammography, which is directly related to the second factor: the expense to society for support of this large-scale effort. Cost-benefit analysis is beyond the scope of this review. In 1979 Moskowitz and Fox attempted to address this issue, using data from the Breast Cancer Detection Demonstration Project in Cincinnati, but additional analysis is required. The cost for each ''curable'' cancer that is detected must be compared with the psychological, social, and personal losses that accrue, as well as the numerous medical expenses incurred, in a frequently protracted death from breast cancer. All other imaging techniques that have been reviewed should be regarded as adjuncts to rather than replacements for mammographic screening. Ultrasound and computerized tomography are helpful when the physical examination and mammogram are equivocal. Other techniques, such as transillumination, thermography, and magnetic-resonance imaging, should be considered experimental. In patients with clinically evident lesions, x-ray mammography is helpful to evaluate the suspicious area, as well as to ''screen'' the remaining tissue in both breasts and to search for multicentric or bilateral lesions. Mammography is the only imaging technique that has been proved effective for screening

  19. Trianthema portulacastrum Linn. displays anti-inflammatory responses during chemically induced rat mammary tumorigenesis through simultaneous and differential regulation of NF-κB and Nrf2 signaling pathways.

    Science.gov (United States)

    Mandal, Animesh; Bishayee, Anupam

    2015-01-01

    Trianthema portulacastrum, a medicinal and dietary plant, has gained substantial importance due to its various pharmacological properties, including anti-inflammatory and anticarcinogenic activities. We have recently reported that a characterized T. portulacastrum extract (TPE) affords a considerable chemoprevention of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis though the underlying mechanisms are not completely understood. The objective of this study was to investigate anti-inflammatory mechanisms of TPE during DMBA mammary carcinogenesis in rats by monitoring cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-kappaB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Mammary tumors were harvested from our previous study in which TPE (50-200 mg/kg) was found to inhibit mammary tumorigenesis in a dose-response manner. The expressions of intratumor COX-2, HSP90, NF-κB, inhibitory kappaB-alpha (IκBα) and Nrf2 were determined by immunohistochemistry. TPE downregulated the expression of COX-2 and HSP90, blocked the degradation of IκBα, hampered the translocation of NF-κB from cytosol to nucleus and upregulated the expression and nuclear translocation of Nrf2 during DMBA mammary carcinogenesis. These results in conjunction with our previous findings suggest that TPE prevents DMBA-induced breast neoplasia by anti-inflammatory mechanisms mediated through simultaneous and differential modulation of two interconnected molecular circuits, namely NF-κB and Nrf2 signaling pathways. PMID:25622256

  20. Does tumorigenesis select for or against mutations of the DNA repair-associated genes BRCA2 and MRE11?: Considerations from somatic mutations in microsatellite unstable (MSI gastrointestinal cancers

    Directory of Open Access Journals (Sweden)

    Elghalbzouri-Maghrani Elhaam

    2006-01-01

    Full Text Available Abstract Background The BRCA2 and MRE11 proteins participate in the repair of double-strand DNA breaks by homologous recombination. Germline BRCA2 mutations predispose to ovarian, breast and pancreatic cancer, while a germline MRE11 mutation is associated with an ataxia telangiectasia-like disorder. Somatic mutations of BRCA2 are rare in typical sporadic cancers. In tumors having microsatellite instability (MSI, somatic truncating mutations in a poly [A] tract of BRCA2 are reported on occasion. Results We analyzed gastrointestinal MSI cancers by whole gene BRCA2 sequencing, finding heterozygous truncating mutations in seven (47% of 15 patients. There was no cellular functional defect in RAD51 focus-formation in three heterozygously mutated lines studied, although other potential functions of the BRCA2 protein could still be affected. A prior report of mutations in primary MSI tumors affecting the IVS5-(5–15 poly [T] tract of the MRE11 gene was confirmed and extended by analysis of the genomic sequence and protein expression in MSI cancer cell lines. Statistical analysis of the published MRE11 mutation rate in MSI tumors did not provide evidence for a selective pressure favoring biallelic mutations at this repeat. Conclusion Perhaps conflicting with common suspicions, the data are not compatible with selective pressures during tumorigenesis promoting the functional loss of BRCA2 and MRE11 in MSI tumors. Instead, these data fit closely with an absence of selective pressures acting on BRCA2 and MRE11 gene status during tumorigenesis.

  1. Breast Milk Best from the Breast?

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_159054.html Breast Milk Best From the Breast? Babies were more likely ... get ear infections if they were fed pumped milk, study found To use the sharing features on ...

  2. Breast Milk Best from the Breast?

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_159054.html Breast Milk Best From the Breast? Babies were more likely ... get ear infections if they were fed pumped milk, study found To use the sharing features on ...

  3. Establishment and characterization of two primary breast cancer cell lines from young Indian breast cancer patients: mutation analysis.

    Science.gov (United States)

    Pandrangi, Santhi Latha; Raju Bagadi, Sarangadhara Appala; Sinha, Navin Kumar; Kumar, Manoj; Dada, Rima; Lakhanpal, Meena; Soni, Abha; Malvia, Shreshtha; Simon, Sheeba; Chintamani, Chintamani; Mohil, Ravindar Singh; Bhatnagar, Dinesh; Saxena, Sunita

    2014-01-01

    Two novel triple negative breast cancer cell lines, NIPBC-1 and NIPBC-2 were successfully established from primary tumors of two young breast cancer patients aged 39 and 38 years respectively, diagnosed as infiltrating duct carcinoma of breast. Characterization of these cell lines showed luminal origin with expression of epithelial specific antigen and cytokeratin 18 and presence of microfilaments and secretary vesicles, microvilli, tight junctions and desmosomes on ultra-structural analysis. Both the cell lines showed anchorage independent growth and invasion of matrigel coated membranes. Karyotype analysis showed aneuploidy, deletions and multiple rearrangements in chromosomes 7, 9, X and 11 and isochromosomes 17q in both the cell lines. P53 mutational analysis revealed no mutation in the coding region in both the cell lines; however NIPBC-2 cell line showed presence of heterozygous C/G polymorphism, g.417 C > G (NM_000546.5) resulting in Arg/Pro allele at codon 72 of exon 4. Screening for mutations in BRCA1&2 genes revealed presence of three heterozygous polymorphisms in exon 11 of BRCA1 and 2 polymorphisms in exons 11, and14 of BRCA2 gene in both the cell lines. Both the cell lines showed presence of CD 44+/24-breast cancer stem cells and capability of producing mammosphere on culture. The two triple negative breast cancer cell lines established from early onset breast tumors can serve as novel invitro models to study mechanisms underlying breast tumorigenesis in younger age group patients and also identification of new therapeutic modalities targeting cancer stem cells. PMID:24502646

  4. Lentivirus-Mediated Knockdown of Myosin VI Inhibits Cell Proliferation of Breast Cancer Cell.

    Science.gov (United States)

    Wang, Hong; Wang, Biyun; Zhu, Wei; Yang, Ziang

    2015-10-01

    Myosin VI (MYO6) is a unique member of the myosin superfamily, and almost no experimental studies link MYO6 to tumorigenesis of breast cancer. However, previous microarray data demonstrated that MYO6 was frequently overexpressed in breast cancer tissues. In this study, to further develop its role in breast cancer, endogenous expression of MYO6 was significantly inhibited in breast cancer ZR-75-30 and MDA-MB-231 cells using lentivirus-mediated RNA interference. Quantitative polymerase chain reaction and western blot were applied to detect the expression level of MYO6. Cell viability of both cell lines was measured by methylthiazol tetrazolium and colony formation assays. Besides, cell cycle assay was utilized to acquire the distribution information of cell phase. The results demonstrated that knockdown of MYO6 markedly reduced cell viability and colony formation, as well as suppressed cell cycle progression in breast cancer cells. The results suggested that MYO6 played a vital role in breast cancer cells and might provide useful information for diagnosis and therapy of human breast cancer in future. PMID:26407123

  5. Attenuating Tumour Angiogenesis: A Preventive Role of Metformin against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Shan Gao

    2015-01-01

    Full Text Available Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive. In vivo assessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.

  6. Attenuating tumour angiogenesis: a preventive role of metformin against breast cancer.

    Science.gov (United States)

    Gao, Shan; Jiang, Jingcheng; Li, Pan; Song, Huijuan; Wang, Weiwei; Li, Chen; Kong, Deling

    2015-01-01

    Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive. In vivo assessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight) or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis. PMID:25883966

  7. Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas.

    Science.gov (United States)

    Ebbesen, Saya H; Scaltriti, Maurizio; Bialucha, Carl U; Morse, Natasha; Kastenhuber, Edward R; Wen, Hannah Y; Dow, Lukas E; Baselga, José; Lowe, Scott W

    2016-03-15

    Loss of the tumor suppressor gene PTEN is implicated in breast cancer progression and resistance to targeted therapies, and is thought to promote tumorigenesis by activating PI3K signaling. In a transgenic model of breast cancer, Pten suppression using a tetracycline-regulatable short hairpin (sh)RNA cooperates with human epidermal growth factor receptor 2 (HER2/neu), leading to aggressive and metastatic disease with elevated signaling through PI3K and, surprisingly, the mitogen-activated protein kinase (MAPK) pathway. Restoring Pten function is sufficient to down-regulate both PI3K and MAPK signaling and triggers dramatic tumor regression. Pharmacologic inhibition of MAPK signaling produces similar effects to Pten restoration, suggesting that the MAPK pathway contributes to the maintenance of advanced breast cancers harboring Pten loss. PMID:26929372

  8. Diagnostic and Therapeutic Implications of Histone Epigenetic Modulators in Breast Cancer.

    Science.gov (United States)

    Walsh, Louise; Gallagher, William M; O'Connor, Darran P; Ní Chonghaile, Tríona

    2016-05-01

    Breast cancer is the most common cancer in women and great advancements have been made for individualised patient treatment. Through understanding the underlying altered biology in the different subtypes of breast cancer, targeted therapeutics have been developed. Unfortunately, resistance to targeted therapy, intrinsic or acquired, is a recurring theme in cancer treatment. Epigenetic-mediated resistance to targeted therapy has been identified across different types of cancer. In addition, tumorigenesis has also been linked to altered expression of epigenetic modifiers. Due to the reversible nature of epigenetic modifications, epigenetic proteins are appealing as therapeutic targets in both the primary and relapsed/resistant setting. In this review, we will discuss the current state of targetable epigenetic histone modifications and their diagnostic and therapeutic implications in breast cancer. PMID:26895288

  9. 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 Overview Statistics Risk Factors and Prevention ...

  10. 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 is not clear. But there are risk ... breast cancer more likely in men: Exposure to radiation Higher ...

  11. Breast Cancer Overview

    Science.gov (United States)

    ... Other less common types of breast cancer include: Medullary Mucinous Tubular Metaplastic Papillary breast cancer Inflammatory breast cancer is a faster-growing type of cancer that accounts for about 1% to 5% of all breast cancers. Paget’s disease is a type of cancer that begins in ...

  12. Breast self-exam

    Science.gov (United States)

    A breast self-exam is a check-up a woman does at home to look for changes or problems in the breast tissue. ... not agree about the benefits of breast self-exams in finding breast cancer or saving lives. Talk ...

  13. Purinergic mechanisms in breast cancer support intravasation, extravasation and angiogenesis.

    Science.gov (United States)

    Buxton, Iain L O; Yokdang, Nucharee; Matz, Robert M

    2010-05-28

    Several advances have recently expanded models of tumor growth and promoted the concept of tumor homeostasis, the hypothesis that primary tumors exert an anti-proliferative effect on both themselves and subclinical secondary metastases. Recent trials indicate that the characterization of tumor growth as uncontrolled is inconsistent with animal models, clinical models, and epidemiological models. There is a growing body of evidence which lends support to an updated concept of tumor growth: tumor homeostasis. In the case of breast cancer, if not all metastasizing tumors, these advances suggest an inconvenient truth. That is, if breast tumor cells metastasize to distant sites early in the tumorigenesis process, then removal of a breast tumor may hasten the development of its metastases. We explore the heretofore unappreciated notion that nucleotides generated by tumor cells following the secretion of an ADP-kinase can promote metastasis and support angiogenesis. Evidence is presented that blockade of the actions of nucleotides in the setting of newly diagnosed breast cancer may provide a useful adjunct to current anti-angiogenesis treatment. PMID:19926395

  14. Breast cancer

    International Nuclear Information System (INIS)

    This book contains outstanding papers presented at the 3rd International Copenhagen Symposium on Detection of Breast Cancer, 1985. The Symposium was an opportunity to learn from extensive screening procedures carried out at outstanding centers in the United States, Sweden, the Netherlands, and England. Furthermore, the symposium dealt with new modalities such as ultrasonography, magnification techniques, and magnetic resonance; and very important contributions concerning self-examination, fine needle aspiration biopsy, and radiation risks were presented. A whole section was also dedicated to the highly important cooperation between radiologist, surgeon, and pathologist. (orig./MG)

  15. Activation of Akt1 accelerates carcinogen-induced tumorigenesis in mammary gland of virgin and post-lactating transgenic mice

    International Nuclear Information System (INIS)

    Data from in vivo and in vitro studies suggest that activation of Akt regulates cell survival signaling and plays a key role in tumorigenesis. Hence, transgenic mice were created to explore the oncogenic role of Akt1 in the development of mammary tumors. The transgenic mice were generated by expressing myristoylated-Akt1 (myr-Akt1) under the control of the MMTV-LTR promoter. The carcinogen 7, 12 dimethyl-1,2-benzanthracene (DMBA) was used to induce tumor formation. The MMTV driven myr-Akt1 transgene expression was detected primarily in the mammary glands, uterus, and ovaries. The expression level increased significantly in lactating mice, suggesting that the response was hormone dependent. The total Akt expression level in the mammary gland was also higher in the lactating mice. Interestingly, the expression of MMTVmyr-Akt1 in the ovaries of the transgenic mice caused significant increase in circulating estrogen levels, even at the post-lactation stage. Expression of myr-Akt1 in mammary glands alone did not increase the frequency of tumor formation. However, there was an increased susceptibility of forming mammary tumors induced by DMBA in the transgenic mice, especially in mice post-lactation. Within 34 weeks, DMBA induced mammary tumors in 42.9% of transgenic mice post-lactation, but not in wild-type mice post-lactation. The myr-Akt1 mammary tumors induced by DMBA had increased phosphorylated-Akt1 and showed strong expression of estrogen receptor (ERα) and epidermal growth factor receptor (EGFR). In addition, Cyclin D1 was more frequently up-regulated in mammary tumors from transgenic mice compared to tumors from wild-type mice. Overexpression of Cyclin D1, however, was not completely dependent on activated Akt1. Interestingly, mammary tumors that had metastasized to secondary sites had increased expression of Twist and Slug, but low expression of Cyclin D1. In summary, the MMTVmyr-Akt1 transgenic mouse model could be useful to study mechanisms of ER

  16. BREAST IMPLANT SURFACE DEVELOPMENT

    OpenAIRE

    Valencia Lazenco, Anai Alicia

    2015-01-01

    Bilateral breast augmentation is one of the most common cosmetic surgical procedures carried out on women in the western world. Breast augmentation involves increasing the volume of a woman‘s breasts through surgery by placing a silicone implant in the subglandular or subpectoral cavity. Although a capsule forms inevitably around breast implants as a natural part of healing, it can cause significant morbidity if the capsule becomes firm and contracted, a condition known as breast capsular con...

  17. Imaging male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, S., E-mail: sdoyle2@nhs.net [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom); Steel, J.; Porter, G. [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom)

    2011-11-15

    Male breast cancer is rare, with some pathological and radiological differences from female breast cancer. There is less familiarity with the imaging appearances of male breast cancer, due to its rarity and the more variable use of preoperative imaging. This review will illustrate the commonest imaging appearances of male breast cancer, with emphasis on differences from female breast cancer and potential pitfalls in diagnosis, based on a 10 year experience in our institution.

  18. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    Science.gov (United States)

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  19. Significance of β-tubulin Expression in Breast Premalignant Lesions and Carcinomas

    Institute of Scientific and Technical Information of China (English)

    Yuxia Gao; Yun Niu; Xiumin Ding; Yong Yu

    2008-01-01

    OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast, and to observe the relationship of its expression with breast cancer pathological features.METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast (ADH and Peri-PM with ADH), 50 specimens of breast in situ ductal carcinomas (DCIS), and 50 specimens of invasive ductal carcinomas (IDC). Thirty specimens of normal breast tissues served as a control group.RESULTS Immunohistochemical analysis showed that: the differences among the 4 groups (normal breast tissues, breast premalignant lesions, DCIS and IDC, P < 0.05) were significant,and there were also statistically significant differences between any 2 groups (P < 0.05) except for the β-tubulin positive expression comparing DCIS versus IDC (P > 0.05). In addition, β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH (P < 0.05). Following the degree of breast epithelial hyperplasia involved, and its development into carcinoma, the β-tubulin positive expression displayed an elevating tendency.We also found a significant positive relationship of β-tubulin expression with lymph node metastasis (P < 0.05), but no significant correlation with histological grading and nuclear grade.CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression. Studies of aberrations of centrosomal proteins provide a new way to explore the mechanism of breast tumorigenesis.

  20. Identification of Valid Reference Genes for the Normalization of RT-qPCR Expression Studies in Human Breast Cancer Cell Lines Treated with and without Transient Transfection

    OpenAIRE

    Liu, Lin-Lin; Zhao, Hui; Ma, Teng-Fei; Ge, Fei; Chen, Ce-Shi; Zhang, Ya-Ping

    2015-01-01

    Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is a powerful technique for examining gene expression changes during tumorigenesis. Target gene expression is generally normalized by a stably expressed endogenous reference gene; however, reference gene expression may differ among tissues under various circumstances. Because no valid reference genes have been documented for human breast cancer cell lines containing different cancer subtypes treated with transient transfec...

  1. Expression of protein tyrosine phosphatase alpha (RPTPalpha) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

    DEFF Research Database (Denmark)

    Ardini, E; Agresti, R; Tagliabue, E;

    2000-01-01

    Tyrosine phosphorylation is controlled by a balance of tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Whereas the contribution of PTKs to breast tumorigenesis is the subject of intense scrutiny, the potential role of PTPs is poorly known. RPTPalpha is implicated in the activati...... delayed tumor growth and metastasis. To our knowledge, this is the first example of a study correlating expression level of a specific bona fide PTP with neoplastic disease status in humans....

  2. HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity

    DEFF Research Database (Denmark)

    Fedele, Monica; Visone, Rosa; De Martino, Ivana;

    2006-01-01

    HMGA2 gene amplification and overexpression in human prolactinomas and the development of pituitary adenomas in HMGA2 transgenic mice showed that HMGA2 plays a crucial role in pituitary tumorigenesis. We have explored the pRB/E2F1 pathway to investigate the mechanism by which HMGA2 acts. Here we......2 mice. Thus, HMGA2-mediated E2F1 activation is a crucial event in the onset of these tumors in transgenic mice and probably also in human prolactinomas....

  3. Microarray gene expression analysis of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Meng Lian

    Full Text Available BACKGROUND: Laryngeal squamous cell carcinoma (LSCC is the most common type in head and neck squamous cell carcinoma (HNSCC, and the development and progression of LSCC are multistep processes accompanied by changes of molecular biology. OBJECTIVE: The purpose of this study was to investigate the molecular basis of tumorigenesis and regional lymph node metastasis in LSCC, and provide a set of genes that may be useful for the development of novel diagnostic markers and/or more effective therapeutic strategies. METHODS: A total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays, and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner. The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC. RESULTS: Analysed by Illumina mRNA microarrays, there were 361 genes significantly related to tumorigenesis while 246 genes significantly related to regional lymph node metastasis in LSCC. We found that the six genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4 were most frequently differently expressed functional genes related to tumorigenesis while eIF3a and RPN2 were most frequently differently expressed functional genes related to regional lymph node metastasis in LSCC. The expressions of these genes were also validated by qRT-PCR. CONCLUSIONS: The research revealed a gene expression signature of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma. Of the total, the deregulation of several genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4, EIF3a and RPN2 were potentially associated with disease development and progression. The result will contribute to the understanding of the

  4. Crosstalk between Desmoglein 2 and Patched 1 accelerates chemical-induced skin tumorigenesis

    OpenAIRE

    Brennan-Crispi, DM; Hossain, C; Sahu, J; Brady, M.; Riobo, NA; Mahoney, MG

    2015-01-01

    Aberrant activation of Hedgehog (Hh) signaling is causative of BCCs and has been associated with a fraction of SCCs. Desmoglein 2 (Dsg2) is an adhesion protein that is upregulated in many cancers and overexpression of Dsg2 in the epidermis renders mice more susceptible to squamous-derived neoplasia. Here we examined a potential crosstalk between Dsg2 and Hh signaling in skin tumorigenesis. Our findings show that Dsg2 modulates Gli1 expression, in vitro and in vivo. Ectopic expression of Dsg2 ...

  5. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.;

    2006-01-01

    culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... hierarchical positions along the retinoblastoma pathway. Our data provide new insights into oncogene-evoked DDR in human tumorigenesis, with potential implications for individualized management of tumors with elevated cyclin D1 versus cyclin E, due to their distinct clinical variables and biological behavior....

  6. Induction of persistent hypersensitivity to lung tumorigenesis by in utero X-radiation in mice

    International Nuclear Information System (INIS)

    A single dose (36 rad) of X rays was given to mouse embryos and neonates that were then treated with urethane at 21 days of age. Although in utero X-radiation to mice was not tumorigenic, it significantly increased lung tumor susceptibility to a postnatally-given carcinogen, urethane. X-ray induction of persistent hypersensitivity to lung tumorigenesis was apparent at all stages during days 0 to 14 of gestation (except on day 6), but was not observed at late fetal and neonatal stages

  7. Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis

    DEFF Research Database (Denmark)

    Bardi, G; Pandis, N; Fenger, C;

    1993-01-01

    Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural...... hyperplastic polyp. Both adenomas that had additional aberrations beyond the 1p loss showed severe dysplasia. We conclude that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis. The fact that the adenomas with 1p- as...

  8. Intestinal Peyer’s patches prevent tumorigenesis in Apc Min/+ mice

    OpenAIRE

    Fujimoto, Kyoko; Fujii, Gen; Sakurai, Hitomi; Yoshitome, Hiroko; Mutoh, Michihiro; Wada, Morimasa

    2014-01-01

    Peyer’s patches are nodules that play a central role in intestinal immunity. Few studies demonstrate the relationship between the number of Peyer’s patches and intestinal polyps. Here we identify a statistically significant inverse correlation between the quantity of Peyer’s patches and of the development of intestinal polyps in Apc Min/+ mice, which are a useful model to clarify the role of Peyer’s patches in intestinal tumorigenesis. Using this model, we increased the number of Peyer’s patc...

  9. MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis

    Science.gov (United States)

    Tomasetti, Marco; Amati, Monica; Santarelli, Lory; Neuzil, Jiri

    2016-01-01

    The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs). The interplay between oncogenic transformation-driven metabolic re-programming and modulation of aberrant miRNAs further established their critical role in the initiation, promotion and progression of cancer by creating a tumorigenesis-prone microenvironment, thus orchestrating processes of evasion to apoptosis, angiogenesis and invasion/migration, as well metastasis. Given the involvement of miRNAs in tumour development and their global deregulation, they may be perceived as biomarkers in cancer of therapeutic relevance. PMID:27213336

  10. MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Marco Tomasetti

    2016-05-01

    Full Text Available The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs. The interplay between oncogenic transformation-driven metabolic re-programming and modulation of aberrant miRNAs further established their critical role in the initiation, promotion and progression of cancer by creating a tumorigenesis-prone microenvironment, thus orchestrating processes of evasion to apoptosis, angiogenesis and invasion/migration, as well metastasis. Given the involvement of miRNAs in tumour development and their global deregulation, they may be perceived as biomarkers in cancer of therapeutic relevance.

  11. MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis.

    Science.gov (United States)

    Tomasetti, Marco; Amati, Monica; Santarelli, Lory; Neuzil, Jiri

    2016-01-01

    The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs). The interplay between oncogenic transformation-driven metabolic re-programming and modulation of aberrant miRNAs further established their critical role in the initiation, promotion and progression of cancer by creating a tumorigenesis-prone microenvironment, thus orchestrating processes of evasion to apoptosis, angiogenesis and invasion/migration, as well metastasis. Given the involvement of miRNAs in tumour development and their global deregulation, they may be perceived as biomarkers in cancer of therapeutic relevance. PMID:27213336

  12. Comparison of Clinicopathological Features and Treatments between Young (≤40 Years and Older (>40 Years Female Breast Cancer Patients in West China: A Retrospective, Epidemiological, Multicenter, Case Only Study.

    Directory of Open Access Journals (Sweden)

    Ke Wang

    Full Text Available The incidence of young cases of breast cancer is higher in China compared to the western world. We aimed to explore differences in risk factors, clinicopathological features and treatment modes of young female breast cancer compared to older patients in West China. We collected clinical information from 12,209 female breast cancer patients in West China, including risk factors, clinicopathological features and treatment modes, from January 2010 to December 2012. Chi-square tests and the multivariate logistic regression analysis were applied for statistical analysis. There were 2,682 young (≤40 years cases and 9,527 older cases at the time of breast cancer diagnosis. Young patients had a greater tumor diameter at diagnosis, and a higher probability of axillary lymph node and distant metastasis (P 40 years female breast cancer patients in West China. As some of these results differ from those found in the western female population, it is likely that the mechanism of tumorigenesis of young female breast cancer patients in West China may differ from that in western developed countries. Further investigation into the regional differences in breast cancer tumorigenesis is warranted.

  13. Breast metastases from rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Jia; FANG Yu; LI Ang; LI Fei

    2011-01-01

    Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

  14. Accelerated partial breast irradiation

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Whole breast radiotherapy afier tumor lumpectomy is based on the premise that that the breast cancer recurrence rate is reduced through the elimination of residual cancer foci in the remaining tissue immediately adjacent to the lumpectomy site and occult multicentric areas of in situ or infiltrating cancer in remote areas of the breast. The relevance of remote foci to ipsilateral breast failure rates after breast conserving treatment is debatable, because 65%~100% of recurrences develop in the same quadrant as the initial tumor. This has led several investigators to question whether radiotherapy must be administered to the entire breast.

  15. Delayed breast implant reconstruction

    DEFF Research Database (Denmark)

    Hvilsom, Gitte B.; Hölmich, Lisbet R.; Steding-Jessen, Marianne;

    2011-01-01

    -stage procedures. From the Danish Registry for Plastic Surgery of the Breast, which has prospectively registered data for women undergoing breast implantations since 1999, we identified 559 women without a history of radiation therapy undergoing 592 delayed breast reconstructions following breast cancer during the......Studies of complications following reconstructive surgery with implants among women with breast cancer are needed. As the, to our knowledge, first prospective long-term study we evaluated the occurrence of complications following delayed breast reconstruction separately for one- and two...

  16. GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity.

    Science.gov (United States)

    Louie, Sharon M; Grossman, Elizabeth A; Crawford, Lisa A; Ding, Lucky; Camarda, Roman; Huffman, Tucker R; Miyamoto, David K; Goga, Andrei; Weerapana, Eranthie; Nomura, Daniel K

    2016-05-19

    Breast cancers possess fundamentally altered metabolism that fuels their pathogenicity. While many metabolic drivers of breast cancers have been identified, the metabolic pathways that mediate breast cancer malignancy and poor prognosis are less well understood. Here, we used a reactivity-based chemoproteomic platform to profile metabolic enzymes that are enriched in breast cancer cell types linked to poor prognosis, including triple-negative breast cancer (TNBC) cells and breast cancer cells that have undergone an epithelial-mesenchymal transition-like state of heightened malignancy. We identified glutathione S-transferase Pi 1 (GSTP1) as a novel TNBC target that controls cancer pathogenicity by regulating glycolytic and lipid metabolism, energetics, and oncogenic signaling pathways through a protein interaction that activates glyceraldehyde-3-phosphate dehydrogenase activity. We show that genetic or pharmacological inactivation of GSTP1 impairs cell survival and tumorigenesis in TNBC cells. We put forth GSTP1 inhibitors as a novel therapeutic strategy for combatting TNBCs through impairing key cancer metabolism and signaling pathways. PMID:27185638

  17. Down-regulation of p73 correlates with high histological grade in Japanese with breast carcinomas

    Institute of Scientific and Technical Information of China (English)

    DU Cai-wen; Izo Kimijima; Toru Otake; Rikiya Abe; Seiichi Takenoshita; ZHANG Guo-jun

    2011-01-01

    Background p73, a homologue of p53, has been located at chromosome 1 p36-33, a region of frequently observed loss of heterozygosity in breast cancers. The objective of the present study was to investigate the function of p73 in Japanese with breast cancers. Methods Sixty Japanese patients with breast cancer were assessed by polymerase chain reaction single strand confirmation polymorphism analysis and direct sequencing to detect the p73 allele. p73 mRNA levels were also determined in 40 out of 60 patients by reverse-transcriptional polymerase chain reaction. Results We analyzed the entire open reading frame of the p73 gene by polymerase chain reaction single strand confirmation polymorphism and sequencing, and failed to identify any mutations of p73 in the encoding regions detected.Loss of heterozygosity of p73 was infrequent and only found in 9% of breast carcinomas. We revealed a few polymorphisms with a frequency of 13%-29%, which had been reported previously. Down-regulation of p73 mRNA expression was observed in tumor tissues in comparison to the normal breast tissues. A significant inverse correlation was found between p73 transcripts and high histological grade, suggesting that down-regulated p73 expression could be related to poor prognosis in those patients. Conclusion Our results suggest that p73 may serve as a tumor suppressor gene and its expression plays a role in tumorigenesis in Japanese patients with breast cancer.

  18. The progesterone receptor Val660→Leu polymorphism and breast cancer risk

    International Nuclear Information System (INIS)

    Recent evidence suggests a role for progesterone in breast cancer development and tumorigenesis. Progesterone exerts its effect on target cells by interacting with its receptor; thus, genetic variations, which might cause alterations in the biological function in the progesterone receptor (PGR), can potentially contribute to an individual's susceptibility to breast cancer. It has been reported that the PROGINS allele, which is in complete linkage disequilibrium with a missense substitution in exon 4 (G/T, valine→leucine, at codon 660), is associated with a decreased risk for breast cancer. Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 1252 cases and 1660 matched controls with the use of the Taqman assay. We did not observe any association of breast cancer risk with carrying the G/T (Val660→Leu) polymorphism (odds ratio 1.10, 95% confidence interval 0.93–1.30). In addition, we did not observe an interaction between this allele and menopausal status and family history of breast cancer as reported previously. Overall, our study does not support an association between the Val660→Leu PROGINS polymorphism and breast cancer risk

  19. Alterations in Circulating miRNA Levels following Early-Stage Estrogen Receptor-Positive Breast Cancer Resection in Post-Menopausal Women

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Zeuthen, Pernille; Binder, Harald; Knoop, Ann S; Ditzel, Henrik J

    2014-01-01

    alterations were also observed in an independent data set. METHODS: Global miRNA analysis was performed on prospectively collected serum samples from 24 post-menopausal women with estrogen receptor-positive early-stage breast cancer before surgery and 3 weeks after tumor resection using global LNA...... design and the same qPCR profiling platform, resulting in limited agreement. CONCLUSIONS: A panel of 4 circulating miRNAs exhibited significantly altered levels following radical resection of primary ER+ breast cancers in post-menopausal women. These specific miRNAs may be involved in tumorigenesis and...

  20. Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1

    International Nuclear Information System (INIS)

    Nisin, a bacteriocin and commonly used food preservative, may serve as a novel potential therapeutic for treating head and neck squamous cell carcinoma (HNSCC), as it induces preferential apoptosis, cell cycle arrest, and reduces cell proliferation in HNSCC cells, compared with primary keratinocytes. Nisin also reduces HNSCC tumorigenesis in vivo. Mechanistically, nisin exerts these effects on HNSCC, in part, through CHAC1, a proapoptotic cation transport regulator, and through a concomitant CHAC1-independent influx of extracellular calcium. In addition, although CHAC1 is known as an apoptotic mediator, its effects on cancer cell apoptosis have not been examined. Our studies are the first to report CHAC1's new role in promoting cancer cell apoptosis under nisin treatment. These data support the concept that nisin decreases HNSCC tumorigenesis in vitro and in vivo by inducing increased cell apoptosis and decreased cell proliferation; effects that are mediated by activation of CHAC1, increased calcium influxes, and induction of cell cycle arrest. These findings support the use of nisin as a potentially novel therapeutic for HNSCC, and as nisin is safe for human consumption and currently used in food preservation, its translation into a clinical setting may be facilitated

  1. Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1.

    Science.gov (United States)

    Joo, Nam E; Ritchie, Kathryn; Kamarajan, Pachiyappan; Miao, Di; Kapila, Yvonne L

    2012-12-01

    Nisin, a bacteriocin and commonly used food preservative, may serve as a novel potential therapeutic for treating head and neck squamous cell carcinoma (HNSCC), as it induces preferential apoptosis, cell cycle arrest, and reduces cell proliferation in HNSCC cells, compared with primary keratinocytes. Nisin also reduces HNSCC tumorigenesis in vivo. Mechanistically, nisin exerts these effects on HNSCC, in part, through CHAC1, a proapoptotic cation transport regulator, and through a concomitant CHAC1-independent influx of extracellular calcium. In addition, although CHAC1 is known as an apoptotic mediator, its effects on cancer cell apoptosis have not been examined. Our studies are the first to report CHAC1's new role in promoting cancer cell apoptosis under nisin treatment. These data support the concept that nisin decreases HNSCC tumorigenesis in vitro and in vivo by inducing increased cell apoptosis and decreased cell proliferation; effects that are mediated by activation of CHAC1, increased calcium influxes, and induction of cell cycle arrest. These findings support the use of nisin as a potentially novel therapeutic for HNSCC, and as nisin is safe for human consumption and currently used in food preservation, its translation into a clinical setting may be facilitated. PMID:23342279

  2. miR-92a family and their target genes in tumorigenesis and metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Molin, E-mail: molin_li@hotmail.com [Department of Pathophysiology, Basic Medical Science of Dalian Medical University, Dalian 116044 (China); Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian 116044 (China); Guan, Xingfang; Sun, Yuqiang [Department of Pathophysiology, Basic Medical Science of Dalian Medical University, Dalian 116044 (China); Mi, Jun [Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian 116044 (China); Shu, Xiaohong [College of Pharmacy, Dalian Medical University Cancer Center, Dalian 116044 (China); Liu, Fang [Department of Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027 (China); Li, Chuangang, E-mail: li_chuangang@sina.com [Department of Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027 (China)

    2014-04-15

    The miR-92a family, including miR-25, miR-92a-1, miR-92a-2 and miR-363, arises from three different paralog clusters miR-17-92, miR-106a-363, and miR-106b-25 that are highly conservative in the process of evolution, and it was thought as a group of microRNAs (miRNAs) correlated with endothelial cells. Aberrant expression of miR-92a family was detected in multiple cancers, and the disturbance of miR-92a family was related with tumorigenesis and tumor development. In this review, the progress on the relationship between miR-92a family and their target genes and malignant tumors will be summarized. - Highlights: • Aberrant expression of miR-92a, miR-25 and miR-363 can be observed in many kinds of malignant tumors. • The expression of miR-92a family is regulated by LOH, epigenetic alteration, transcriptional factors such as SP1, MYC, E2F, wild-type p53 etc. • Roles of miR-92a family in tumorigenesis and development: promoting cell proliferation, invasion and metastasis, inhibiting cell apoptosis.

  3. Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zane Linda

    2012-12-01

    Full Text Available Abstract Background Human T-cell Leukemia Virus type 1 (HTLV-1 infects 20 million individuals world-wide and causes Adult T-cell Leukemia/Lymphoma (ATLL, a highly aggressive T-cell cancer. ATLL is refractory to treatment with conventional chemotherapy and fewer than 10% of afflicted individuals survive more than 5 years after diagnosis. HTLV-1 encodes a viral oncoprotein, Tax, that functions in transforming virus-infected T-cells into leukemic cells. All ATLL cases are believed to have reduced p53 activity although only a minority of ATLLs have genetic mutations in their p53 gene. It has been suggested that p53 function is inactivated by the Tax protein. Results Using genetically altered mice, we report here that Tax expression does not achieve a functional equivalence of p53 inactivation as that seen with genetic mutation of p53 (i.e. a p53−/− genotype. Thus, we find statistically significant differences in tumorigenesis between Tax+p53+/+versus Tax+p53−/− mice. We also find a role contributed by the cellular Wip1 phosphatase protein in tumor formation in Tax transgenic mice. Notably, Tax+Wip1−/− mice show statistically significant reduced prevalence of tumorigenesis compared to Tax+Wip1+/+ counterparts. Conclusions Our findings provide new insights into contributions by p53 and Wip1 in the in vivo oncogenesis of Tax-induced tumors in mice.

  4. PLZF mediates the PTEN/AKT/FOXO3a signaling in suppression of prostate tumorigenesis.

    Directory of Open Access Journals (Sweden)

    JingPing Cao

    Full Text Available Promyelocytic leukemia zinc finger (PLZF protein expression is closely related to the progression of human cancers, including prostate cancer (PCa. However, the according context of a signaling pathway for PLZF to suppress prostate tumorigenesis remains greatly unknown. Here we report that PLZF is a downstream mediator of the PTEN signaling pathway in PCa. We found that PLZF expression is closely correlated with PTEN expression in a cohort of prostate cancer specimens. Interestingly, both PTEN rescue and phosphoinositide 3-kinase (PI3K inhibitor LY294002 treatment increase the PLZF expression in prostate cancer cell lines. Further, luciferase reporter assay and chromatin immunoprecipitation assay demonstrate that FOXO3a, a transcriptional factor phosphorylated by PI3K/AKT, could directly bind to the promoter of PLZF gene. These results indicate that PTEN regulates PLZF expression by AKT/FOXO3a. Moreover, our animal experiments also demonstrate that PLZF is capable of inhibiting prostate tumorigenesis in vivo. Taken together, our study defines a PTEN/PLZF pathway and would shed new lights for developing therapeutic strategy of prostate cancer.

  5. miR-92a family and their target genes in tumorigenesis and metastasis

    International Nuclear Information System (INIS)

    The miR-92a family, including miR-25, miR-92a-1, miR-92a-2 and miR-363, arises from three different paralog clusters miR-17-92, miR-106a-363, and miR-106b-25 that are highly conservative in the process of evolution, and it was thought as a group of microRNAs (miRNAs) correlated with endothelial cells. Aberrant expression of miR-92a family was detected in multiple cancers, and the disturbance of miR-92a family was related with tumorigenesis and tumor development. In this review, the progress on the relationship between miR-92a family and their target genes and malignant tumors will be summarized. - Highlights: • Aberrant expression of miR-92a, miR-25 and miR-363 can be observed in many kinds of malignant tumors. • The expression of miR-92a family is regulated by LOH, epigenetic alteration, transcriptional factors such as SP1, MYC, E2F, wild-type p53 etc. • Roles of miR-92a family in tumorigenesis and development: promoting cell proliferation, invasion and metastasis, inhibiting cell apoptosis

  6. Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine.

    Science.gov (United States)

    Kim, Dong Hwan; Sung, Bokyung; Chung, Hae Young; Kim, Nam Deuk

    2014-09-01

    In this review, we will summarize the current understanding of modulation of colitis-associated colon tumorigenesis by two natural products, baicalein and betaine, which have anti-inflammatory activities. Baicalein and betaine have been shown to provide various health benefits to organism in many ways. Baicalein is a phenolic flavonoid derived originally from the root of Scutellaria baicalensis Georgi. From ancient times, baicalein has widely been used in oriental medicines as an anti-inflammatory and anti-cancer therapy. Betaine, trimethylglycine, is an essential biochemical molecule of the methionine/homocysteine cycle and is synthesized by conversion of choline. Betaine is an important human nutrient obtained from various foods including sugar beet and lycium. Betaine has provided various health benefits including disease prevention. However, the action mechanisms of their activity remain poorly understood. Recent studies reported the effects of baicalein and betaine on cytotoxicity against colon cancer cells and chemically induced colitis-associated colon tumorigenesis in mice. Administrations of baicalein and betaine containing diets significantly inhibited the incidence of tumors and hyperplasia with down-regulation of inflammation. Therefore, baicalein and betaine might be applicable to the prevention of inflammation-associated colon carcinogenesis. PMID:25337584

  7. Loss of p53 Ser18 and Atm results in embryonic lethality without cooperation in tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Heather L Armata

    Full Text Available Phosphorylation at murine Serine 18 (human Serine 15 is a critical regulatory process for the tumor suppressor function of p53. p53Ser18 residue is a substrate for ataxia-telangiectasia mutated (ATM and ATM-related (ATR protein kinases. Studies of mice with a germ-line mutation that replaces Ser18 with Ala (p53(S18A mice have demonstrated that loss of phosphorylation of p53Ser18 leads to the development of tumors, including lymphomas, fibrosarcomas, leukemia and leiomyosarcomas. The predominant lymphoma is B-cell lymphoma, which is in contrast to the lymphomas observed in Atm(-/- animals. This observation and the fact that multiple kinases phosphorylate p53Ser18 suggest Atm-independent tumor suppressive functions of p53Ser18. Therefore, in order to examine p53Ser18 function in relationship to ATM, we analyzed the lifespan and tumorigenesis of mice with combined mutations in p53Ser18 and Atm. Surprisingly, we observed no cooperation in survival and tumorigenesis in compound p53(S18A and Atm(-/- animals. However, we observed embryonic lethality in the compound mutant animals. In addition, the homozygous p53Ser18 mutant allele impacted the weight of Atm(-/- animals. These studies examine the genetic interaction of p53Ser18 and Atm in vivo. Furthermore, these studies demonstrate a role of p53Ser18 in regulating embryonic survival and motor coordination.

  8. Breastfeeding and Breast Milk

    Science.gov (United States)

    ... Clinical Trials Resources and Publications Breastfeeding and Breast Milk: Condition Information Skip sharing on social media links Share this: Page Content Breastfeeding and Breast Milk: Condition Information​ ​​Breastfeeding, also called nursing, is the ...

  9. Breast reconstruction - natural tissue

    Science.gov (United States)

    ... scar One breast is larger than the other (asymmetry of the breasts) Loss of the flap because ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  10. Breast reconstruction - implants

    Science.gov (United States)

    ... One breast may be larger than the other (asymmetry of the breasts). You may have a loss ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  11. 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. ...

  12. Breast Reconstruction and Prosthesis

    Science.gov (United States)

    ... have breast reconstruction If you choose to have reconstructive surgery, follow these steps: STEP 1 — Ask your doctor to refer you to a plastic surgeon who is an expert in breast reconstruction. ...

  13. Breast Reconstruction After Mastectomy

    Science.gov (United States)

    ... reconstruction with or without radiotherapy. Current Opinion in Obstetrics and Gynecology 2011;23(1):44–50. [PubMed Abstract] Barry M, Kell MR. Radiotherapy and breast reconstruction: a meta-analysis. Breast ...

  14. Breast reconstruction - natural tissue

    Science.gov (United States)

    After a mastectomy , some women choose to have cosmetic surgery to remake their breast. This type of surgery ... Risks of anesthesia and surgery are: Reactions to medicines Breathing problems Bleeding, blood clots , or infection Risks of breast reconstruction with ...

  15. Types of Breast Cancers

    Science.gov (United States)

    ... about this condition, see Inflammatory Breast Cancer . Paget disease of the nipple This type of breast cancer ... carcinoma (this is a type of metaplastic carcinoma) Medullary carcinoma Mucinous (or colloid) carcinoma Papillary carcinoma Tubular ...

  16. Cosmetic breast surgery - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000273.htm Cosmetic breast surgery - discharge To use the sharing features on this page, please enable JavaScript. You had cosmetic breast surgery to change the size or shape ...

  17. miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4.

    Science.gov (United States)

    Zhao, Lifen; Feng, Xiaobin; Song, Xiaobo; Zhou, Huimin; Zhao, Yongfu; Cheng, Lei; Jia, Li

    2016-08-01

    Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR‑493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR‑493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer. PMID:27375041

  18. Breast Tissue Composition and Susceptibility to Breast Cancer

    OpenAIRE

    Boyd, Norman F.; Lisa J Martin; Bronskill, Michael; Martin J. Yaffe; Duric, Neb; Minkin, Salomon

    2010-01-01

    Breast density, as assessed by mammography, reflects breast tissue composition. Breast epithelium and stroma attenuate x-rays more than fat and thus appear light on mammograms while fat appears dark. In this review, we provide an overview of selected areas of current knowledge about the relationship between breast density and susceptibility to breast cancer. We review the evidence that breast density is a risk factor for breast cancer, the histological and other risk factors that are associat...

  19. Postreduction Breast Augmentation

    OpenAIRE

    Hidalgo, David A.; Doft, Melissa A.

    2015-01-01

    Background: Most breast reduction patients are highly satisfied after surgery. However, there is a subset of women who seek breast augmentation years later to restore lost volume chiefly associated with weight loss and postpartum changes. Breast shape and overall aesthetics are often revised at the same time. Methods: A retrospective review was performed of 2 surgeons’ experiences with post-reduction breast augmentation. Twenty patients were identified between 2002 and 2014. An in-depth chart...

  20. Breast Self- Examination Contradiction

    Directory of Open Access Journals (Sweden)

    Ayla Akkas Gursoy

    2008-06-01

    Full Text Available Breast cancer is very important health problem among women in the World and Turkey. Although treatment chance is very rising and survival is getting longer thanks to early diagnosis in breast cancer. Some discussion is making related to breast self examination which is one of the early detection methods in recent years. This article consider the discussions about breast self examination under the historical development light. [TAF Prev Med Bull 2008; 7(3.000: 257-260

  1. Stereotactic Image-Guided Navigation During Breast Reconstruction in Patients With Breast Cancer

    Science.gov (United States)

    2015-08-27

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  2. Breast lift (mastopexy) - slideshow

    Science.gov (United States)

    ... for drooping breasts, which may occur after a woman has had children. Mammograms (breast X-rays) and a routine breast exam are required before surgery. Update Date 2/12/2013 Updated by: David A. Lickstein, MD, FACS, specializing in cosmetic and reconstructive plastic surgery, Palm Beach Gardens, FL. ...

  3. Breast Cancer (For Kids)

    Science.gov (United States)

    ... With Breast Cancer Breast Cancer Prevention en español Cáncer de mama You may have heard about special events, like walks or races, to raise money for breast cancer research. Or maybe you've seen people wear ...

  4. Oncoplastic breast conserving surgery

    OpenAIRE

    Mansfield, Lucy; Agrawal, Avi; Cutress, Ramsey I.

    2013-01-01

    Oncoplastic breast conserving surgery is a fundamental component of the repertoire for the management of breast cancer. It facilitates removal of large volumes of breast tissue, and can improve cosmetic outcomes and patient satisfaction whilst maintaining good oncological principles, reducing re-excision and mastectomy rates and assisting in adjuvant radiotherapy planning.

  5. Do myoepithelial cells hold the key for breast tumorprogression?

    Energy Technology Data Exchange (ETDEWEB)

    Polyak, Kornelia; Hu, Min

    2005-11-18

    Mammary myoepithelial cells have been the foster child of breast cancer biology and have been largely ignored since they were considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge in stem cell biology and the cellular microenvironment has been increasing myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis if myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and if myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for cell cycle arrest, establishing epithelial cell polarity, and inhibiting migration and invasion. Based on these functions normal mammary myoepithelial cells have been called ''natural tumor suppressors''. However, during tumor progression myoepithelial cells seem to loose these properties and eventually they themselves diminish as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.

  6. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    Science.gov (United States)

    2016-02-18

    Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  7. ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumorigenesis

    Directory of Open Access Journals (Sweden)

    Campbell Craig I

    2010-09-01

    Full Text Available Abstract Background The type I insulin-like growth factor receptor (IGF-IR and ErbB2 (Her-2 are receptor tyrosine kinases implicated in human breast cancer. Both proteins are currently the subject of targeted therapeutics that are used in the treatment of breast cancer or which are in clinical trials. The focus of this study was to utilize our inducible model of IGF-IR overexpression to explore the interaction of these two potent oncogenes. Results ErbB2 was overexpressed in our RM11A cell line, a murine tumor cell line that overexpresses human IGF-IR in an inducible manner. ErbB2 conferred an accelerated tumor onset and increased tumor incidence after injection of RM11A cells into the mammary glands of syngeneic wild type mice. This was associated with increased proliferation immediately after tumor cell colonization of the mammary gland; however, this effect was lost after tumor establishment. ErbB2 overexpression also impaired the regression of established RM11A tumors following IGF-IR downregulation and enhanced their metastatic potential. Conclusion This study has revealed that even in the presence of vast IGF-IR overexpression, a modest increase in ErbB2 can augment tumor establishment in vivo, mediate resistance to IGF-IR downregulation and facilitate metastasis. This supports the growing evidence suggesting a possible advantage of using IGF-IR and ErbB2-directed therapies concurrently in the treatment of breast cancer.

  8. Models of breast cancer: quo vadis, animal modeling?

    International Nuclear Information System (INIS)

    Rodent models for breast cancer have for many decades provided unparalleled insights into cellular and molecular aspects of neoplastic transformation and tumorigenesis. Despite recent improvements in the fidelity of genetically engineered mice, rodent models are still being criticized by many colleagues for not being 'authentic' enough to the human disease. Motives for this criticism are manifold and range from a very general antipathy against the rodent model system to well-founded arguments that highlight physiological variations between species. Newly proposed differences in genetic pathways that cause cancer in humans and mice invigorated the ongoing discussion about the legitimacy of the murine system to model the human disease. The present commentary intends to stimulate a debate on this subject by providing the background about new developments in animal modeling, by disputing suggested limitations of genetically engineered mice, and by discussing improvements but also ambiguous expectations on the authenticity of xenograft models to faithfully mimic the human disease

  9. Inheritance of proliferative breast disease in breast cancer kindreds

    International Nuclear Information System (INIS)

    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

  10. Analysis and Revelation of Foreign Innovative Research Model%国外创新科研模式分析与启示

    Institute of Scientific and Technical Information of China (English)

    曾琪; 孙雪梅; 冀晓燕; 任雪勇

    2015-01-01

    文章分析了国外新型科研机构的运行模式和改革举措,列举了民间资本资助科学研究的案例,总结了国外创新科研模式的启示,探讨了我国科研机构如何在新形势下走出“创新”之路。%This paper analyzes the operating mode and the reform initiatives of overseas research institutions ,and cites the case of private capital to finance scientific research.Besides ,this paper also summarizes the revelation of foreign innovative research model,and explores the "innovation"road of Chinese research institutions in the new situation .

  11. 新加坡城市公共交通管理对广西的启示%Revelation of Singapore Urban Public Transport Management on Guangxi

    Institute of Scientific and Technical Information of China (English)

    陆正业

    2012-01-01

    文章从组织管理与规划管理两方面介绍了新加坡城市公共交通管理的成功经验,分析了该经验给广西城市公共交通管理所带来的启示,提出了广西城市公共交通的发展策略。%From two aspects of organizational management and planning management,t he article introduced the successful experience of urban public transport management in Singapore, analyzed the revelation of these experiences brought to urban public transport management in Guangxi, and proposed the development strategy of Guangxi urban public transport.

  12. Gossypiboma after Breast Augmentation

    OpenAIRE

    Kira Lundin; Allen, Julie E.; Lene Birk-Soerensen

    2013-01-01

    A 39-year-old woman was referred for removal of cosmetic breast implants and related siliconoma. After an exchange of breast implants at a private clinic a year previously, she had asymmetry of the right breast, persistent pain, and a generally unacceptable cosmetic result. An MRI had shown a well-defined area with spots of silicone-like material at the upper pole of the right breast. Surgical removal of presumed silicone-imbibed breast tissue was undertaken, and surprisingly a gossypiboma wa...

  13. Calcium sensing receptor suppresses human pancreatic tumorigenesis through a novel NCX1/Ca(2+)/β-catenin signaling pathway.

    Science.gov (United States)

    Tang, Bo; Chow, Jimmy Y C; Dong, Tobias Xiao; Yang, Shi-Ming; Lu, De-Sheng; Carethers, John M; Dong, Hui

    2016-07-10

    The calcium sensing receptor (CaSR) is functionally expressed in normal human pancreases, but its pathological role in pancreatic tumorigenesis is currently unknown. We sought to investigate the role of CaSR in pancreatic cancer (PC) and the underlying molecular mechanisms. We revealed that the expression of CaSR was consistently downregulated in the primary cancer tissues from PC patients, which was correlated with tumor size, differentiation and poor survival of the patients. CaSR activation markedly suppressed pancreatic tumorigenesis in vitro and in vivo likely through the Ca(2+) entry mode of Na(+)/Ca(2+) exchanger 1 (NCX1) to induce Ca(2+) entry into PC cells. Moreover, NCX1-mediated Ca(2+) entry resulted in Ca(2+)-dependent inhibition of β-catenin signaling in PC cells, eventually leading to the inhibition of pancreatic tumorigenesis. Collectively, we demonstrate for the first time that CaSR exerts a suppressive function in pancreatic tumorigenesis through a novel NCX1/Ca(2+)/β-catenin signaling pathway. Targeting this specific signaling pathway could be a potential therapeutic strategy for PC. PMID:27108064

  14. Early breast cancer

    International Nuclear Information System (INIS)

    Breast cancer remains a common disease throughout the world. Here we review new knowledge about early breast cancer obtained during the past 5 years. The prognosis of early breast cancer is generally favorable. Especially, ductal carcinoma in situ has been regarded as a non-life-threatening disease. Therefore, early diagnosis and early onset of the treatment has been important. Early age at menarche, late age at first birth, and late age at menopause are related to breast cancer risk. Examination by mammography and ultrasonography is still the most effective means of detection for premenopausal and postmenopausal women, respectively. Additionally, there have been important advances in MRI, sentinel lymph node biopsy, breast-conserving surgery, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant systemic therapy. Another approach to keeping the disease under control is the elucidation of breast cancer's molecular biological features. Assessment of potential molecular targets can lead to early diagnosis and molecular targeted treatment. (author)

  15. Brain diseases and tumorigenesis: The good and bad cops of pentraxin3.

    Science.gov (United States)

    Fornai, Francesco; Carrizzo, Albino; Ferrucci, Michela; Damato, Antonio; Biagioni, Francesca; Gaglione, Anderson; Puca, Annibale Alessandro; Vecchione, Carmine

    2015-12-01

    The prototype of long pentraxins, Pentraxin 3 (PTX3), is an evolutionarily conserved multifunctional, pattern-recognition protein constituted by a cyclic multimeric structure. PTX3 interacts with a variety of ligands, such as growth factors, extracellular matrix components, molecules of the complement cascade, pathogens recognition proteins, angiogenetic and adhesion molecules. PTX3 could be considered as a molecular link between innate and adaptive immunity as well as between focal and circulating responses during inflammation. In fact, it modulates the functions of resident dendritic cells and circulating lymphocytes. Recent evidence demonstrates that manipulation of PTX3 may produce even opposite effects depending on which target organ is considered and the physiopathological context. In the present review we discuss the good and bad cops of PTX3 concerning multifacted effects on inflammation, innate immunity, brain diseases and tumorigenesis. Finally, a perspective on PTX3 and autophagy is provided as a convergent pathway. PMID:26485684

  16. The Role of HPV in Head and Neck Cancer Stem Cell Formation and Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Mark S. Swanson

    2016-02-01

    Full Text Available The cancer stem cell (CSC theory proposes that a minority of tumor cells are capable of self-replication and tumorigenesis. It is these minority of cells that are responsible for cancer metastasis and recurrence in head and neck squamous cell cancers (HNSCC. Human papilloma virus (HPV-related cancer of the oropharynx is becoming more prevalent, which makes understanding of the relationship between HPV and CSCs more important than ever. This relationship is critical because CSC behavior can be predicted based on cell surface markers, which makes them a suitable candidate for targeted therapy. New therapies are an exciting opportunity to advance past the stalled outcomes in HNSCC that have plagued patients and clinicians for several decades.

  17. Wnt signaling and colon tumorigenesis — A view from the periphery

    International Nuclear Information System (INIS)

    In this brief overview we discuss the association between Wnt signaling and colon cell biology and tumorigenesis. Our current understanding of the role of Apc in the β-catenin destruction complex is compared with potential roles for Apc in cell adhesion and migration. The requirement for phosphorylation in the proteasomal-mediated degradation of β-catenin is contrasted with roles for phospho-β-catenin in the activation of transcription, cell adhesion and migration. The synergy between Myb and β-catenin regulation of transcription in crypt stem cells during Wnt signaling is discussed. Finally, potential effects of growth factor regulatory systems, Apc or truncated-Apc on crypt morphogenesis, stem cell localization and crypt fission are considered.

  18. Aberrant lysine acetylation in tumorigenesis: Implications in the development of therapeutics.

    Science.gov (United States)

    Kaypee, Stephanie; Sudarshan, Deepthi; Shanmugam, Muthu K; Mukherjee, Debanjan; Sethi, Gautam; Kundu, Tapas K

    2016-06-01

    The 'language' of covalent histone modifications translates environmental and cellular cues into gene expression. This vast array of post-translational modifications on histones are more than just covalent moieties added onto a protein, as they also form a platform on which crucial cellular signals are relayed. The reversible lysine acetylation has emerged as an important post-translational modification of both histone and non-histone proteins, dictating numerous epigenetic programs within a cell. Thus, understanding the complex biology of lysine acetylation and its regulators is essential for the development of epigenetic therapeutics. In this review, we will attempt to address the complexities of lysine acetylation in the context of tumorigenesis, their role in cancer progression and emphasize on the modalities developed to target lysine acetyltransferases towards cancer treatment. PMID:26808162

  19. 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

  20. ∆DNMT3B4-del Contributes to Aberrant DNA Methylation Patterns in Lung Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Mark Z. Ma

    2015-10-01

    Full Text Available Aberrant DNA methylation is a hallmark of cancer but mechanisms contributing to the abnormality remain elusive. We have previously shown that ∆DNMT3B is the predominantly expressed form of DNMT3B. In this study, we found that most of the lung cancer cell lines tested predominantly expressed DNMT3B isoforms without exons 21, 22 or both 21 and 22 (a region corresponding to the enzymatic domain of DNMT3B termed DNMT3B/∆DNMT3B-del. In normal bronchial epithelial cells, DNMT3B/ΔDNMT3B and DNMT3B/∆DNMT3B-del displayed equal levels of expression. In contrast, in patients with non-small cell lung cancer NSCLC, 111 (93% of the 119 tumors predominantly expressed DNMT3B/ΔDNMT3B-del, including 47 (39% tumors with no detectable DNMT3B/∆DNMT3B. Using a transgenic mouse model, we further demonstrated the biological impact of ∆DNMT3B4-del, the ∆DNMT3B-del isoform most abundantly expressed in NSCLC, in global DNA methylation patterns and lung tumorigenesis. Expression of ∆DNMT3B4-del in the mouse lungs resulted in an increased global DNA hypomethylation, focal DNA hypermethylation, epithelial hyperplastia and tumor formation when challenged with a tobacco carcinogen. Our results demonstrate ∆DNMT3B4-del as a critical factor in developing aberrant DNA methylation patterns during lung tumorigenesis and suggest that ∆DNMT3B4-del may be a target for lung cancer prevention.

  1. A Requirement for SOCS-1 and SOCS-3 Phosphorylation in Bcr-Abl-Induced Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Xiaoxue Qiu

    2012-06-01

    Full Text Available Suppressors of cytokine signaling 1 and 3 (SOCS-1 and SOCS-3 are inhibitors of the Janus tyrosine kinase (JAK/signal transducers and activators of transcription (STAT pathway and function in a negative feedback loop during cytokine signaling. Abl transformation is associated with constitutive activation of JAK/STAT-dependent signaling. However, the mechanism by which Abl oncoproteins bypass SOCS inhibitory regulation remains poorly defined. Here, we demonstrate that coexpression of Bcr-Abl with SOCS-1 or SOCS-3 results in tyrosine phosphorylation of these SOCS proteins. Interestingly, SOCS-1 is highly tyrosine phosphorylated in one of five primary chronic myelogenous leukemia samples. Bcr-Abl-dependent tyrosine phosphorylation of SOCS-1 and SOCS-3 occurs mainly on Tyr 155 and Tyr 204 residues of SOCS-1 and on Tyr 221 residue of SOCS-3. We observed that phosphorylation of these SOCS proteins was associated with their binding to Bcr-Abl. Bcr-Abl-dependent phosphorylation of SOCS-1 and SOCS-3 diminished their inhibitory effects on the activation of JAK and STAT5 and thereby enhanced JAK/STAT5 signaling. Strikingly, disrupting the tyrosine phosphorylation of SOCS-1 or SOCS-3 impaired the expression of Bcl-XL protein and sensitized K562 leukemic cells to undergo apoptosis. Moreover, selective mutation of tyrosine phosphorylation sites of SOCS-1 or SOCS-3 significantly blocked Bcr-Abl-mediated tumorigenesis in nude mice and inhibited Bcr-Abl-mediated murine bone marrow transformation. Together, these results reveal a mechanism of how Bcr-Abl may overcome SOCS-1 and SOCS-3 inhibition to constitutively activate the JAK/STAT-dependent signaling, and suggest that Bcr-Abl may critically requires tyrosine phosphorylation of SOCS-1 and SOCS-3 to mediate tumorigenesis when these SOCS proteins are present in cells.

  2. Corruption of homeostatic mechanisms in the guanylyl cyclase C signaling pathway underlying colorectal tumorigenesis

    Science.gov (United States)

    Waldman, Scott A

    2010-01-01

    Colon cancer, the second leading cause of cancer-related mortality worldwide, originates from the malignant transformation of intestinal epithelial cells. The intestinal epithelium undergoes a highly organized process of rapid regeneration along the crypt-villus axis, characterized by proliferation, migration, differentiation and apoptosis, whose coordination is essential to maintaining the mucosal barrier. Disruption of these homeostatic processes predisposes cells to mutations in tumor suppressors or oncogenes, whose dysfunction provides transformed cells an evolutionary growth advantage. While sequences of genetic mutations at different stages along the neoplastic continuum have been established, little is known of the events initiating tumorigenesis prior to adenomatous polyposis coli (APC) mutations. Here, we examine a role for the corruption of homeostasis induced by silencing novel tumor suppressors, including the intestine-specific transcription factor CDX2 and its gene target guanylyl cyclase C (GCC), as early events predisposing cells to mutations in APC and other sequential genes that initiate colorectal cancer. CDX2 and GCC maintain homeostatic regeneration in the intestine by restricting cell proliferation, promoting cell maturation and adhesion, regulating cell migration and defending the intestinal barrier and genomic integrity. Elimination of CDX2 or GCC promotes intestinal tumor initiation and growth in aged mice, mice carrying APC mutations or mice exposed to carcinogens. The roles of CDX2 and GCC in suppressing intestinal tumorigenesis, universal disruption in their signaling through silencing of hormones driving GCC, and the uniform overexpression of GCC by tumors underscore the potential value of oral replacement with GCC ligands as targeted prevention and therapy for colorectal cancer. PMID:20592492

  3. Deletion of Forkhead Box M1 transcription factor from respiratory epithelial cells inhibits pulmonary tumorigenesis.

    Directory of Open Access Journals (Sweden)

    I-Ching Wang

    Full Text Available The Forkhead Box m1 (Foxm1 protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1(-/- mice prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA/butylated hydroxytoluene (BHT. Decreased lung tumorigenesis in epFoxm1(-/- mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2alpha (TOPO-2alpha, a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2alpha mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2alpha promoter region, indicating that TOPO-2alpha is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2alpha expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy.

  4. Inhibition of induced tumorigenesis by dietary 2-deoxy-D-Glucose in mice

    International Nuclear Information System (INIS)

    Enhanced glycolysis facilitating proliferation and defence against death, besides energy production is a fundamental metabolic change exhibited by majority of the tumor types. Recent evidences support Warburg's proposition that this metabolic re-programming may also drive tumorigenesis induced by chemical carcinogens and radiation. Targeting this phenotype using the glycolytic inhibitor, 2-deoxy-D glucose (2-DG) has been shown to enhance the efficacy of radiation and chemotherapeutic drugs in experimental systems as well as clinics. 2-DG is also a potent Energy Restriction Mimetic Agent (ERMA) as an alternative to Dietary Energy Restriction (DER) for combating cancer. Since DER regimen is difficult to sustain in humans, we have hypothesized that 2-DG may impair the process of induced tumorigenesis, thereby offering an attractive chemopreventive strategy. Systematic studies have indeed shown that dietary 2-DG administration impairs the formation and growth of implanted tumor (Lewis Lung carcinoma; Ehrlich ascites carcinoma) as well as chemical (DMBA and TPA) and radiation-induced skin tumors in C57BL/6, Strain A and Swiss Albino mice respectively in the tumor implant study. Decrease in the fraction of animals bearing tumor and growth rate, besides increase in the latency period were evident. In the chemical and radiation induced tumor studies, a significant reduction in the percentage of tumor (papillomas) bearing animals (incidence), number of tumors per animal (tumor burden) and increased latency were observed. Although, mechanisms underlying cancer preventive/inhibitory potential of dietary 2-DG is not completely understood, our current findings suggests modifications of certain circulating factors (glucose and insulin), oxidative stress (LPO and GSH), immune status (CD4/CD8 and regulatory T-cells; T-regs), extracellular matrix (MMP-9) and angiogenesis (tumor associated and radiation-induced) as some of the contributing factors. Further studies are required

  5. FHL2 silencing reduces Wnt signaling and osteosarcoma tumorigenesis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Julia Brun

    Full Text Available BACKGROUND: The molecular mechanisms that are involved in the growth and invasiveness of osteosarcoma, an aggressive and invasive primary bone tumor, are not fully understood. The transcriptional co-factor FHL2 (four and a half LIM domains protein 2 acts as an oncoprotein or as a tumor suppressor depending on the tissue context. In this study, we investigated the role of FHL2 in tumorigenesis in osteosarcoma model. METHODOLOGY/PRINCIPAL FINDINGS: Western blot analyses showed that FHL2 is expressed above normal in most human and murine osteosarcoma cells. Tissue microarray analysis revealed that FHL2 protein expression is high in human osteosarcoma and correlates with osteosarcoma aggressiveness. In murine osteosarcoma cells, FHL2 silencing using shRNA decreased canonical Wnt/β-catenin signaling and reduced the expression of Wnt responsive genes as well as of the key Wnt molecules Wnt5a and Wnt10b. This effect resulted in inhibition of osteosarcoma cell proliferation, invasion and migration in vitro. Using xenograft experiments, we showed that FHL2 silencing markedly reduced tumor growth and lung metastasis occurence in mice. The anti-oncogenic effect of FHL2 silencing in vivo was associated with reduced cell proliferation and decreased Wnt signaling in the tumors. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that FHL2 acts as an oncogene in osteosarcoma cells and contributes to tumorigenesis through Wnt signaling. More importantly, FHL2 depletion greatly reduces tumor cell growth and metastasis, which raises the potential therapeutic interest of targeting FHL2 to efficiently impact primary bone tumors.

  6. The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Shao-wu ZOU; Kai-xing AI; Zhi-gang WANG; Zhou YUAN; Jun YAN; Qi ZHENG

    2011-01-01

    Aim: To explore the role of Med19, a component of the Mediator complex that coactivates DNA-binding transcription factors, in the proliferation and tumorigenesis of human hepatocellular carcinoma cells.Methods: The human hepatocellular carcinoma cell lines HepG2 and Hep3B were infected with lentiviral vectors encoding interfering RNA (RNAi) targeting the Med19 gene. To further confirm the inhibitory effects of RNAi vectors on Med19 gene expression, quantitative real-time RT-PCR and Western blotting assays were used. The proliferation of HepG2 and Hep3B cells after transduction with the Med19-RNAi-Lentivirus vector was evaluated by MTT conversion, BrdU incorporation, colony formation, and cell-cycle assays in vitro.In addition, the ability of the Med19-RNAi-Lentivirus vector-infected Hep3B cells to form tumors after inoculation into nude mice was determined.Results: Recombinant lentiviral vectors expressing small interfering RNA (siRNA) against Med19 were constructed and were found to efficiently downregulate Med19 mRNA and protein levels in HepG2 and Hep3B cells. Furthermore, the inhibition of Med19 by RNAi dramatically reduced hepatocellular carcinoma cell proliferation, induced cell-cycle arrest in the G0/G1 phase, and suppressed tumor formation.Conclusion: These results provide new evidence of an important role for Med19 in the development of hepatocellular carcinomas, suggesting that lentivirus-mediated RNAi to target Med19 is a potential tool for inhibiting cancer cell proliferation and tumorigenesis.

  7. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lin Yang; Li-Ge Kuang; Hua-Chuan Zheng; Jin-Yi Li; Dong-Ying Wu; Su-Min Zhang; Yan Xin

    2003-01-01

    AIM: To detect the expression of PTEN encoding productin normal mucosa, intestinal metaplasia (IM), dysplasia andcarcinoma of the stomach, and to investigate its clinicalimplication in tumorigenesis and progression of gastriccarcinoma.METHODS: Formalin-fixed paraffin embedded specimens from184 cases of gastric carcinoma, their adjacent normal mucosa,IM and dysplasia were evaluated for PTEN protein expressionby SABC immunohistochemistry. PTEN expression wascompared with tumor stage, lymph node metastasis, Lauren'sand WHO's histological classification of gastric carcinoma.Expression of VEGF was also detected in 60 cases of gastriccarcinoma and its correlation with PTEN was concerned.RESULTS: The positive rates of PTEN protein were 100 %(102/102), 98.5 %(65/66), 66.7 % (4/6) and 47.8 %(88/184)in normal mucosa, IM, dysplasia and carcinoma of the stomach,respectively. The positive rates in dysplasia and carcinomawere lower than in normal mucosa and IM (P<0.01).Advanced gastric cancers expressed less frequent PTEN thanearly gastric cancer (42.9 % v567.6 %, P<0.01). The positiverate of PTEN protein was lower in gastric cancer with thanwithout lymph node metastasis (40.3 % v563.3 %, P<0.01).PTEN was less expressed in diffuse-type than in intestinal-type gastric cancer (41.5 % v557.8 %,P<0.05). Signet ringcell carcinoma showed the expression of PTEN at the lowestlevel (25.0 %, 7/28); less than well and moderatelydifferentiated ones (P<0.01). Expression of PTEN was notcorrelated with expression of VEGF (P>0.05).CONCLUSION: Loss or reduced expression of PTEN proteinoccures commonly in tumorigenesis and progression of gastriccarcinoma. It is suggested that PTEN can be an objective markerfor pathologically biological behaviors of gastric carcinoma.

  8. Mdm2 Deficiency Suppresses MYCN-Driven Neuroblastoma Tumorigenesis In Vivo

    Directory of Open Access Journals (Sweden)

    Zaowen Chen

    2009-08-01

    Full Text Available Neuroblastoma is derived from neural crest precursor components of the peripheral sympathetic nervous system and accounts for more than 15% of all pediatric cancer deaths. A clearer understanding of the molecular basis of neuroblastoma is required for novel therapeutic approaches to improve morbidity and mortality. Neuroblastoma is uniformly p53 wild type at diagnosis and must overcome p53-mediated tumor suppression during pathogenesis. Amplification of the MYCN oncogene correlates with the most clinically aggressive form of the cancer, and MDM2, a primary inhibitor of the p53 tumor suppressor, is a direct transcriptional target of, and positively regulated by, both MYCN and MYCC. We hypothesize that MDM2 contributes to MYCN-driven tumorigenesis helping to ameliorate p53-dependent apoptotic oncogenic stress during tumor initiation and progression. To study the interaction of MYCN and MDM2, we generated an Mdm2 haploinsufficient transgenic animal model of neuroblastoma. In Mdm2+/-MYCN transgenics, tumor latency and animal survival are remarkably extended, whereas tumor incidence and growth are reduced. Analysis of the Mdm2/p53 pathway reveals remarkable p53 stabilization counterbalanced by epigenetic silencing of the p19Arf gene in the Mdm2 haploinsufficient tumors. In human neuroblastoma xenograft models, conditional small interfering RNA-mediated knockdown of MDM2 in cells expressing wild-type p53 dramatically suppresses tumor growth in a p53-dependent manner. In summary, we provided evidence for a crucial role for direct inhibition of p53 by MDM2 and suppression of the p19ARF/p53 axis in neuroblastoma tumorigenesis, supporting the development of therapies targeting these pathways.

  9. Suppression of intracranial glioma tumorigenesis with vascular endothelial growth factor antisense oligonucleotide in rats

    Institute of Scientific and Technical Information of China (English)

    李维方; 张光霁; 朱诚; 金由辛; 卢亦成

    2003-01-01

    Objective: To observe the inhibition of intracranial glioma tumorigenesis by vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide (ODN) in rats. Methods: Totally 20 μl Hank's liquid containing 1×106 C6 glioma cells was seeded into rat right caudate putamen in high-flow microinfusion with stereotactic technique. VEGF antisense ODN was simultaneously used with glioma cell. Each rat of the treated groupⅠ and the treated group Ⅱ was treated with 1 000 μmol/L VEGF antisense ODN. Each rat of the treated group Ⅲ and the treated group Ⅳ was treated with 2 000 μmol/L VEGF antisense ODN. The experimental periods of the treated group Ⅰ, the treated group Ⅲ and the control group Ⅰ were 2 weeks, those of the treated group Ⅱ, the treated group Ⅳ and the control group Ⅱ were 3 weeks. Before sacrifice, MRI was performed on each rat. Tumor magnitude and pathologic examination were detected after samples were dissected. Results: The survival state of all treated rats was better, and that of the control rats was in severe danger. The tumor volumes of the treated group Ⅰ and the treated group Ⅱ were remarkably lessened. Tumor tissue could not be found macroscopically in the brain samples of the treated group Ⅲ and the treated group Ⅳ, but tumor nest could be found with microscopy. Tumors of the treated groupⅠand the treated group Ⅱ had weak expressions of VEGF mRNA and VEGF, while normal brains and the samples of the treated group Ⅲ and the treated group Ⅳ had negative expressions, but tumors of the control groups had strong expressions. Conclusion: VEGF antisense ODN used early in situ can suppress angiogenesis and growth of rat intracranial glioma to retard tumorigenesis.

  10. Dose and Spatial Effects in Long-Distance Radiation Signaling In Vivo: Implications for Abscopal Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Mancuso, Mariateresa, E-mail: mariateresa.mancuso@enea.it [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA) Centro Ricerche Casaccia, Rome (Italy); Giardullo, Paola [Guglielmo Marconi University, Rome (Italy); Leonardi, Simona [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA) Centro Ricerche Casaccia, Rome (Italy); Pasquali, Emanuela [Guglielmo Marconi University, Rome (Italy); Casciati, Arianna [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA) Centro Ricerche Casaccia, Rome (Italy); De Stefano, Ilaria [Guglielmo Marconi University, Rome (Italy); Tanori, Mirella; Pazzaglia, Simonetta [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA) Centro Ricerche Casaccia, Rome (Italy); Saran, Anna, E-mail: anna.saran@enea.it [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA) Centro Ricerche Casaccia, Rome (Italy)

    2013-03-01

    Purpose: To investigate the dose and spatial dependence of abscopal radiation effects occurring in vivo in the mouse, along with their tumorigenic potential in the central nervous system (CNS) of a radiosensitive mouse model. Methods and Materials: Patched1 (Ptch1){sup +/−} mice, carrying a germ-line heterozygous inactivating mutation in the Ptch1 gene and uniquely susceptible to radiation damage in neonatal cerebellum, were exposed directly to ionizing radiation (1, 2, or 3 Gy of x-rays) or treated in a variety of partial-body irradiation protocols, in which the animals' head was fully protected by suitable lead cylinders while the rest of the body was exposed to x-rays in full or in part. Apoptotic cell death was measured in directly irradiated and shielded cerebellum shortly after irradiation, and tumor development was monitored in lifetime groups. The same endpoints were measured using different shielding geometries in mice irradiated with 3 or 10 Gy of x-rays. Results: Although dose-dependent cell death was observed in off-target cerebellum for all doses and shielding conditions tested, a conspicuous lack of abscopal response for CNS tumorigenesis was evident at the lowest dose of 1 Gy. By changing the amount of exposed body volume, the shielding geometry could also significantly modulate tumorigenesis depending on dose. Conclusions: We conclude that interplay between radiation dose and exposed tissue volume plays a critical role in nontargeted effects occurring in mouse CNS under conditions relevant to humans. These findings may help understanding the mechanisms of long-range radiation signaling in harmful effects, including carcinogenesis, occurring in off-target tissues.

  11. Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Wei Song; Jiguang Wang; Ying Yang; Naihe Jing; Xiangsun Zhang; Luonan Chen; Jiarui Wu

    2012-01-01

    Many of oncogenes and tumor suppressor genes have been found to exert variable and even opposing roles in different kinds of tumors or at different stages of cancer development.Here we showed that tumorigenic potential of mouse embryonic carcinoma P19 cells cultured in adherent plates (attached-P19-cells) was suppressed by a chemotherapeutic agent,5-aza-2'-deoxycytidine (ZdCyd),whereas the higher pro-tumorigenicity of P19 cells growing in suspension (detached-P19-cells) was generated by the ZdCyd treatment.Surprisingly,p53 activity was highly up-regulated by ZdCyd in both growing conditions.By our developed computational approaches,we revealed that there was a significant enrichment of apoptotic pathways in the ZdCyd-induced p53-dominant gene-regulatory network in attached P19 cells,whereas the pro-survival genes were significantly enriched in the ZdCyd-induced p53 network in detached P19 cells.The protein-protein interaction network of the ZdCyd-treated detached P19 cells was significantly different from that of ZdCyd-treated attached P19 cells.On the other hand,inhibition of pS3 expression by siRNA suppressed the ZdCyd-induced tumorigenesis of detached P19 cells,suggesting that the ZdCyd-activated p53 plays oncogenic function in detached P19 cells.Taken together,these results indicate a context-dependent role for the ZdCyd-activated p53-dominant network in tumorigenesis.

  12. Germline Mutations in Mtap Cooperate with Myc to Accelerate Tumorigenesis in Mice.

    Directory of Open Access Journals (Sweden)

    Yuwaraj Kadariya

    Full Text Available The gene encoding the methionine salvage pathway methylthioadenosine phosphorylase (MTAP is a tumor suppressor gene that is frequently inactivated in a wide variety of human cancers. In this study, we have examined if heterozygosity for a null mutation in Mtap (Mtap(lacZ could accelerate tumorigenesis development in two different mouse cancer models, Eμ-myc transgenic and Pten(+/- .Mtap Eμ-myc and Mtap Pten mice were generated and tumor-free survival was monitored over time. Tumors were also examined for a variety of histological and protein markers. In addition, microarray analysis was performed on the livers of Mtap(lacZ/+ and Mtap (+/+ mice.Survival in both models was significantly decreased in Mtap(lacZ/+ compared to Mtap(+/+ mice. In Eµ-myc mice, Mtap mutations accelerated the formation of lymphomas from cells in the early pre-B stage, and these tumors tended to be of higher grade and have higher expression levels of ornithine decarboxylase compared to those observed in control Eµ-myc Mtap(+/+ mice. Surprisingly, examination of Mtap status in lymphomas in Eµ-myc Mtap(lacZ/+ and Eµ-myc Mtap(+/+ animals did not reveal significant differences in the frequency of loss of Mtap protein expression, despite having shorter latency times, suggesting that haploinsufficiency of Mtap may be playing a direct role in accelerating tumorigenesis. Consistent with this idea, microarray analysis on liver tissue from age and sex matched Mtap(+/+ and Mtap(lacZ/+ animals found 363 transcripts whose expression changed at least 1.5-fold (P<0.01. Functional categorization of these genes reveals enrichments in several pathways involved in growth control and cancer.Our findings show that germline inactivation of a single Mtap allele alters gene expression and enhances lymphomagenesis in Eµ-myc mice.

  13. LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells.

    Science.gov (United States)

    Wei, Q; Chen, Z-H; Wang, L; Zhang, T; Duan, L; Behrens, C; Wistuba, I I; Minna, J D; Gao, B; Luo, J-H; Liu, Z P

    2016-05-19

    Lung cancer is the leading cause of cancer-related death in the United States, and metastatic behavior is largely responsible for this mortality. Mutations in multiple 'driver' oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor-like 1 (LZTFL1) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previously, we found that LZTFL1 is downregulated in epithelial tumors, including lung cancer, and functions as a tumor suppressor in gastric cancers. However, the functional role of LZTFL1 in lung oncogenesis is undefined. We show here that downregulation of LZTFL1 expression in non-small cell lung cancer is associated with recurrence and poor survival, whereas re-expression of LZTFL1 in lung tumor cells inhibited extravasation/colonization of circulating tumor cells to the lung and inhibited tumor growth in vivo. Mechanistically, we found that LZTFL1 is expressed in ciliated human bronchial epithelial cells (HBECs) and its expression correlates with HBEC differentiation. LZTFL1 inhibits transforming growth factor β-activated mitogen-activated protein kinase and hedgehog signaling. Alteration of intracellular levels of LZTFL1 resulted in changes of expression of genes associated with epithelial-to-mesenchymal transition (EMT). We conclude that LZTFL1 inhibits lung tumorigenesis, possibly by maintaining epithelial cell differentiation and/or inhibition of signalings that lead to EMT and suggest that reactivation of LZTFL1 expression in tumor cells may be a novel lung cancer therapeutic approach. PMID:26364604

  14. A Novel Aspect of Tumorigenesis-BMI1 Functions in Regulating DNA Damage Response.

    Science.gov (United States)

    Lin, Xiaozeng; Ojo, Diane; Wei, Fengxiang; Wong, Nicholas; Gu, Yan; Tang, Damu

    2015-01-01

    BMI1 plays critical roles in maintaining the self-renewal of hematopoietic, neural, intestinal stem cells, and cancer stem cells (CSCs) for a variety of cancer types. BMI1 promotes cell proliferative life span and epithelial to mesenchymal transition (EMT). Upregulation of BMI1 occurs in multiple cancer types and is associated with poor prognosis. Mechanistically, BMI1 is a subunit of the Polycomb repressive complex 1 (PRC1), and binds the catalytic RING2/RING1b subunit to form a functional E3 ubiquitin ligase. Through mono-ubiquitination of histone H2A at lysine 119 (H2A-K119Ub), BMI1 represses multiple gene loci; among these, the INK4A/ARF locus has been most thoroughly investigated. The locus encodes the p16INK4A and p14/p19ARF tumor suppressors that function in the pRb and p53 pathways, respectively. Its repression contributes to BMI1-derived tumorigenesis. BMI1 also possesses other oncogenic functions, specifically its regulative role in DNA damage response (DDR). In this process, BMI1 ubiquitinates histone H2A and γH2AX, thereby facilitating the repair of double-stranded DNA breaks (DSBs) through stimulating homologous recombination and non-homologous end joining. Additionally, BMI1 compromises DSB-induced checkpoint activation independent of its-associated E3 ubiquitin ligase activity. We review the emerging role of BMI1 in DDR regulation and discuss its impact on BMI1-derived tumorigenesis. PMID:26633535

  15. High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity

    Science.gov (United States)

    Park, Mi-Young; Kim, Min Young; Seo, Young Rok; Kim, Jong-Sang; Sung, Mi-Kyung

    2016-01-01

    Background: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in ApcMin/+ mice. Methods: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. Results: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2′-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). Conclusions: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis. PMID:27390738

  16. Distribution of LGR5+ cells and associated implications during the early stage of gastric tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Bo Gun Jang

    Full Text Available Lgr5 was identified as a promising gastrointestinal tract stem cell marker in mice. Lineage tracing indicates that Lgr5(+ cells may not only be the cells responsible for the origin of tumors; they may also be the so-called cancer stem cells. In the present study, we investigated the presence of Lgr5(+ cells and their biological significance in normal human gastric mucosa and gastric tumors. RNAscope, a newly developed RNA in situ hybridization technique, specifically labeled Lgr5(+ cells at the basal glands of the gastric antrum. Notably, the number of Lgr5(+ cells was remarkably increased in intestinal metaplasia. In total, 76% of gastric adenomas and 43% of early gastric carcinomas were positive for LGR5. Lgr5(+ cells were found more frequently in low-grade tumors with active Wnt signaling and an intestinal gland type, suggesting that LGR5 is likely involved in the very early stages of Wnt-driven tumorigenesis in the stomach. Interestingly, similar to stem cells in normal tissues, Lgr5(+ cells were often restricted to the base of the tumor glands, and such Lgr5(+ restriction was associated with high levels of intestinal stem cell markers such as EPHB2, OLFM4, and ASCL2. Thus, our findings show that Lgr5(+ cells are present at the base of the antral glands in the human stomach and that this cell population significantly expands in intestinal metaplasias. Furthermore, Lgr5(+ cells are seen in a large number of gastric tumors ; their frequent basal arrangements and coexpression of ISC markers support the idea that Lgr5(+ cells act as stem cells during the early stage of intestinal-type gastric tumorigenesis.

  17. Constitutive activation of STAT3 in breast cancer cells: A review.

    Science.gov (United States)

    Banerjee, Kasturi; Resat, Haluk

    2016-06-01

    Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in numerous cancer types, including more than 40% of breast cancers. In contrast to tight regulation of STAT3 as a latent transcription factor in normal cells, its signaling in breast cancer oncogenesis is multifaceted. Signaling through the IL-6/JAK/STAT3 pathway initiated by the binding of IL-6 family of cytokines (i.e., IL-6 and IL-11) to their receptors have been implicated in breast cancer development. Receptors with intrinsic kinase activity such as EGFR and VEGFR directly or indirectly induce STAT3 activation in various breast cancer types. Aberrant STAT3 signaling promotes breast tumor progression through deregulation of the expression of downstream target genes which control proliferation (Bcl-2, Bcl-xL, Survivin, Cyclin D1, c-Myc and Mcl-1), angiogenesis (Hif1α and VEGF) and epithelial-mesenchymal transition (Vimentin, TWIST, MMP-9 and MMP-7). These multiple modes of STAT3 regulation therefore make it a central linking point for a multitude of signaling processes. Extensive efforts to target STAT3 activation in breast cancer had no remarkable success in the past because the highly interconnected nature of STAT3 signaling introduces lack of selectivity in pathway identification for STAT3 targeted molecular therapies or because its role in tumorigenesis may not be as critical as it was thought. This review provides a full spectrum of STAT3's involvement in breast cancer by consolidating the knowledge about its role in breast cancer development at multiple levels: its differential regulation by different receptor signaling pathways, its downstream target genes, and modification of its transcriptional activity by its coregulatory transcription factors. PMID:26559373

  18. Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

    Science.gov (United States)

    Fu, De-Yuan; Tan, Hao-Sheng; Wei, Jin-Li; Zhu, Chang-Ren; Jiang, Ji-Xin; Zhu, Yu-Xiang; Cai, Feng-Lin; Chong, Mei-Hong; Ren, Chuan-Li

    2015-09-01

    The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate analyses indicated that lower SOX17 expression was an independent prognostic factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer. PMID:25971583

  19. Methylation profiling of 48 candidate genes in tumor and matched normal tissues from breast cancer patients.

    Science.gov (United States)

    Li, Zibo; Guo, Xinwu; Wu, Yepeng; Li, Shengyun; Yan, Jinhua; Peng, Limin; Xiao, Zhi; Wang, Shouman; Deng, Zhongping; Dai, Lizhong; Yi, Wenjun; Xia, Kun; Tang, Lili; Wang, Jun

    2015-02-01

    Gene-specific methylation alterations in breast cancer have been suggested to occur early in tumorigenesis and have the potential to be used for early detection and prevention. The continuous increase in worldwide breast cancer incidences emphasizes the urgent need for identification of methylation biomarkers for early cancer detection and patient stratification. Using microfluidic PCR-based target enrichment and next-generation bisulfite sequencing technology, we analyzed methylation status of 48 candidate genes in paired tumor and normal tissues from 180 Chinese breast cancer patients. Analysis of the sequencing results showed 37 genes differentially methylated between tumor and matched normal tissues. Breast cancer samples with different clinicopathologic characteristics demonstrated distinct profiles of gene methylation. The methylation levels were significantly different between breast cancer subtypes, with basal-like and luminal B tumors having the lowest and the highest methylation levels, respectively. Six genes (ACADL, ADAMTSL1, CAV1, NPY, PTGS2, and RUNX3) showed significant differential methylation among the 4 breast cancer subtypes and also between the ER +/ER- tumors. Using unsupervised hierarchical clustering analysis, we identified a panel of 13 hypermethylated genes as candidate biomarkers that performed a high level of efficiency for cancer prediction. These 13 genes included CST6, DBC1, EGFR, GREM1, GSTP1, IGFBP3, PDGFRB, PPM1E, SFRP1, SFRP2, SOX17, TNFRSF10D, and WRN. Our results provide evidence that well-defined DNA methylation profiles enable breast cancer prediction and patient stratification. The novel gene panel might be a valuable biomarker for early detection of breast cancer. PMID:25636590

  20. Breast abscesses after breast conserving therapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Kazuhisa [National Kyoto Hospital (Japan)

    2001-09-01

    Breast abscess after breast conserving therapy is a rare complication and the study of this cause has not been reported. A retrospective review of 190 patients undergoing breast conserving therapy in our institution revealed 4 patients with breast abscess (mean age, 50.6 years; range, 47-57 years and median follow up 4 months; 1-11 months). Risk factors which were common to all patients were: fine needle aspiration (FNA), surgical treatment; wide excision, adjuvant therapy; oral administration of tamoxifen (TAM), radiation therapy (RT) to ipsilateral whole breast; total dose of 50 Gy and skin desquamation by RT; level I or II. Other important risk factors in 3 patients were repeated aspirations of seroma post operatively and 2 patients received chemotherapy; CAF. Cultures from one abscess grew staphylococcus aureus, one grew staphylococcus epidermidis, and two were sterile. Breast abscess may be caused by a variety of factors and it is often difficult to specify the cause. This suggests that careful observation will be necessary to determine the cause. (author)

  1. Breast abscesses after breast conserving therapy for breast cancer

    International Nuclear Information System (INIS)

    Breast abscess after breast conserving therapy is a rare complication and the study of this cause has not been reported. A retrospective review of 190 patients undergoing breast conserving therapy in our institution revealed 4 patients with breast abscess (mean age, 50.6 years; range, 47-57 years and median follow up 4 months; 1-11 months). Risk factors which were common to all patients were: fine needle aspiration (FNA), surgical treatment; wide excision, adjuvant therapy; oral administration of tamoxifen (TAM), radiation therapy (RT) to ipsilateral whole breast; total dose of 50 Gy and skin desquamation by RT; level I or II. Other important risk factors in 3 patients were repeated aspirations of seroma post operatively and 2 patients received chemotherapy; CAF. Cultures from one abscess grew staphylococcus aureus, one grew staphylococcus epidermidis, and two were sterile. Breast abscess may be caused by a variety of factors and it is often difficult to specify the cause. This suggests that careful observation will be necessary to determine the cause. (author)

  2. Expression of Toll-Like Receptors on Breast Tumors: Taking a Toll on Tumor Microenvironment

    International Nuclear Information System (INIS)

    Breast cancer remains a major cause of death in women in the developed world. As Toll-like receptors (TLRs) are widely expressed on tumor cells and play important roles in the initiation and progression of cancer, they may thus serve as important targets and have an effective perspective on breast cancer treatment. Expression of TLRs on breast cancer cells and mononuclear inflammatory cells can promote inflammation and cell survival in the tumor microenvironment. Inflammation and cancer are related. It is well known that persistent inflammatory conditions can induce cancer formation, due to production of cytokines and chemokines, which play a crucial role in promoting angiogenesis, metastasis, and subversion of adaptive immunity. TLR signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. This paper delineates the expression of various TLRs in promotion of inflammation and development of mammary tumors. Understanding the mechanisms through which TLRs on breast cancer cells and inflammatory cells regulate growth, survival, and metastatic progression can make them potential targets for breast cancer therapy

  3. Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

    International Nuclear Information System (INIS)

    Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients

  4. Critical role of c-Jun overexpression in liver metastasis of human breast cancer xenograft model

    International Nuclear Information System (INIS)

    c-Jun/AP-1 has been linked to invasive properties of aggressive breast cancer. Recently, it has been reported that overexpression of c-Jun in breast cancer cell line MCF-7 resulted in increased AP-1 activity, motility and invasiveness of the cells in vitro and tumor formation in nude mice. However, the role of c-Jun in metastasis of human breast cancer in vivo is currently unknown. To further investigate the direct involvement of c-Jun in tumorigenesis and metastasis, in the present study, the effects of c-Jun overexpression were studied in both in vitro and in nude mice. Ectopic overexpression of c-Jun promoted the growth of MCF-7 cells and resulted in a significant increase in the percentage of cells in S phase and increased motility and invasiveness. Introduction of c-Jun gene alone into weakly invasive MCF-7 cells resulted in the transfected cells capable of metastasizing to the nude mouse liver following tail vein injection. The present study confirms that overexpression of c-Jun contributes to a more invasive phenotype in MCF-7 cells. It indicates an interesting relationship between c-Jun expression and increased property of adhesion, migration and in vivo liver metastasis of MCF-7/c-Jun cells. The results provide further evidence that c-Jun is involved in the metastasis of breast cancer. The finding also opens an opportunity for development of anti-c-Jun strategies in breast cancer therapy

  5. Dysregulated miR-183 inhibits migration in breast cancer cells.

    LENUS (Irish Health Repository)

    Lowery, Aoife J

    2010-01-01

    The involvement of miRNAs in the regulation of fundamental cellular functions has placed them at the fore of ongoing investigations into the processes underlying carcinogenesis. MiRNA expression patterns have been shown to be dysregulated in numerous human malignancies, including breast cancer, suggesting their probable involvement as novel classes of oncogenes or tumour suppressor genes. The identification of differentially expressed miRNAs and elucidation of their functional roles may provide insight into the complex and diverse molecular mechanisms of tumorigenesis. MiR-183 is located on chromosome 7q32 and is part of a miRNA family which are dysregulated in numerous cancers. The aims of this study were to further examine the expression and functional role of miR-183 in breast cancer.

  6. Analysis of secretome of breast cancer cell line with an optimized semi-shotgun method

    International Nuclear Information System (INIS)

    Secretome, the totality of secreted proteins, is viewed as a promising pool of candidate cancer biomarkers. Simple and reliable methods for identifying secreted proteins are highly desired. We used an optimized semi-shotgun liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) method to analyze the secretome of breast cancer cell line MDA-MB-231. A total of 464 proteins were identified. About 63% of the proteins were classified as secreted proteins, including many promising breast cancer biomarkers, which were thought to be correlated with tumorigenesis, tumor development and metastasis. These results suggest that the optimized method may be a powerful strategy for cell line secretome profiling, and can be used to find potential cancer biomarkers with great clinical significance. (authors)

  7. The dual role of FOXF2 in regulation of DNA replication and the epithelial-mesenchymal transition in breast cancer progression.

    Science.gov (United States)

    Lo, Pang-Kuo; Lee, Ji Shin; Liang, Xiaohui; Sukumar, Saraswati

    2016-10-01

    Dysregulation of Forkhead-box (FOX) transcription factors is linked to cancers of numerous tissue types. Here, we report that FOXF2 is frequently silenced in luminal-type and HER2-positive breast cancers, but is overexpressed in basal-like breast cancers; thus, FOXF2 appears to play distinct roles in different breast cancer subtypes. Inactivation of FOXF2 in luminal-type and HER2-positive breast cancers is attributable to epigenetic silencing. Silencing of FOXF2 is associated with poor prognosis in luminal-type breast cancer. Ectopic expression of FOXF2 in luminal and HER2-positive breast cancer cells suppresses their tumorigenic properties in vitro and in vivo via inhibition of the CDK2-RB-E2F cascade. The in vivo function of FOXF2 is to maintain the stringency of DNA replication, and its loss triggers dysregulation of DNA replication, which in turn activates the p53 checkpoint pathway. Besides its role in cell cycle regulation, FOXF2 is functionally required for mobility and epithelial-to-mesenchymal transition (EMT) of normal breast epithelial cells. In basal-like breast cancer cells, the cell-cycle function of FOXF2 is impaired. However, the EMT function of FOXF2 is still required for mobility, invasiveness and anchorage-independent growth of basal-like breast cancer cells. Our gene expression profiling studies demonstrate that FOXF2 regulates the expression of genes implicated in cell cycle and EMT regulation. Moreover, FOXF2 is highly co-expressed with basal- and metastasis-related genes in breast cancer. These findings suggest that FOXF2 has a dual role in breast tumorigenesis and functions as either a tumor suppressor or an oncogene depending on the breast tumor subtype. PMID:27377963

  8. 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 ...

  9. Contralateral breast cancer risk

    International Nuclear Information System (INIS)

    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

  10. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

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

  11. Breast Cancer Rates by State

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English Español (Spanish) Recommend ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  12. CDC Vital Signs: Breast Cancer

    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 ...

  13. Your Body After Breast Cancer

    Science.gov (United States)

    ... Breast Cancer , Coping with Cancer Your Body After Breast Cancer Article date: September 28, 2012 By Melissa Weber ... age 24, she was diagnosed with stage 3 breast cancer in 2010. “I had no control over what ...

  14. 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 ...

  15. Breast reconstruction in conserving breast cancer surgery

    International Nuclear Information System (INIS)

    Breast conserving treatment (BCT) combined with radiotherapy have provedthe test of time as a sound oncological operation regarding survival andlocal recurrence. Successful BCT is a balance between adequate surgery andmaintaining the breast's appearance. Unsatisfactory outcome reaches 20-30% instandard techniques of BCD. Concepts described to widen the spectrum of BCT,have made an improvement of cosmetic outcome and facilitated a liberal safetymargin. Volume displacement techniques, such as glandular flap, mammoplasty,donut mastopexy and batwing mastopexy proved useful in large breasts andvolume replacement, such as latissimus dorsi flap and local flaps are ofgreat advantage to replace defects in small and medium sized breasts. Some ofthese techniques are simple, but comprehensive knowledge and training arerequired for sophisticated ones. The objectives of this article are to shedlight on different techniques adopted by surgeons to perform BCT inconjunction with various oncoplastic techniques and to discuss the factorsthat influence their applications to achieve best oncological and aestheticoutcome. (author)

  16. Breast motion asymmetry during running

    OpenAIRE

    Mills, Chris; Risius, Debbie; Scurr, Joanna

    2015-01-01

    Breast asymmetry is common in females, despite a similar driving force; dynamic activity may result in asymmetrical breast motion. This preliminary study investigated how breast categorisation (left/right or dominant/non-dominant) may affect breast support recommendations and its relationship with breast pain. Ten females ran on a treadmill at 10 kph in three breast supports (no bra, everyday bra, sports bra). Five reflective markers on the thorax and nipples were tracked using infrared camer...

  17. Over-expression of ST3Gal-I promotes mammary tumorigenesis

    DEFF Research Database (Denmark)

    Picco, Gianfranco; Julien, Sylvain; Brockhausen, Inka; Beatson, Richard; Antonopoulos, Aristotelis; Haslam, Stuart; Mandel, Ulla; Dell, Anne; Pinder, Sarah; Taylor-Papadimitriou, Joyce; Burchell, Joy

    2010-01-01

    3Gal-I adds sialic acid to the galactose residue of core 1 (Galbeta1,3GalNAc) O-glycans and this enzyme is over-expressed in breast cancer resulting in the expression of sialylated core 1 glycans. In order to study the role of ST3Gal-I in mammary tumor development, we developed transgenic mice that...

  18. Separation Anxiety: Detachment from the Extracellular Matrix Induces Metabolic Changes that Can Stimulate Tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Magdalena A. Cichon; Derek C. Radisky

    2010-01-01

    @@ One of the earliest stages of tumor progression involves the ability of cells to survive and proliferate when not attached to the extracellular matrix (ECM). New research using a physiologically relevant breast cancer model reveals how separation from the ECM stimulates metabolic changes characteristic of developing tumors.

  19. Oxalate induces breast cancer

    OpenAIRE

    Castellaro, Andrés M.; Tonda, Alfredo; Cejas, Hugo H.; Ferreyra, Héctor; Caputto, Beatriz L.; Pucci, Oscar A.; Gil, German A.

    2015-01-01

    Background Microcalcifications can be the early and only presenting sign of breast cancer. One shared characteristic of breast cancer is the appearance of mammographic mammary microcalcifications that can routinely be used to detect breast cancer in its initial stages, which is of key importance due to the possibility that early detection allows the application of more conservative therapies for a better patient outcome. The mechanism by which mammary microcalcifications are formed is still l...

  20. Familial breast cancer.

    OpenAIRE

    Phipps, R. F.; Perry, P M

    1988-01-01

    Familial breast cancer is important because of all the known risk factors associated with developing the disease. The one with the most predictability is a positive family history. It is also important because a family history causes anxiety in the families concerned, and young women will often ask their chance of developing the disease. This form of breast cancer accounts for 10% of causes and has factors that distinguish it from the sporadic variety. Relatives of familial breast cancer pati...

  1. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    Science.gov (United States)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison M; Easton, Douglas F; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Fasching, Peter A; Haeberle, Lothar; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marmé, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Nielsen, Sune F; Nordestgaard, Børge G; González-Neira, Anna; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Dörk, Thilo; Bogdanova, Natalia V; Mannermaa, Arto; Hartikainen, Jaana M; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; García-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S; Pharoah, Paul D P; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry. PMID:26621531

  2. Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

    Science.gov (United States)

    2015-06-23

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  3. Neuroendocrine breast cancer

    OpenAIRE

    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-01-01

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast l...

  4. Bacteria, plankton, and trace metal, and other data from bottle and CTD casts in the Antarctic from the NATHANIEL B. PALMER and ROGER REVELL in support of the US Joint Global Ocean Flux Study / Antarctic Environments Southern Ocean Process Study (JGOFS /AESOPS) from 1996-10-17 to 1998-03-15 (NODC Accession 0000504)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Phytoplankton and other data were collected in the Antarctic from the NATHANIEL B. PALMER and ROGER REVELL from 17 October 1996 to 15 March 1998. Bottle data...

  5. C2- and C4-position 17β-estradiol metabolites and their relation to breast cancer

    Directory of Open Access Journals (Sweden)

    Annie Joubert

    2009-12-01

    Full Text Available C2- and C4-position 17β-estradiol metabolites play an important role in breast carcinogenesis. 2-Hydroxyestradiol and 4-hydroxyestradiol are implicated in tumorigenesis via two pathways. These pathways entail increased cell proliferation and the formation of reactive oxygen species that trigger an increase in the likelihood of deoxyribonucleic acid mutations. 2-Methoxyestradiol, a 17β-estradiol metabolite, however, causes induction of apoptosis in transformed and tumor cells; thus exhibiting an antiproliferative effect on tumor growth. The 4-hydroxyestradiol:2-methoxyestradiol and 2-hydroxyestradiol:2-methoxyestradiol ratios therefore ought to be taken into account as possible indicators of carcinogenesis.

  6. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  7. Heterozygous inactivation of tsc2 enhances tumorigenesis in p53 mutant zebrafish

    Directory of Open Access Journals (Sweden)

    Seok-Hyung Kim

    2013-07-01

    Tuberous sclerosis complex (TSC is a multi-organ disorder caused by mutations of the TSC1 or TSC2 genes. A key function of these genes is to inhibit mTORC1 (mechanistic target of rapamycin complex 1 kinase signaling. Cells deficient for TSC1 or TSC2 have increased mTORC1 signaling and give rise to benign tumors, although, as a rule, true malignancies are rarely seen. In contrast, other disorders with increased mTOR signaling typically have overt malignancies. A better understanding of genetic mechanisms that govern the transformation of benign cells to malignant ones is crucial to understand cancer pathogenesis. We generated a zebrafish model of TSC and cancer progression by placing a heterozygous mutation of the tsc2 gene in a p53 mutant background. Unlike tsc2 heterozygous mutant zebrafish, which never exhibited cancers, compound tsc2;p53 mutants had malignant tumors in multiple organs. Tumorigenesis was enhanced compared with p53 mutant zebrafish. p53 mutants also had increased mTORC1 signaling that was further enhanced in tsc2;p53 compound mutants. We found increased expression of Hif1-α, Hif2-α and Vegf-c in tsc2;p53 compound mutant zebrafish compared with p53 mutant zebrafish. Expression of these proteins probably underlies the increased angiogenesis seen in compound mutant zebrafish compared with p53 mutants and might further drive cancer progression. Treatment of p53 and compound mutant zebrafish with the mTORC1 inhibitor rapamycin caused rapid shrinkage of tumor size and decreased caliber of tumor-associated blood vessels. This is the first report using an animal model to show interactions between tsc2, mTORC1 and p53 during tumorigenesis. These results might explain why individuals with TSC rarely have malignant tumors, but also suggest that cancer arising in individuals without TSC might be influenced by the status of TSC1 and/or TSC2 mutations and be potentially treatable with mTORC1 inhibitors.

  8. SHP2E76K mutant promotes lung tumorigenesis in transgenic mice.

    Science.gov (United States)

    Schneeberger, Valentina E; Luetteke, Noreen; Ren, Yuan; Berns, Hartmut; Chen, Liwei; Foroutan, Parastou; Martinez, Gary V; Haura, Eric B; Chen, Jiandong; Coppola, Domenico; Wu, Jie

    2014-08-01

    Lung cancer is a major disease carrying heterogeneous molecular lesions and many of them remain to be analyzed functionally in vivo. Gain-of-function (GOF) SHP2 (PTPN11) mutations have been found in various types of human cancer, including lung cancer. However, the role of activating SHP2 mutants in lung cancer has not been established. We generated transgenic mice containing a doxycycline (Dox)-inducible activating SHP2 mutant (tetO-SHP2(E76K)) and analyzed the role of SHP2(E76K) in lung tumorigenesis in the Clara cell secretory protein (CCSP)-reverse tetracycline transactivator (rtTA)/tetO-SHP2(E76K) bitransgenic mice. SHP2(E76K) activated Erk1/Erk2 (Erk1/2) and Src, and upregulated c-Myc and Mdm2 in the lungs of bitransgenic mice. Atypical adenomatous hyperplasia and small adenomas were observed in CCSP-rtTA/tetO-SHP2(E76K) bitransgenic mice induced with Dox for 2-6 months and progressed to larger adenoma and adenocarcinoma by 9 months. Dox withdrawal from bitransgenic mice bearing magnetic resonance imaging-detectable lung tumors resulted in tumor regression. These results show that the activating SHP2 mutant promotes lung tumorigenesis and that the SHP2 mutant is required for tumor maintenance in this mouse model of non-small cell lung cancer. SHP2(E76K) was associated with Gab1 in the lung of transgenic mice. Elevated pGab1 was observed in the lung of Dox-induced CCSP-rtTA/tetO-SHP2(E76K) mice and in cell lines expressing SHP2(E76K), indicating that the activating SHP2 mutant autoregulates tyrosine phosphorylation of its own docking protein. Gab1 tyrosine phosphorylation is sensitive to inhibition by the Src inhibitor dasatinib in GOF SHP2-mutant-expressing cells, suggesting that Src family kinases are involved in SHP2 mutant-induced Gab1 tyrosine phosphorylation. PMID:24480804

  9. Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Li Xiangping

    2009-09-01

    Full Text Available Abstract Background Human Cripto-1, a member of the EGF-CFC family, is indispensable for early embryonic development. Cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet little is known about Cripto-1 in nasopharyngeal carcinoma (NPC. The aim of this study was to analyze the roles of Cripto-1 in the progression and clinical characteristics in NPC clinical samples and cell lines. Methods The expression of Cripto-1 at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR and real time RT-PCR, and western blot was used to examine the protein expression. Cripto-1 expression and its clinical characteristics were investigated by performing immunohistochemical analysis on a total of 37 NPC clinical tissue samples. Lentiviral vectors were constructed to get an efficient expression of anti-Cripto-1 siRNA in CNE-2 and C666-1 cells, with invalid RNAi sequence as control. After the inhibition of the endogenous Cripto-1, the growth, cell cycle and invasion of cells were detected by MTT, FACS and Boyden chamber assay respectively. Moreover, in vivo, the proliferation of the tumor cells was evaluated in xenotransplant nude mice model with whole-body visualizing instrument. Results The results of real-time RT-PCR and western blot showed that the expression level of Cripto-1 was markedly higher in NPC cell lines than that in the immortalized nasopharyngeal epithelial cell at both mRNA and protein levels. RT-PCR of 17 NPC tissues showed a high expression rate in 76.5% (13/17 cases. In an immunohistochemical study, Cripto-1 was found to express in 54.1% (20/37 cases of NPC. In addition, Cripto-1 overexpression was significantly associated with N classification (p = 0.034, distant metastasis (p = 0.036, and clinical stage (p = 0.007. Inhibition of endogenous Cripto-1 by lentivirus-mediated RNAi silencing technique suppressed NPC cell growth and invasion

  10. Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Human Cripto-1, a member of the EGF-CFC family, is indispensable for early embryonic development. Cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet little is known about Cripto-1 in nasopharyngeal carcinoma (NPC). The aim of this study was to analyze the roles of Cripto-1 in the progression and clinical characteristics in NPC clinical samples and cell lines. The expression of Cripto-1 at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Cripto-1 expression and its clinical characteristics were investigated by performing immunohistochemical analysis on a total of 37 NPC clinical tissue samples. Lentiviral vectors were constructed to get an efficient expression of anti-Cripto-1 siRNA in CNE-2 and C666-1 cells, with invalid RNAi sequence as control. After the inhibition of the endogenous Cripto-1, the growth, cell cycle and invasion of cells were detected by MTT, FACS and Boyden chamber assay respectively. Moreover, in vivo, the proliferation of the tumor cells was evaluated in xenotransplant nude mice model with whole-body visualizing instrument. The results of real-time RT-PCR and western blot showed that the expression level of Cripto-1 was markedly higher in NPC cell lines than that in the immortalized nasopharyngeal epithelial cell at both mRNA and protein levels. RT-PCR of 17 NPC tissues showed a high expression rate in 76.5% (13/17) cases. In an immunohistochemical study, Cripto-1 was found to express in 54.1% (20/37) cases of NPC. In addition, Cripto-1 overexpression was significantly associated with N classification (p = 0.034), distant metastasis (p = 0.036), and clinical stage (p = 0.007). Inhibition of endogenous Cripto-1 by lentivirus-mediated RNAi silencing technique suppressed NPC cell growth and invasion in vitro. In vivo, the average weight (p = 0

  11. Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

    Directory of Open Access Journals (Sweden)

    Pham Phuc V

    2011-12-01

    Full Text Available Abstract Background Breast cancer stem cells (BCSCs are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs. Methods We isolated a breast cancer cell population (CD44+CD24- cells from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Results Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Conclusions Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.

  12. The internally truncated LRP5 receptor presents a therapeutic target in breast cancer.

    Directory of Open Access Journals (Sweden)

    Peyman Björklund

    Full Text Available BACKGROUND: Breast cancer is a common malignant disease, which may be caused by a number of genes deregulated by genomic or epigenomic events. Deregulated WNT/beta-catenin signaling with accumulation of beta-catenin is common in breast tumors, but mutations in WNT signaling pathway components have been rare. An aberrantly spliced internally truncated LRP5 receptor (LRP5Delta666-809, LRP5Delta was shown recently to be resistant to DKK1 inhibition, and was required for beta-catenin accumulation in hyperparathyroid tumors and parathyroid tumor growth. METHODOLOGY/PRINCIPAL FINDINGS: Here we show, by reverse transcription PCR and Western blot analysis, that LRP5Delta is frequently expressed in breast tumors of different cancer stage (58-100%, including carcinoma in situ and metastatic carcinoma. LRP5Delta was required in MCF7 breast cancer cells for the non-phosphorylated active beta-catenin level, transcription activity of beta-catenin, cell growth in vitro, and breast tumor growth in a xenograft SCID mouse model. WNT3 ligand, but not WNT1 and WNT3A augmented the endogenous beta-catenin activity of MCF7 cells in a DKK1-insensitive manner. Furthermore, an anti-LRP5 antibody attenuated beta-catenin activity, inhibited cell growth, and induced apoptosis in LRP5Delta-positive MCF7 and T-47D breast cancer cells, but not in control cells. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the LRP5Delta receptor is strongly implicated in mammary gland tumorigenesis and that its aberrant expression present an early event during disease progression. LRP5 antibody therapy may have a significant role in the treatment of breast cancer.

  13. 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.

  14. 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.

  15. Effect of Rosmarinus officinalis in modulating 7,12-dimethylbenz(a)anthracene induced skin tumorigenesis in mice.

    Science.gov (United States)

    Sancheti, Garima; Goyal, P K

    2006-11-01

    The chemopreventive potential of rosemary (Rosmarinus officinalis) on 7,12-dimethlybenz(a)anthracene (DMBA) initiated and croton oil promoted mouse skin tumorigenesis was assessed. The modulatory effects of R. officinalis was monitored on the basis of the average latency period, tumor incidence, tumor burden, tumor yield, tumor weight and diameter as well as lipid peroxidation and glutathione level. The results indicate that R. officinalis leaves extract could prolong the latency period of tumor occurrence, decrease the tumor incidence, tumor burden and tumor yield. The average weight and diameter of tumors recorded were comparatively lower in the rosemary extract treated mouse groups. The level of lipid peroxidation was significantly reduced in blood serum and liver. Furthermore, depleted levels of glutathione were restored in RE-administered animal groups. Thus, at a dose rate of 500 mg/kg body wt/mouse, the oral administration of rosemary extract was found to be significantly protective against two-stage skin tumorigenesis. PMID:16927448

  16. Girls' Attitudes toward Breast Care and Breast Self-Examination.

    Science.gov (United States)

    Hadranyi, B. T.

    A study explored girls' emerging attitudes toward breast care and breast self-exam (BSE) and the extent to which girls had given thought to these issues. Analyses focused specifically on individual differences related to age, stage of breast development, perceived normalcy of breast development, and body image. The sample consisted of 43 white,…

  17. Synchronous bilateral breast cancer in a male

    OpenAIRE

    Rubio Hernández, María Caridad; Díaz Prado, Yenia Ivet; Pérez, Suanly Rodríguez; Díaz, Ronald Rodríguez; Aleaga, Zaili Gutiérrez

    2013-01-01

    Male breast cancer, which represents only 1% of all breast cancers, is occasionally associated with a family history of breast cancer. Sporadic male breast cancers presenting with another primary breast cancer are extremely rare. In this article, we report on a 70-year-old male patient with bilateral multifocal and synchronous breast cancer and without a family history of breast cancer.

  18. Establishment of 3D Co-Culture Models from Different Stages of Human Tongue Tumorigenesis: Utility in Understanding Neoplastic Progression

    Science.gov (United States)

    Sawant, Sharada; Dongre, Harsh; Singh, Archana Kumari; Joshi, Shriya; Costea, Daniela Elena; Mahadik, Snehal; Ahire, Chetan; Makani, Vidhi; Dange, Prerana; Sharma, Shilpi; Chaukar, Devendra; Vaidya, Milind

    2016-01-01

    To study multistep tumorigenesis process, there is a need of in-vitro 3D model simulating in-vivo tissue. Present study aimed to reconstitute in-vitro tissue models comprising various stages of neoplastic progression of tongue tumorigenesis and to evaluate the utility of these models to investigate the role of stromal fibroblasts in maintenance of desmosomal anchoring junctions using transmission electron microscopy. We reconstituted in-vitro models representing normal, dysplastic, and malignant tissues by seeding primary keratinocytes on either fibroblast embedded in collagen matrix or plain collagen matrix in growth factor-free medium. The findings of histomorphometry, immunohistochemistry, and electron microscopy analyses of the three types of 3D cultures showed that the stratified growth, cell proliferation, and differentiation were comparable between co-cultures and their respective native tissues; however, they largely differed in cultures grown without fibroblasts. The immunostaining intensity of proteins, viz., desmoplakin, desmoglein, and plakoglobin, was reduced as the disease stage increased in all co-cultures as observed in respective native tissues. Desmosome-like structures were identified using immunogold labeling in these cultures. Moreover, electron microscopic observations revealed that the desmosome number and their length were significantly reduced and intercellular spaces were increased in cultures grown without fibroblasts when compared with their co-culture counterparts. Our results showed that the major steps of tongue tumorigenesis can be reproduced in-vitro. Stromal fibroblasts play a role in regulation of epithelial thickness, cell proliferation, differentiation, and maintenance of desmosomalanchoring junctions in in-vitro grown tissues. The reconstituted co-culture models could help to answer various biological questions especially related to tongue tumorigenesis. PMID:27501241

  19. Rbpj conditional knockout reveals distinct functions of Notch4/Int3 in mammary gland development and tumorigenesis

    OpenAIRE

    Raafat, A.; Lawson, S; Bargo, S; Klauzinska, M; Strizzi, L; Goldhar, AS; Buono, K; Salomon, D.; Vonderhaar, BK; Callahan, R

    2008-01-01

    Transgenic mice expressing the Notch 4 intracellular domain (ICD) (Int3) in the mammary gland have two phenotypes: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. We have conditionally ablated the Rbpj gene in the mammary glands of mice expressing whey acidic protein (Wap)-Int3. Interestingly, Rbpj knockout mice (Wap-Cre+/Rbpj−/−/ Wap-Int3) have nor...

  20. Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis

    OpenAIRE

    Moore, P S; Orlandini, S.; Zamboni, G; Capelli, P.; Rigaud, G; Falconi, M; Bassi, C.; Lemoine, N. R.; Scarpa, A.

    2001-01-01

    Alterations of K-ras, p53, p16 and DPC4/Smad4 characterize pancreatic ductal cancer (PDC). Reports of inactivation of these latter two genes in pancreatic endocrine tumours (PET) suggest that common molecular pathways are involved in the tumorigenesis of pancreatic exocrine and endocrine epithelia. We characterized 112 primary pancreatic tumours for alterations in p16 and DPC4 and immunohistochemical expression of DPC4. The cases included 34 PDC, 10 intraductal papillary-mucinous tumours (IPM...

  1. Human Cancer Xenografts in Outbred Nude Mice Can Be Confounded by Polymorphisms in a Modifier of Tumorigenesis

    OpenAIRE

    Zeineldin, Maged; Jensen, Derek; Paranjape, Smita R.; Parelkar, Nikhil K.; Jokar, Iman; Vielhauer, George A.; Neufeld, Kristi L.

    2014-01-01

    Tumorigenicity studies often employ outbred nude mice, in the absence of direct evidence that this mixed genetic background will negatively affect experimental outcome. Here we show that outbred nude mice carry two different alleles of Pla2g2a, a genetic modifier of intestinal tumorigenesis in mice. Here, we identify previous unreported linked polymorphisms in the promoter, noncoding and coding sequences of Pla2g2a and show that outbred nude mice from different commercial providers are hetero...

  2. A zebrafish transgenic model of Ewing’s sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis

    Directory of Open Access Journals (Sweden)

    Stefanie W. Leacock

    2012-01-01

    Ewing’s sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing’s sarcoma family tumors (ESFTs, which include peripheral primitive neuroectodermal tumors (PNETs, are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing’s sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing’s sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing’s sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

  3. Bmi1 promotes prostate tumorigenesis via inhibiting p16INK4A and p14ARF expression

    OpenAIRE

    Fan, Catherine; He, Lizhi; Kapoor, Anil; Gillis, Aubrey; Rybak, Adrian P.; Cutz, Jean-Claude; Tang, Damu

    2008-01-01

    Bmi1 promotes prostate tumorigenesis via inhibiting p16INK4A and p14ARF expression correspondence: Corresponding authors. Anil Kapoor is to be contacted at Tel.: +1 (905) 522 1155, ext. 33218; fax: +1 (905) 521 6195. Damu Tang, T3310, St. Joseph?s Hospital, 50 Charlton Ave East, Hamilton, ON, Canada L8N 4A6. Tel.: +1 (905) 522 1155, ext. 35168; fax: +1 (905) 521 6181. (Kapoor, Anil) correspondence: Corresponding authors. Anil Ka...

  4. P-Selectin-Mediated Adhesion between Platelets and Tumor Cells Promotes Intestinal Tumorigenesis in ApcMin/+ Mice

    OpenAIRE

    Qi, Cuiling; Li, Bin; Guo, Simei; WEI, BO; Shao, Chunkui; LI, JIALIN; Yang, Yang; Zhang, Qianqian; Li, Jiangchao; He, Xiaodong; Wang, Lijing; Zhang, Yajie

    2015-01-01

    Studies have indicated that platelets play an important role in tumorigenesis, and an abundance of platelets accumulate in the ovarian tumor microenvironment outside the vasculature. However, whether cancer cells recruit platelets within intestinal tumors and how they signal adherent platelets to enter intestinal tumor tissues remain unknown. Here, we unexpectedly found that large numbers of platelets were deposited within human colorectal tumor specimens using immunohistochemical staining, a...

  5. Epigenetic mediated silencing of EYA4 contributes to tumorigenesis in oral dysplastic cells.

    Science.gov (United States)

    Towle, Rebecca; Truong, Danielle; Garnis, Cathie

    2016-07-01

    Five-year survival rates for oral squamous cell carcinoma (OSCC) have remained at a dismal 50% for the past several decades. Molecular analyses of premalignant tissues are a key means of identifying early foundational drivers of disease, which may be exploitable as biomarkers or therapeutic targets for improving disease outcomes. We previously identified EYA4 as frequently hypermethylated and silenced in premalignant disease based on an analysis of lesion-adjacent normal, dysplasia, and carcinoma in situ/squamous cell carcinoma tissues from the oral cavity. Herein, we further evaluate the role of this putative tumor suppressor gene in transformation of oral tissues and OSCC. By an initial assessment, EYA4 promoter hypermethylation was found in 24/32 (75%) of paired tumor samples in The Cancer Genome Atlas oral cancer data set, with significant correlation noted between methylation status and relative gene expression. To assess the impact of EYA4 in oral tumorigenesis, we overexpressed EYA4 in two oral dysplasia cell lines. Expression of EYA4 caused an increase in cell proliferation, DNA damage repair capabilities, and increased the level of apoptosis. Taken together, we find evidence that EYA4 is a novel tumor suppressor in oral cancer, which becomes methylated and silenced at the premalignant stage and appears to be epigenetically regulated. Further studies are warranted to investigate its role as a marker for progression in oral cancer. © 2016 Wiley Periodicals, Inc. PMID:27015871

  6. Oligonucleotide microarray identifies genes differentially expressed during tumorigenesis of DMBA-induced pancreatic cancer in rats.

    Directory of Open Access Journals (Sweden)

    Jun-Chao Guo

    Full Text Available The extremely dismal prognosis of pancreatic cancer (PC is attributed, at least in part, to lack of early diagnosis. Therefore, identifying differentially expressed genes in multiple steps of tumorigenesis of PC is of great interest. In the present study, a 7,12-dimethylbenzanthraene (DMBA-induced PC model was established in male Sprague-Dawley rats. The gene expression profile was screened using an oligonucleotide microarray, followed by real-time quantitative polymerase chain reaction (qRT-PCR and immunohistochemical staining validation. A total of 661 differentially expressed genes were identified in stages of pancreatic carcinogenesis. According to GO classification, these genes were involved in multiple molecular pathways. Using two-way hierarchical clustering analysis, normal pancreas, acute and chronic pancreatitis, PanIN, early and advanced pancreatic cancer were completely discriminated. Furthermore, 11 upregulated and 142 downregulated genes (probes were found by Mann-Kendall trend Monotone test, indicating homologous genes of rat and human. The qRT-PCR and immunohistochemistry analysis of CXCR7 and UBe2c, two of the identified genes, confirmed the microarray results. In human PC cell lines, knockdown of CXCR7 resulted in decreased migration and invasion. Collectively, our data identified several promising markers and therapeutic targets of PC based on a comprehensive screening and systemic validation.

  7. The molecular mechanism of HOTAIR in tumorigenesis, metastasis, and drug resistance.

    Science.gov (United States)

    Zhou, Xiaolong; Chen, Jin; Tang, Wenru

    2014-12-01

    Long non-coding RNAs have been reported to play an important role in cellular metabolism and development. Homeobox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA, is pervasively over-expressed in most human cancers compared with non-cancerous adjacent tissues. Although many articles have reported that HOTAIR is closely associated with metastasis, epithelial-mesenchymal transition, advanced pathological stage, drug resistance, and poor prognosis, the role of HOTAIR in gene regulation and tumor development is largely unknown, and the potential molecular mechanisms are not completely clear yet. In this review, we summarized the recent progress in the study of the major functions of HOTAIR. miR-331-3p, miR-130a, miR-7, miR-141, HER2, c-MYC, WIF-1, RBM38, PTEN, and Col-1 are involved in the HOTAIR regulation network. We tried to elucidate the molecular mechanisms of HOTAIR in the aspects of tumorigenesis, metastasis, drug resistance, and regulation. PMID:25385164

  8. Fenofibrate Suppresses Oral Tumorigenesis via Reprogramming Metabolic Processes: Potential Drug Repurposing for Oral Cancer

    Science.gov (United States)

    Jan, Chia-Ing; Tsai, Ming-Hsui; Chiu, Chang-Fang; Huang, Yi-Ping; Liu, Chia Jen; Chang, Nai Wen

    2016-01-01

    One anticancer strategy suggests targeting mitochondrial metabolism to trigger cell death through slowing down energy production from the Warburg effect. Fenofibrate is a clinical lipid-lowering agent and an effective anticancer drug. In the present study, we demonstrate that fenofibrate provided novel mechanisms for delaying oral tumor development via the reprogramming of metabolic processes. Fenofibrate induced cytotoxicity by decreasing oxygen consumption rate (OCR) that was accompanied with increasing extracellular acidification rate (ECAR) and reducing ATP content. Moreover, fenofibrate caused changes in the protein expressions of hexokinase II (HK II), pyruvate kinase, pyruvate dehydrogenase, and voltage-dependent anion channel (VDAC), which are associated with the Warburg effect. In addition, fenofibrate reprogrammed the metabolic pathway by interrupting the binding of HK II to VDAC. In an oral cancer mouse model, fenofibrate exhibited both preventive and therapeutic efficacy on oral tumorigenesis. Fenofibrate administration suppressed the incidence rate of tongue lesions, reduced the tumor sizes, decreased the tumor multiplicity, and decreased the immunoreactivities of VDAC and mTOR. The molecular mechanisms involved in fenofibrate's ability to delay tumor development included the down-regulation of mTOR activity via TSC1/2-dependent signaling through activation of AMPK and inactivation of Akt, or via a TSC1/2-independent pathway through direct suppression of raptor. Our findings provide a molecular rationale whereby fenofibrate exerts anticancer and additional beneficial effects for the treatment of oral cancer patients.

  9. Fenofibrate Suppresses Oral Tumorigenesis via Reprogramming Metabolic Processes: Potential Drug Repurposing for Oral Cancer.

    Science.gov (United States)

    Jan, Chia-Ing; Tsai, Ming-Hsui; Chiu, Chang-Fang; Huang, Yi-Ping; Liu, Chia Jen; Chang, Nai Wen

    2016-01-01

    One anticancer strategy suggests targeting mitochondrial metabolism to trigger cell death through slowing down energy production from the Warburg effect. Fenofibrate is a clinical lipid-lowering agent and an effective anticancer drug. In the present study, we demonstrate that fenofibrate provided novel mechanisms for delaying oral tumor development via the reprogramming of metabolic processes. Fenofibrate induced cytotoxicity by decreasing oxygen consumption rate (OCR) that was accompanied with increasing extracellular acidification rate (ECAR) and reducing ATP content. Moreover, fenofibrate caused changes in the protein expressions of hexokinase II (HK II), pyruvate kinase, pyruvate dehydrogenase, and voltage-dependent anion channel (VDAC), which are associated with the Warburg effect. In addition, fenofibrate reprogrammed the metabolic pathway by interrupting the binding of HK II to VDAC. In an oral cancer mouse model, fenofibrate exhibited both preventive and therapeutic efficacy on oral tumorigenesis. Fenofibrate administration suppressed the incidence rate of tongue lesions, reduced the tumor sizes, decreased the tumor multiplicity, and decreased the immunoreactivities of VDAC and mTOR. The molecular mechanisms involved in fenofibrate's ability to delay tumor development included the down-regulation of mTOR activity via TSC1/2-dependent signaling through activation of AMPK and inactivation of Akt, or via a TSC1/2-independent pathway through direct suppression of raptor. Our findings provide a molecular rationale whereby fenofibrate exerts anticancer and additional beneficial effects for the treatment of oral cancer patients. PMID:27313493

  10. PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

    Energy Technology Data Exchange (ETDEWEB)

    Swindall, Amanda F.; Stanley, Jennifer A. [Department of Radiation Oncology Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, Birmingham, AL 35249 (United States); Yang, Eddy S., E-mail: eyang@uab.edu [Department of Radiation Oncology Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, Birmingham, AL 35249 (United States); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35249 (United States); Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35249 (United States)

    2013-07-26

    Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation.

  11. Tumorigenesis and Greenhouse-Effect System Dynamics: Phenomenally Diverse, but Noumenally Similar?

    Science.gov (United States)

    Prakash, Sai

    We present a physicochemical model of tumorigenesis leading to cancer invasion and metastasis. The continuum-theoretic model, congruent with recent experiments, analyzes the plausibility of oncogenic neoplasia-induced cavitation or tensile yielding (plasticity) of the tumoral basement membrane (BM) to activate stromal invasion. The model abstracts a spheroid of normal and cancer cells that grows radially via water and nutrient influx while constrained by a stiffer BM and cell adhesion molecules. It is based on coupled fluid-solid mechanics and ATP-fueled mechano-damped cell kinetics, and uses empirical data alone as parameters. The model predicts the dynamic force and exergy (ATP) fields, and tumor size among other variables, and generates the sigmoidal dynamics of far-from-equilibrium biota. Simulations show that the tumor-membrane system, on neoplastic perturbation, evolves from one homeostatic steady state to another over time. Integrated with system dynamics theory, the model renders a key, emergent tissue-level feedback control perspective of malignancy: neoplastic tumors coupled with pathologically-softened BMs appear to participate in altered autoregulatory behavior, and likely undergo BM cavitation and stress-localized ruptures to their adhesome, with or without invadopoiesis, thereby, initiating invasion. Serendipitously, the results also reveal a noumenal similarity of the tumor-membrane to the earth-atmosphere open reactive system as concerns self-regulation.

  12. β-catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells.

    Directory of Open Access Journals (Sweden)

    Noriko Okumura

    Full Text Available The canonical Wnt/β-catenin signaling pathway plays a crucial role in the maintenance of the balance between proliferation and differentiation throughout embryogenesis and tissue homeostasis. β-Catenin, encoded by the Ctnnb1 gene, mediates an intracellular signaling cascade activated by Wnt. It also plays an important role in the maintenance of various types of stem cells including adult stem cells and cancer stem cells. However, it is unclear if β-catenin is required for the derivation of mouse embryo-derived stem cells. Here, we established β-catenin-deficient (β-cat(Δ/Δ mouse embryo-derived stem cells and showed that β-catenin is not essential for acquiring self-renewal potential in the derivation of mouse embryonic stem cells (ESCs. However, teratomas formed from embryo-derived β-cat(Δ/Δ ESCs were immature germ cell tumors without multilineage differentiated cell types. Re-expression of functional β-catenin eliminated their neoplastic, transformed phenotype and restored pluripotency, thereby rescuing the mutant ESCs. Our findings demonstrate that β-catenin has pleiotropic effects in ESCs; it is required for the differentiation of ESCs and prevents them from acquiring tumorigenic character. These results highlight β-catenin as the gatekeeper in differentiation and tumorigenesis in ESCs.

  13. Cancer-associated splicing variant of tumor suppressor AIMP2/p38: pathological implication in tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Jin Woo Choi

    2011-03-01

    Full Text Available Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38 was first found as a component for a macromolecular tRNA synthetase complex, it was recently discovered to dissociate from the complex and work as a potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through the protective interaction with p53. However, it was not demonstrated whether AIMP2 was indeed pathologically linked to human cancer. In this work, we found that a splicing variant of AIMP2 lacking exon 2 (AIMP2-DX2 is highly expressed by alternative splicing in human lung cancer cells and patient's tissues. AIMP2-DX2 compromised pro-apoptotic activity of normal AIMP2 through the competitive binding to p53. The cells with higher level of AIMP2-DX2 showed higher propensity to form anchorage-independent colonies and increased resistance to cell death. Mice constitutively expressing this variant showed increased susceptibility to carcinogen-induced lung tumorigenesis. The expression ratio of AIMP2-DX2 to normal AIMP2 was increased according to lung cancer stage and showed a positive correlation with the survival of patients. Thus, this work identified an oncogenic splicing variant of a tumor suppressor, AIMP2/p38, and suggests its potential for anti-cancer target.

  14. Long noncoding RNA SNHG1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis.

    Science.gov (United States)

    Zhang, Min; Wang, Wei; Li, Tianyue; Yu, Xiaodong; Zhu, Yufeng; Ding, Feng; Li, Dongsheng; Yang, Tao

    2016-05-01

    Hepatocellular carcinoma (HCC) is the main cause of cancer mortality worldwide. Its poor prognosis is mainly ascribed to high recurrence rate. Identifying novel prognostic biomarkers and therapeutic targets would be vital for HCC management. Long noncoding RNA (lncRNA) is a class of RNA with various roles in tumorigenesis. The aim of this study was to investigate the clinical significance and functions of lncRNA-small nucleolar RNA host gene 1 (SNHG1) in HCC. In this study, we found SNHG1 was upregulated in HCC tissues in comparison with adjacent liver tissues in both publicly available microarray data and our own cohort. High SNHG1 expression was correlated with large tumor size, poor differentiation, and aggressive BCLC stage. Kaplan-Meier survival analysis demonstrated that high SNHG1 expression predicts poor prognosis of HCC patients. Gain-of-function and loss-of function experiments showed that SNHG1 promotes HCC cells proliferation, cell cycle progression, and inhibits HCC cells apoptosis. Further experiments revealed that SNHG1 promotes HCC cells proliferation through inhibiting p53 and p53-target genes expression. Collectively, our results demonstrated the clinical prognostic significance and roles of SNHG1 in HCC, and suggested that SNHG1 may be considered as a prognostic biomarker and therapeutic target for HCC. PMID:27133041

  15. Diallyl sulfide protects against N-nitrosodiethylamine-induced liver tumorigenesis: Role of aldose reductase

    Institute of Scientific and Technical Information of China (English)

    Safinaz S Ibrahim; Noha N Nassar

    2008-01-01

    AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis. METHODS: Male Wistar rats received either NDEA or NDEA together with DAS as protection. Liver energy metabolism was assessed in terms of lactate, pyruvate, lactate/pyruvate, ATP levels, lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD) activities. In addition, membrane disintegration of the liver cells was evaluated by measuring lipid-peroxidation products, measured as malondialdehyde (MDA); nitric oxide (NO) levels; glucose-6-phosphatase (G6Pase), catalase (CAT) and superoxide dismutase (SOD) activities. Uver DNA level, glutathione-S-transferase (GST) and cytochrome c oxidase activities were used as DNA fragmentation indices. Aldose reductase (AR) activity was measured as an index for cancer cells resistant to chemotherapy and histopathological examination was performed on liver sections from different groups. RESULTS: NDEA significantly disturbed liver functions and most of the aforementioned indices. Treatment with DAS significantly restored liver functions and hepatocellular integrity; improved parameters of energy metabolism and suppressed free-radical generation. CONCLUSION: We provide evidence that DAS exerts a protective role on liver functions and tissue integrity in face of enhanced tumorigenesis caused by NDEA, as well as improving cancer-cell sensitivity to chemotherapy. This is mediated through combating oxidative stress of free radicals, improving the energy metabolic state of the cell, and enhancing the activity of G6Pase, GST and AR enzymes.

  16. T-cell activation promotes tumorigenesis in inflammation-associated cancer

    Directory of Open Access Journals (Sweden)

    Lairmore Michael

    2009-12-01

    Full Text Available Abstract Chronic inflammation has long been associated with a wide range of malignancies, is now widely accepted as a risk factor for development of cancer, and has been implicated as a promoter of a variety of cancers including hematopoietic malignancies. We have described a mouse model uniquely suited to examine the link between inflammation and lymphoma in which the Tax oncogene, expressed in activated T and NK cells, perpetuates chronic inflammation that begins as microscopic intraepithelial lesions and develops into inflammatory nodules, subcutaneous tumors, and large granular lymphocytic leukemia. The use of bioluminescent imaging in these mice has expanded our ability to interrogate aspects of inflammation and tumorigenesis non-invasively. Here we demonstrate that bioluminescence induction in these mice correlated with inflammation resulting from wounding, T cell activation, and exposure to chemical agents. In experiments in which long-term effects of inflammation on disease outcome were monitored, the development of lymphoma was promoted by an inflammatory stimulus. Finally we demonstrated that activation of T-cells in T-cell receptor (TCR transgenic TAX-LUC animals dramatically exacerbated the development of subcutaneous TCR- CD16+ LGL tumors. The role of activated T-cells and acquired immunity in inflammation-associated cancers is broadly applicable to hematopoietic malignancies, and we propose these mice will be of use in dissecting mechanisms by which activated T-cells promote lymphomagenesis in vivo.

  17. Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart.

    Directory of Open Access Journals (Sweden)

    Yuzhen Zhang

    Full Text Available BACKGROUND: Induced pluripotent stem cells (iPSCs are a novel candidate for use in cardiac stem cell therapy. However, their intrinsic tumorigenicity requires further investigation prior to use in a clinical setting. In this study we investigated whether undifferentiated iPSCs are tumorigenic after intramyocardial transplantation into immunocompetent allogeneic recipients. METHODOLOGY/PRINCIPAL FINDINGS: We transplanted 2 × 10(4, 2 × 10(5, or 2 × 10(6 cells from the established rat iPSC line M13 intramyocardially into intact or infarcted hearts of immunocompetent allogeneic rats. Transplant duration was 2, 4, or 6 weeks. Histological examination with hematoxylin-eosin staining confirmed that undifferentiated rat iPSCs could generate heterogeneous tumors in both intracardiac and extracardiac sites. Furthermore, tumor incidence was independent of cell dose, transplant duration, and the presence or absence of myocardial infarction. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that allogeneic iPSC transplantation in the heart will likely result in in situ tumorigenesis, and that cells leaked from the beating heart are a potential source of tumor spread, underscoring the importance of evaluating the safety of future iPSC therapy for cardiac disease.

  18. Tumorigenesis in the U.S. radium luminizers: How unsafe was this occupation?

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, R.G.

    1994-05-01

    Dose-response data are presented from the U.S. female workers who were exposed to radium through the painting of luminous dials and who subsequently had their skeletal burdens measured by whole-body counting and radon breath analyses. Lognormal data analyses were done for radium-induced bone sarcomas and head carcinomas after the populations of the respective doses were first determined to be lognormally distributed. The calculated geometric mean and standard deviation for each dose population were used to construct lognormal distributions that subsequently could be used for intercomparisons. To date, a total of 1,391 female luminizers with average estimated skeletal doses below 10 Gy have not shown bone sarcomas or head carcinomas. A primary purpose of this paper is to support the case that {sup 226.228}Ra is one of the radionuclide sources that exemplify in humans a {open_quote}threshold{close_quotes} dose or a dose below which there should be little concern for tumorigenesis.

  19. PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

    International Nuclear Information System (INIS)

    Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation

  20. Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage

    Science.gov (United States)

    Barrett, Caitlyn W.; Reddy, Vishruth K.; Short, Sarah P.; Motley, Amy K.; Lintel, Mary K.; Bradley, Amber M.; Freeman, Tanner; Vallance, Jefferson; Ning, Wei; Parang, Bobak; Poindexter, Shenika V.; Fingleton, Barbara; Chen, Xi; Washington, Mary K.; Wilson, Keith T.; Shroyer, Noah F.; Hill, Kristina E.; Burk, Raymond F.; Williams, Christopher S.

    2015-01-01

    Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment. Reduced SEPP1 function markedly increased M2-polarized macrophages, indicating a role for SEPP1 in macrophage polarization and immune function. Furthermore, compared with partial loss, complete loss of SEPP1 substantially reduced tumor burden, in part due to increased apoptosis. Using intestinal organoid cultures, we found that, compared with those from WT animals, Sepp1-null cultures display increased stem cell characteristics that are coupled with increased ROS production, DNA damage, proliferation, decreased cell survival, and modulation of WNT signaling in response to H2O2-mediated oxidative stress. Together, these data demonstrate that SEPP1 influences inflammatory tumorigenesis by affecting genomic stability, the inflammatory microenvironment, and epithelial stem cell functions. PMID:26053663

  1. PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

    Directory of Open Access Journals (Sweden)

    Eddy S. Yang

    2013-07-01

    Full Text Available Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs, which are difficult to repair and may lead to the more severe DNA double-strand break (DSB. Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation.

  2. A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chen-Si [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); He, Pei-Juin [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Tsai, Nu-Man [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Li, Chi-Han; Yang, Shang-Chih; Hsu, Wei-Tung [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Wu, Ming-Shiang [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Wu, Chang-Jer [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China); Cheng, Tain-Lu [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liao, Kuang-Wen, E-mail: kitchhen@yahoo.com.tw [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)

    2010-02-05

    Helicobacter pylori has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis.

  3. A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis

    International Nuclear Information System (INIS)

    Helicobacter pylori has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis.

  4. Smad4 suppresses the tumorigenesis and aggressiveness of neuroblastoma through repressing the expression of heparanase

    Science.gov (United States)

    Qu, Hongxia; Zheng, Liduan; Jiao, Wanju; Mei, Hong; Li, Dan; Song, Huajie; Fang, Erhu; Wang, Xiaojing; Li, Shiwang; Huang, Kai; Tong, Qiangsong

    2016-01-01

    Heparanase (HPSE) is the only endo-β-D-glucuronidase that is correlated with the progression of neuroblastoma (NB), the most common extracranial malignancy in childhood. However, the mechanisms underlying HPSE expression in NB still remain largely unknown. Herein, through analyzing cis-regulatory elements and mining public microarray datasets, we identified SMAD family member 4 (Smad4) as a crucial transcription regulator of HPSE in NB. We demonstrated that Smad4 repressed the HPSE expression at the transcriptional levels in NB cells. Mechanistically, Smad4 suppressed the HPSE expression through directly binding to its promoter and repressing the lymphoid enhancer binding factor 1 (LEF1)-facilitated transcription of HPSE via physical interaction. Gain- and loss-of-function studies demonstrated that Smad4 inhibited the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by Smad4. In clinical NB specimens, Smad4 was under-expressed and inversely correlated with HPSE levels, while LEF1 was highly expressed and positively correlated with HPSE expression. Patients with high Smad4 expression, low LEF1 or HPSE levels had greater survival probability. These results demonstrate that Smad4 suppresses the tumorigenesis and aggressiveness of NB through repressing the HPSE expression. PMID:27595937

  5. Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis

    Indian Academy of Sciences (India)

    Niladri Ganguly; Suraj P Parihar

    2009-03-01

    Human papillomavirus (HPV) is small, double-stranded DNA virus that infects mucosal and cutaneous epithelial tissue. HPV is sexually transmitted and the viral DNA replicates extrachromosomally. The virus is non-enveloped and has an icosahedral capsid. There are approximately 118 types of HPV, which are characterized as high-risk or low-risk types. High-risk HPVs cause malignant transformation while the low-risk ones cause benign warts and lesions. The expression of E6 and E7 is normally controlled during the normal viral life cycle when viral DNA replicates extrachromosomally. HPV E6 and E7 oncoproteins are overexpressed when the viral genome integrates into the host DNA. Deregulated overexpression of E6 and E7 oncoproteins can cause several changes in cellular pathways and functions leading to malignant transformation of cells and tumorigenesis. In this review, we focus on several cellular mechanisms and pathways that are altered in the presence of E6 and E7, the target proteins of E6 and E7 inside the host cell and how they contribute to the development of the transformed phenotype..

  6. Influence of dietary menhaden oil on 7,12-dimethylbenzanthracene induced mammary tumorigenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    O' Connor, T.P.; Peterson, F.; Campbell, T.C.

    1986-03-05

    The effect of dietary menhaden oil on 7,12-dimethylbenzanthracene (DMBA) induced mammary tumorigenesis was examined in female Sprague-Dawley rats. Rats were obtained at age 28 days and acclimated until age 50 days when they received a single i.g. dose of 5 mg DMBA dissolved in 1 ml corn oil. Rats were then randomly assigned to one of four treatment groups with 25 rats per group. One group was fed a diet based on fish protein (freeze-dried cod) and corn oil (F/C). The second group received a diet based on fish protein and menhaden oil (F/M). The third group received a casein based diet with corn oil as the lipid source (C/C). The fourth group was fed a casein based diet with menhaden oil as the lipid source (C/M). Both the protein and lipid sources were fed at a level of 20% by weight of the diets. Rats were palpated weekly to check for mammary tumor development and the experiment was terminated 24 weeks after DMBA administration. Rats fed menhaden oil as a lipid source (F/M and C/M groups) developed significantly fewer mammary tumors than animals on the corn oil based diets (F/C and C/C groups, respectively). Thus, menhaden oil, rich in omega-3 fatty acids, significantly inhibited the development of DMBA induced mammary tumors in this experiment.

  7. Generation of a mouse model for studying the role of upregulated RTEL1 activity in tumorigenesis.

    Science.gov (United States)

    Wu, Xiaoli; Sandhu, Sumit; Nabi, Zinnatun; Ding, Hao

    2012-10-01

    Regulator of telomere length 1 (RTEL1) is a DNA helicase protein that has been demonstrated to be required for the maintenance of telomere length and genomic stability. It has also been found to be essential for DNA homologous recombination during DNA repairing. Human RTEL1 genomic locus (20q13.3) is frequently amplified in multiple types of human cancers, including hepatocellular carcinoma and gastrointestinal tract tumors, indicating that upregulated RTEL1 activity could be important for tumorigenesis. In this study, we have developed a conditional transgenic mouse model that overexpress mouse Rtel1 in a Cre-excision manner. By crossing with a ubiquitous Cre mouse line, we further demonstrated that these established Rtel1 conditional transgenic mice allow to efficiently and highly express a functional Rtel1 that is able to rescue the embryonic defects of Rtel1 null mouse allele. Furthermore, we demonstrated that more than 70% transgenic mice that widely overexpress Rtel1 developed liver tumors that recapitulate many malignant features of human hepatocellular carcinoma (HCC). Our work not only generated a valuable mouse model for determining the role of RTEL1 in the development of cancers, but also provided the first genetic evidence to support that amplification of RTEL1, as observed in several types of human cancers, is tumorigenic. PMID:22238064

  8. Protein Kinase C alpha (PKCα) dependent signaling mediates endometrial cancer cell growth and tumorigenesis

    Science.gov (United States)

    Haughian, James M.; Reno, Elaine M.; Thorne, Alicia M.; Bradford, Andrew P.

    2009-01-01

    Endometrial cancer is the most common invasive gynecologic malignancy, yet molecular mechanisms and signaling pathways underlying its etiology and pathophysiology remain poorly characterized. We sought to define a functional role for the protein kinase C (PKC) isoform, PKCα, in an established cell model of endometrial adenocarcinoma. Ishikawa cells depleted of PKCα protein grew slower, formed fewer colonies in anchorage-independent growth assays and exhibited impaired xenograft tumor formation in nude mice. Consistent with impaired growth, PKCα knockdown increased levels of the cyclin dependent kinase (CDK) inhibitors p21Cip1/WAF1 (p21) and p27Kip1 (p27). Despite the absence of functional phosphatase and tensin homologue (PTEN) protein in Ishikawa cells, PKCα knockdown reduced Akt phosphorylation at serine 473 and concomitantly inhibited phosphorylation of the Akt target, glycogen synthase kinase-3β (GSK-3β). PKCα knockdown also resulted in decreased basal ERK phosphorylation and attenuated ERK activation following EGF stimulation. p21 and p27 expression was not increased by treatment of Ishikawa cells with ERK and Akt inhibitors, suggesting PKCα regulates CDK expression independently of Akt and ERK. Immunohistochemical analysis of grade 1 endometrioid adenocarcinoma revealed aberrant PKCα expression, with foci of elevated PKCα staining, not observed in normal endometrium. These studies demonstrate a critical role for PKCα signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors p21 and p27 and activation of Akt and ERK dependent proliferative pathways. Thus, targeting PKCα may provide novel therapeutic options in endometrial tumors. PMID:19672862

  9. ERβ1 inhibits the migration and invasion of breast cancer cells through upregulation of E-cadherin in a Id1-dependent manner

    International Nuclear Information System (INIS)

    Highlights: • Expression of ERβ1 was positively correlated with E-cadherin in breast cancer cell. • ERβ1 upregulates E-cadherin expression in breast cancer cell lines. • ERβ1 upregulates E-cadherin expression in a Id1-dependent manner. - Abstract: ERβ1 is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. It plays an important role in regulating the progression of breast cancer. However, the mechanisms of ERβ1 in tumorigenesis, metastasis and prognosis are still not fully clear. In this study, we showed that the expression of ERβ1 was positively correlated with E-cadherin expression in breast cancer cell lines. In addition, we found that ERβ1 upregulates E-cadherin expression in breast cancer cell lines. Furthermore, we also found that ERβ1 inhibits the migration and invasion of breast cancer cells and upregulated E-cadherin expression in a Id1-dependent manner. Taken together, our study provides further understanding of the molecular mechanism of ERβ1 in tumor metastasis and suggests the feasibility of developing novel therapeutic approaches to target Id1 to inhibit breast cancer metastasis

  10. ERβ1 inhibits the migration and invasion of breast cancer cells through upregulation of E-cadherin in a Id1-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing (China); Ming, Jia [Department of Breast, Thyroid and Pancreas Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing (China); Xu, Yan [Department of Breast and Thyroid Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing (China); Zhang, Yi, E-mail: zy53810@163.com [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing (China); Jiang, Jun, E-mail: Jcbd@medmail.com.cn [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing (China)

    2015-02-06

    Highlights: • Expression of ERβ1 was positively correlated with E-cadherin in breast cancer cell. • ERβ1 upregulates E-cadherin expression in breast cancer cell lines. • ERβ1 upregulates E-cadherin expression in a Id1-dependent manner. - Abstract: ERβ1 is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. It plays an important role in regulating the progression of breast cancer. However, the mechanisms of ERβ1 in tumorigenesis, metastasis and prognosis are still not fully clear. In this study, we showed that the expression of ERβ1 was positively correlated with E-cadherin expression in breast cancer cell lines. In addition, we found that ERβ1 upregulates E-cadherin expression in breast cancer cell lines. Furthermore, we also found that ERβ1 inhibits the migration and invasion of breast cancer cells and upregulated E-cadherin expression in a Id1-dependent manner. Taken together, our study provides further understanding of the molecular mechanism of ERβ1 in tumor metastasis and suggests the feasibility of developing novel therapeutic approaches to target Id1 to inhibit breast cancer metastasis.

  11. SHOX2 Is a Direct miR-375 Target and a Novel Epithelial-to-Mesenchymal Transition Inducer in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sungguan Hong

    2014-04-01

    Full Text Available MicroRNAs have added a new dimension to our understanding of tumorigenesis and associated processes like epithelial-to-mesenchymal transition (EMT. Here, we show that miR-375 is elevated in epithelial-like breast cancer cells, and ectopic miR-375 expression suppresses EMT in mesenchymal-like breast cancer cells. We identified short stature homeobox 2 (SHOX2 as a miR-375 target, and miR-375–mediated suppression in EMT was reversed by forced SHOX2 expression. Ectopic SHOX2 expression can induce EMT in epithelial-like breast cancer cells, whereas SHOX2 knockdown diminishes EMT traits in mesenchymal-like breast cancer cells, demonstrating SHOX2 as an EMT inducer. We show that SHOX2 acts as a transcription factor to upregulate transforming growth factor β receptor I (TβR-I expression, and TβR-I inhibitor LY364947 abolishes EMT elicited by ectopic SHOX2 expression, suggesting that transforming growth factor β signaling is essential for SHOX2-induced EMT. Manipulating SHOX2 abundance in breast cancer cells impact in vitro invasion and in vivo dissemination. Analysis of breast tumor microarray database revealed that high SHOX2 expression significantly correlates with poor patient survival. Our study supports a critical role of SHOX2 in breast tumorigenicity.

  12. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    International Nuclear Information System (INIS)

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80+ macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206+ TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer

  13. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang, E-mail: zgliu@helix.nih.gov [Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-04

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80{sup +} macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206{sup +} TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

  14. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2013-12-01

    Full Text Available Tumor-associated macrophages (TAMs promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA blocks occurrence of tumor associated macrophages (TAMs in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA, a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80+ macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206+ TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

  15. TR4 nuclear receptor functions as a tumor suppressor for prostate tumorigenesis via modulation of DNA damage/repair system.

    Science.gov (United States)

    Lin, Shin-Jen; Lee, Soo Ok; Lee, Yi-Fen; Miyamoto, Hiroshi; Yang, Dong-Rong; Li, Gonghui; Chang, Chawnshang

    2014-06-01

    Testicular nuclear receptor 4 (TR4), a member of the nuclear receptor superfamily, plays important roles in metabolism, fertility and aging. The linkage of TR4 functions in cancer progression, however, remains unclear. Using three different mouse models, we found TR4 could prevent or delay prostate cancer (PCa)/prostatic intraepithelial neoplasia development. Knocking down TR4 in human RWPE1 and mouse mPrE normal prostate cells promoted tumorigenesis under carcinogen challenge, suggesting TR4 may play a suppressor role in PCa initiation. Mechanism dissection in both in vitro cell lines and in vivo mice studies found that knocking down TR4 led to increased DNA damage with altered DNA repair system that involved the modulation of ATM expression at the transcriptional level, and addition of ATM partially interrupted the TR4 small interfering RNA-induced tumorigenesis in cell transformation assays. Immunohistochemical staining in human PCa tissue microarrays revealed ATM expression is highly correlated with TR4 expression. Together, these results suggest TR4 may function as a tumor suppressor to prevent or delay prostate tumorigenesis via regulating ATM expression at the transcriptional level. PMID:24583925

  16. Early breast cancer

    International Nuclear Information System (INIS)

    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.)

  17. Pregnancy After Breast Cancer.

    Science.gov (United States)

    Gemignani; Petrek

    1999-05-01

    BACKGROUND: The issue of pregnancy following the diagnosis and treatment of breast cancer is important because the incidence of breast cancer is increasing in women of childbearing age. The fact that many women are delaying childbearing, whether for educational, professional, or personal reasons, increases the number of women who will undergo breast cancer treatment before completing childbearing. METHODS: Data on pregnancy in breast cancer survivors are limited and consist only of retrospective data. This paper reviews the published literature on the influence of subsequent pregnancy on breast cancer, including three recent large-scale population-based studies. RESULTS: The survival of women with breast carcinoma who subsequently become pregnant is not reported to be decreased in any of the published series. However, several biases may be present that justify the concern regarding the conclusions. CONCLUSIONS: Further research on the safety of subsequent pregnancy after breast carcinoma treatment is needed. To address these issues, patients are currently being accrued for a large, prospective, multicenter study of young breast carcinoma patients. PMID:10758557

  18. Types of Breast Pumps

    Science.gov (United States)

    ... breast-shield. Some experts discourage the use of bicycle horn pumps because they may be difficult to clean and dry. Battery-Powered and Electric Pumps A powered breast pump uses batteries or a cord plugged into an electrical outlet to power a small motorized pump that ...

  19. Inflammatory Breast Cancer

    Science.gov (United States)

    ... breast cancer: consensus statement for standardized diagnosis and treatment. Annals of Oncology 2011; 22(3):515-523. [PubMed Abstract] Fouad TM, Kogawa T, Reuben JM, Ueno NT. The role of inflammation in inflammatory breast cancer. Advances in Experimental Medicine and Biology 2014; 816:53-73. [PubMed ...

  20. Relationship between histology, development and tumorigenesis of mammary gland in female rat.

    Science.gov (United States)

    Líška, Ján; Brtko, Július; Dubovický, Michal; Macejová, Dana; Kissová, Viktória; Polák, Štefan; Ujházy, Eduard

    2016-02-14

    The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential. PMID:26424555

  1. A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis

    OpenAIRE

    Chen, Qian; Zhang, Nailing; Gray, Ryan S.; Li, Huili; Ewald, Andrew J.; Zahnow, Cynthia A.; Pan, Duojia

    2014-01-01

    In this study, Chen et al. discover that the Hippo pathway is functionally dispensable in virgin mammary glands but specifically required during pregnancy. YAP hyperactivation in mammary epithelia leads to defects in terminal differentiation. Loss of YAP causes no obvious defects in virgin mammary glands but potently suppresses oncogene-induced mammary tumors. This selective requirement for YAP in oncogenic growth suggests YAP inhibitors as targeted therapies against breast cancers.

  2. Gossypiboma after Breast Augmentation

    Directory of Open Access Journals (Sweden)

    Kira Lundin

    2013-01-01

    Full Text Available A 39-year-old woman was referred for removal of cosmetic breast implants and related siliconoma. After an exchange of breast implants at a private clinic a year previously, she had asymmetry of the right breast, persistent pain, and a generally unacceptable cosmetic result. An MRI had shown a well-defined area with spots of silicone-like material at the upper pole of the right breast. Surgical removal of presumed silicone-imbibed breast tissue was undertaken, and surprisingly a gossypiboma was found in its place, which had not been identified on the MRI. Gossypiboma is the condition of an accidentally retained surgical sponge. This complication is also known as a textiloma, gauzoma, or muslinoma and is well described in other surgical specialties. However, it is extremely rare after plastic surgery, and this case illustrates the need for continued attention to the surgical count of sponges and instruments.

  3. Investigation of single-strand conformational polymorphism of the TP53 gene in women with a family history of breast cancer

    Directory of Open Access Journals (Sweden)

    R.R. Burbano

    2000-11-01

    Full Text Available Breast cancer in families with germ line mutations in the TP53 gene has been described in the medical literature. Mutation screening for susceptibility genes should allow effective prophylactic and preventive measures. Using single-strand conformational polymorphism, we screened for mutations in exons 5, 6, 7 and 8 of gene TP53 in the peripheral blood of 8 young non-affected members (17 to 36 years old of families with a history of breast cancer. Studies of this type on young patients (mean age, 25 years are very rare in the literature. The identification of these mutations would contribute to genetic counseling of members of families with predisposition to breast cancer. The results obtained did not show any polymorphism indicating mutation. In our sample, the familial tumorigenesis is probably related to other gene etiologies.

  4. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Balance › Breast Cancer and Bone Loss Fact Sheet Breast Cancer and Bone Loss July, 2010 Download PDFs English ... JoAnn Pinkerton, MD What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  5. Vegetable Seed Industry Mode of Holland and Revelation%荷兰蔬菜种业模式及启示

    Institute of Scientific and Technical Information of China (English)

    李艳军; 李万君

    2012-01-01

    The development situation of vegetable seed industry of Holland was briefly introduced at first, then the mode and its characteristics were analyzed, with the large-scale seed company as the leader, taking innovation and specialization as fundamental, demand oriented, total quality management, the strict protection of intellectual property, powerful and perfect circulation system as well as government exerting service functions well, and so on. At last, some revelations to China's vegetable seed industry development through comparing it with Dutch vegetable seed industry mode were got.%对荷兰蔬菜种业发展状况作了简要介绍,总结了荷兰蔬菜种业的运营模式,并详细分析了其特点:以大型种业集团为龙头、以创新和专业化为根本、以需求为导向、全面实行质量管理、严格的知识产权保护、强大而完善的流通体系以及政府充分行使服务职能等.通过对比分析,得出荷兰蔬菜种业运营模式对我国蔬菜种业发展的几点启示.

  6. 欧洲主权债务危机:缘起、原因及启示%European Sovereign Debt Crises: Origin, Reasons and Revelations

    Institute of Scientific and Technical Information of China (English)

    张钦朋

    2012-01-01

    European sovereign debt crisis is the continuation and deepening of the international financial crisis, bringing uncertainty to European countries and the world economic recovery. European sovereign debt crisis is the result of the combined effects of the contradiction of capitalism, financial crisis impact, institution- al and structural deficiencies, policy failure and other factors. It reflects the inherent contradictions of the cap- italist economic system. European sovereign debt crisis has some revelations to China's macroeconomic policy.%欧洲主权债务危机是国际金融危机的延续和深化,给欧洲国家乃至世界的经济复苏带来不确定性。欧债危机是资本主义矛盾、金融危机冲击、制度性和结构性缺陷、政策失灵等因素综合作用的结果,反映了资本主义经济体系的内在矛盾。欧债危机对我国宏观政策具有一定的启示作用。

  7. 杜威实用主义哲学的司法启示%Judicial Revelation of Dewey’s Pragmatism

    Institute of Scientific and Technical Information of China (English)

    张式泽

    2015-01-01

    杜威实用主义哲学体系中包含着重视科学方法、重视行动与变化、拒斥绝对论和重视效用性等重要思想。这些思想对于解决我国立法与司法的冲突及脱节等问题上具有重要启示,完成从法律本位到问题本位的转变则是目前司法所要解决的问题。%Dewey’s Pragmatism contains some important thoughts which include the emphasis on scientific methods,attention to op⁃erations in the philosophical system with changes in the absolute rejection of the important thoughts on the usefulness and importance and so on. These ideas for solving the country’s legislative and judicial issues such as conflict and disconnection has an important revelation, completing the transition from the legal standard to the problem.

  8. Role of N-acetylgalactosaminyltransferase 6 in early tumorigenesis and formation of metastasis.

    Science.gov (United States)

    Liesche, Friederike; Kölbl, Alexandra C; Ilmer, Matthias; Hutter, Stefan; Jeschke, Udo; Andergassen, Ulrich

    2016-05-01

    Glycosylation is one of the most important posttranslational modifications of proteins and lipids that contributes to the structural diversity of cellular molecules. Enzymes of the glycosyltransferase class are responsible for altering glycosylation patterns by adding carbohydrate chains to the respective acceptor molecules. It is well known that glycosylation is commonly altered in cancerous tissue. Therefore, the present study aimed to determine the incidence of N‑acetylgalactosaminyltransferase 6 (GALNT6), a prominent member of the glycosyltransferase class, in breast cancer tissue of different developmental stages by immunohistochemistry. Although no correlation was identified between tumour characteristics and GALNT6 staining intensity, to the best of our knowledge, this is the first study to demonstrate that tissue from carcinoma in situ‑tumours and metastases were more heavily stained than late‑stage breast cancers. This may indicate an important role of glycosylation aberration in escaping the immune system at early phases of tumour development. The present study also hypothesised that nascent or early metastasizing tumours are normally recognized by the immune system of the patient, but glycosylation pattern changes may facilitate tumor escape from immune recognition. In follow‑up studies, our group will aim to confirm and consolidate these results in a larger patient cohort that may give greater insight into breast cancer characterization as well as tumour treatment. PMID:27035742

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

    International Nuclear Information System (INIS)

    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

  10. RhoC impacts the metastatic potential and abundance of breast cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Devin T Rosenthal

    Full Text Available Cancer stem cells (CSCs have been shown to promote tumorigenesis of many tumor types, including breast, although their relevance to cancer metastasis remains unclear. While subpopulations of CSCs required for metastasis have been identified, to date there are no known molecular regulators of breast CSC (BCSC metastasis. Here we identify RhoC GTPase as an important regulator of BCSC metastasis, and present evidence suggesting that RhoC also modulates the frequency of BCSCs within a population. Using an orthotopic xenograft model of spontaneous metastasis we discover that RhoC is both necessary and sufficient to promote SUM149 and MCF-10A BCSC metastasis--often independent from primary tumor formation--and can even induce metastasis of non-BCSCs within these cell lines. The relationship between RhoC and BCSCs persists in breast cancer patients, as expression of RhoC and the BCSC marker ALDH1 are highly correlated in clinical specimens. These results suggest new avenues to combating the deadliest cells driving the most lethal stage of breast cancer progression.

  11. Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling.

    Science.gov (United States)

    Bao, Cheng; Kim, Min Chae; Chen, Jing; Song, Jieun; Ko, Hyuk Wan; Lee, Hong Jin

    2016-07-13

    Although inhibition of mammary tumorigenesis by isothiocyanates has been widely studied, little is known about the effects of sulforaphene on invasiveness of breast cancer. Here, sulforaphene significantly inhibited the migration and invasion of triple-negative SUM159 human breast cancer cells and suppressed the expression and activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). The Hedgehog (Hh) pathway, as an upstream signaling modulator, was significantly suppressed by sulforaphene. In particular, ciliary localization of Gli1 and its nuclear translocation were blocked by sulforaphene in a time-dependent manner. Consistently, downregulation of Hh signaling by vismodegib and Gli1 knockdown reduced the cellular migration and invasion as well as the expression of MMP-2 and MMP-9. These results indicate that the suppression of Hh/Gli1 signaling by sulforaphene may reduce the MMP-2 and MMP-9 activities and cellular invasiveness of human breast cancer cells, suggesting the potential efficacy of sulforaphene against breast cancer invasion and metastasis. PMID:27327035

  12. Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis

    Science.gov (United States)

    Perez-Janices, Noemi; Blanco-Luquin, Idoia; Torrea, Natalia; Liechtenstein, Therese; Escors, David; Cordoba, Alicia; Vicente-Garcia, Francisco; Jauregui, Isabel; De La Cruz, Susana; Illarramendi, José Juan; Coca, Valle; Berdasco, Maria; Kochan, Grazyna; Ibañez, Berta; Lera, José Miguel; Guerrero-Setas, David

    2015-01-01

    Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2′-deoxycytidine in the re-expression of these genes was examined in triple-negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors (p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple-negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis (P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer. PMID:26284587

  13. Clinical evidence of the efficacy of everolimus and its potential in the treatment of breast cancer

    Directory of Open Access Journals (Sweden)

    Saksena R

    2013-05-01

    Full Text Available Rujuta Saksena, Serena T WongThe Cancer Institute of New Jersey, New Brunswick, NJ, USAAbstract: The PI3K/Akt/mTOR (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway regulates several key cellular functions and its dysregulation creates an environment that promotes tumorigenesis as well as resistance to therapy. The mTOR inhibitor everolimus has emerged as a promising agent in the treatment of breast cancer and was recently approved in combination with exemestane for advanced hormone receptor–positive disease after progression on a nonsteroidal aromatase inhibitor. Everolimus may also be effective in combination with cytotoxic and human epidermal growth factor receptor-2-directed therapies for the treatment of other subtypes of breast cancer. This paper highlights preclinical and clinical data that have emerged on the role of mTOR inhibition in breast cancer. Although generally well tolerated, everolimus carries a unique side effect profile of which both patients and providers should be made aware. Recommendations related to the administration of everolimus in the clinical setting are also discussed.Keywords: everolimus, breast cancer, mTOR inhibition

  14. Study on interleukin-18 gene transfer into human breast cancer cells to prevent tumorigenicity

    Institute of Scientific and Technical Information of China (English)

    韩明勇; 郑树; 于金明; 彭佳萍; 郭其森; 王家林

    2004-01-01

    To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37, human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418. The biological expression of rhIL-18 was tested by RT-PCR and ELISA method; nude mice were injected with Bcap37 cell with or without the hIL-18 gene. The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3±4.5 pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth. These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine; the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity. The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.

  15. The nucleolar size is associated to the methylation status of ribosomal DNA in breast carcinomas

    International Nuclear Information System (INIS)

    There is a body of evidence that shows a link between tumorigenesis and ribosome biogenesis. The precursor of mature 18S, 28S and 5.8S ribosomal RNAs is transcribed from the ribosomal DNA gene (rDNA), which exists as 300–400 copies in the human diploid genome. Approximately one half of these copies are epigenetically silenced, but the exact role of epigenetic regulation on ribosome biogenesis is not completely understood. In this study we analyzed the methylation profiles of the rDNA promoter and of the 5’ regions of 18S and 28S in breast cancer. We analyzed rDNA methylation in 68 breast cancer tissues of which the normal counterpart was partially available (45/68 samples) using the MassARRAY EpiTYPER assay, a sensitive and quantitative method with single base resolution. We found that rDNA locus tended to be hypermethylated in tumor compared to matched normal breast tissues and that the DNA methylation level of several CpG units within the rDNA locus was associated to nuclear grade and to nucleolar size of tumor tissues. In addition we identified a subgroup of samples in which large nucleoli were associated with very limited or absent rDNA hypermethylation in tumor respect to matched normal tissue. In conclusion, we suggest that rDNA is an important target of epigenetic regulation in breast tumors and that rDNA methylation level is associated to nucleolar size

  16. Comparison of genomic abnormalities between BRCAX and sporadic breast cancers studied by comparative genomic hybridization.

    Science.gov (United States)

    Gronwald, Jacek; Jauch, Anna; Cybulski, Cezary; Schoell, Brigitte; Böhm-Steuer, Barbara; Lener, Marcin; Grabowska, Ewa; Górski, Bohdan; Jakubowska, Anna; Domagała, Wenancjusz; Chosia, Maria; Scott, Rodney J; Lubiński, Jan

    2005-03-20

    Very little is known about the chromosomal regions harbouring genes involved in initiation and progression of BRCAX-associated breast cancers. We applied comparative genomic hybridization (CGH) to identify the most frequent genomic imbalances in 18 BRCAX hereditary breast cancers and compared them to chromosomal aberrations detected in a group of 27 sporadic breast cancers. The aberrations observed most frequently in BRCAX tumours were gains of 8q (83%), 19q (67%), 19p (61%), 20q (61%), 1q (56%), 17q (56%) and losses of 8p (56%), 11q (44%) and 13q (33%). The sporadic cases most frequently showed gains of 1q (67%), 8q (48%), 17q (37%), 16p (33%), 19q (33%) and losses of 11q (26%), 8p (22%) and 16q (19%). Losses of 8p and gains 8q, 19 as well as gains of 20q (with respect to ductal tumours only) were detected significantly more often in BRCAX than in sporadic breast cancers. Analysis of 8p-losses and 8q-gains showed that these aberrations are early events in the tumorigenesis of BRCAX tumors. The findings of this report indicate similarities between BRCAX and BRCA2 tumours, possibly suggesting a common pathway of disease. These findings need confirmation by more extensive studies because only a limited number of cases were analysed and there are relatively few reports published. PMID:15540206

  17. High expression of KIF26B in breast cancer associates with poor prognosis.

    Science.gov (United States)

    Wang, Qun; Zhao, Zong-Bin; Wang, Geng; Hui, Zhen; Wang, Ming-Hua; Pan, Jun-Feng; Zheng, Hong

    2013-01-01

    To date, a great number of studies have demonstrated that altered expression of kinesins is associated with development and progression of various human cancers. Kinesin family member 26B (KIF26B), a member of the kinesin superfamily proteins (KIFs), is essential for kidney development. However, the role of KIF26B during tumorigenesis and progression is limited. Here, we demonstrate that both KIF26B mRNA and protein are overexpression in breast cancer tissues by RT-qPCR and western blot. Immunohistochemistry revealed that KIF26B expression significantly correlated with clinicopathological factors, including tumor size (P = 0.011), grade (P = 0.017), lymph node status (P = 0.009) and ER status (P = 0.012). Moreover, the Kaplan-Meier analysis indicated that breast cancer patients with high KIF26B expression had a shorter survival than those with low KIF26B expression. In addition, multivariate analysis indicated that KIF26B is an independent prognostic for outcome in breast cancer (HR, 2.356; 95%CI, 1.268-4.378; P = 0.007). Collectively, our study demonstrated that KIF26B was overexpression in breast cancer and could be served as a potential prognostic marker. PMID:23585914

  18. Ultrasound characterization of breast masses

    International Nuclear Information System (INIS)

    A lump in the breast is a cause of great concern. High frequency, high-resolution USG helps in its evaluation. This is exemplified in women with dense breast tissue where USG is useful in detecting small breast cancers that are not seen on mammography. Several studies in the past have addressed the issue of differentiating benign from malignant lesions in the breast. The American College of Radiology has also brought out a BIRADS-US classification system for categorizing focal breast lesions

  19. Oncoplastic breast surgery in Denmark

    DEFF Research Database (Denmark)

    Klit, Anders; Henriksen, Trine Foged; Siersen, Hans Erik;

    2014-01-01

    With improved survival rates after breast cancer treatment, more attention is drawn to improve the cosmetic outcome after surgical treatment of breast cancer. In this process the oncoplastic breast surgery was conceived. It supplements the traditional surgical treatments (mastectomy and breast...... conserving surgery) with increased focus on individualized therapy. The ambition is to obtain the best possible cosmetic outcome without compromising recurrence rates and survival. This article provides an overview of the current oncoplastic breast surgery treatment offered in Denmark....

  20. Tyrosine phosphatase Shp2 mediates the estrogen biological action in breast cancer via interaction with the estrogen extranuclear receptor.

    Directory of Open Access Journals (Sweden)

    Jun Li

    Full Text Available The extranuclear estrogen receptor pathway opens up novel perspectives in many physiological and pathological processes, especially in breast carcinogenesis. However, its function and mechanisms are not fully understood. Herein we present data identifying Shp2, a SH2-containing tyrosine phosphatase, as a critical component of extranuclear ER pathway in breast cancer. The research checked that the effect of Shp2 on the tumor formation and growth in animal model and investigated the regulation of Shp2 on the bio-effect and signaling transduction of estrogen in breast cancer cell lines. The results showed that Shp2 was highly expressed in more than 60% of total 151 breast cancer cases. The inhibition of Shp2 activity by PHPS1 (a Shp2 inhibitor delayed the development of dimethylbenz(aanthracene (DMBA-induced tumors in the rat mammary gland and also blocked tumor formation in MMTV-pyvt transgenic mice. Estradiol (E2 stimulated protein expression and phosphorylation of Shp2, and induced Shp2 binding to ERα and IGF-1R around the membrane to facilitate the phosphorylation of Erk and Akt in breast cancer cells MCF7. Shp2 was also involved in several biological effects of the extranuclear ER-initiated pathway in breast cancer cells. Specific inhibitors (phps1, phps4 and NSC87877 or small interference RNAs (siRNA of Shp2 remarkably suppressed E2-induced gene transcription (Cyclin D1 and trefoil factor 1 (TFF1, rapid DNA synthesis and late effects on cell growth. These results introduced a new mechanism for Shp2 oncogenic action and shed new light on extranuclear ER-initiated action in breast tumorigenesis by identifying a novel associated protein, Shp2, for extranuclear ER pathway, which might benefit the therapy of breast cancer.

  1. Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

    Science.gov (United States)

    2016-03-17

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  2. Herpesviruses and breast milk

    Directory of Open Access Journals (Sweden)

    C. Pietrasanta

    2014-06-01

    Full Text Available Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV and cytomegalovirus (CMV, herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections are conditions during which breastfeeding may be temporarily contraindicated, but expressed breast milk should always be given to the infant. CMV infection acquired through breast milk rarely causes disease in healthy term newborns; an increased risk of CMV disease has been documented in preterm infants. However, the American Academy of Pediatrics (AAP does not regard maternal CMV seropositivity as a contraindication to breastfeeding; according to the AAP, in newborns weighing less than 1500 g, the decision should be taken after weighing the benefits of breast milk against the risk of transmission of infection. The real efficacy of the different methods of inactivating CMV in breast milk should be compared in controlled clinical trials, rigorously examining the negative consequences that each of these methods can have on the immunological and nutritional properties of the milk itself, with a view to establish the best risk-benefit ratio of these strategies before they are recommended for use in clinical practice.

  3. Ulipristal Acetate Inhibits Progesterone Receptor Isoform A-Mediated Human Breast Cancer Proliferation and BCl2-L1 Expression.

    Directory of Open Access Journals (Sweden)

    Nathalie Esber

    Full Text Available The progesterone receptor (PR with its isoforms and ligands are involved in breast tumorigenesis and prognosis. We aimed at analyzing the respective contribution of PR isoforms, PRA and PRB, in breast cancer cell proliferation in a new estrogen-independent cell based-model, allowing independent PR isoforms analysis. We used the bi-inducible human breast cancer cell system MDA-iPRAB. We studied the effects and molecular mechanisms of action of progesterone (P4 and ulipristal acetate (UPA, a new selective progesterone receptor modulator, alone or in combination. P4 significantly stimulated MDA-iPRA expressing cells proliferation. This was associated with P4-stimulated expression of the anti-apoptotic factor BCL2-L1 and enhanced recruitment of PRA, SRC-1 and RNA Pol II onto the +58 kb PR binding motif of the BCL2-L1 gene. UPA decreased cell proliferation and repressed BCL2-L1 expression in the presence of PRA, correlating with PRA and SRC1 but not RNA Pol II recruitment. These results bring new information on the mechanism of action of PR ligands in controlling breast cancer cell proliferation through PRA in an estrogen independent model. Evaluation of PR isoforms ratio, as well as molecular signature studies based on PRA target genes could be proposed to facilitate personalized breast cancer therapy. In this context, UPA could be of interest in endocrine therapy. Further confirmation in the clinical setting is required.

  4. Ulipristal Acetate Inhibits Progesterone Receptor Isoform A-Mediated Human Breast Cancer Proliferation and BCl2-L1 Expression.

    Science.gov (United States)

    Esber, Nathalie; Le Billan, Florian; Resche-Rigon, Michèle; Loosfelt, Hugues; Lombès, Marc; Chabbert-Buffet, Nathalie

    2015-01-01

    The progesterone receptor (PR) with its isoforms and ligands are involved in breast tumorigenesis and prognosis. We aimed at analyzing the respective contribution of PR isoforms, PRA and PRB, in breast cancer cell proliferation in a new estrogen-independent cell based-model, allowing independent PR isoforms analysis. We used the bi-inducible human breast cancer cell system MDA-iPRAB. We studied the effects and molecular mechanisms of action of progesterone (P4) and ulipristal acetate (UPA), a new selective progesterone receptor modulator, alone or in combination. P4 significantly stimulated MDA-iPRA expressing cells proliferation. This was associated with P4-stimulated expression of the anti-apoptotic factor BCL2-L1 and enhanced recruitment of PRA, SRC-1 and RNA Pol II onto the +58 kb PR binding motif of the BCL2-L1 gene. UPA decreased cell proliferation and repressed BCL2-L1 expression in the presence of PRA, correlating with PRA and SRC1 but not RNA Pol II recruitment. These results bring new information on the mechanism of action of PR ligands in controlling breast cancer cell proliferation through PRA in an estrogen independent model. Evaluation of PR isoforms ratio, as well as molecular signature studies based on PRA target genes could be proposed to facilitate personalized breast cancer therapy. In this context, UPA could be of interest in endocrine therapy. Further confirmation in the clinical setting is required. PMID:26474308

  5. The cyclin-like protein Spy1/RINGO promotes mammary transformation and is elevated in human breast cancer

    International Nuclear Information System (INIS)

    Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis. Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation. We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. Importantly, we show for the first time that enhanced levels of Spy1 protein are found in a large number of human breast cancers and that knockdown of Spy1 impairs breast cancer cell proliferation. Collectively, this work supports that Spy1 is a unique activator of Cdk1 in breast cancer cells and may represent a valuable drug target and/or a prognostic marker for subsets of breast cancers

  6. Knockout and transgenic mice of Trp53: what have we learned about p53 in breast cancer?

    International Nuclear Information System (INIS)

    The human p53 tumor suppressor gene TP53 is mutated at a high frequency in sporadic breast cancer, and Li-Fraumeni syndrome patients who carry germline mutations in one TP53 allele have a high incidence of breast cancer. In the 10 years since the first knockout of the mouse p53 tumor suppressor gene (designated Trp53) was published, much has been learned about the contribution of p53 to biology and tumor suppression in the breast through the use of p53 transgenic and knockout mice. The original mice deficient in p53 showed no mammary gland phenotype. However, studies using BALB/c-Trp53-deficient mice have demonstrated a delayed involution phenotype and a mammary tumor phenotype. Together with other studies of mutant p53 transgenes and p53 bitransgenics, a greater understanding has been gained of the role of p53 in involution, of the regulation of p53 activity by hormones, of the effect of mouse strain and modifier genes on tumor phenotype, and of the cooperation between p53 and other oncogenic pathways, chemical carcinogens and hormonal stimulation in mammary tumorigenesis. Both p53 transgenic and knockout mice are important in vivo tools for understanding breast cancer, and are yet to be exploited for developing therapeutic strategies in breast cancer

  7. Cholinergic muscarinic receptor activation augments murine intestinal epithelial cell proliferation and tumorigenesis

    International Nuclear Information System (INIS)

    Previously, we showed that M3 muscarinic receptor (M3R; gene name Chrm3) deficiency attenuates murine intestinal neoplasia, supporting the hypothesis that muscarinic receptors play an important role in intestinal tumorigenesis. To test this hypothesis, in the present study we treated mice with bethanechol, a non-selective muscarinic receptor agonist without nicotinic receptor activity, and examined its effects on azoxymethane (AOM)-induced colon neoplasia. Mice were provided with drinking water containing 400 μg/mL bethanechol chloride or water without additions (control) for a total of 20 weeks, a period that included the initial 6 weeks when mice received intraperitoneal injections of AOM. When euthanized at week 20, control mice had 8.0 ± 1.3 tumors per animal, whereas bethanechol-treated mice had 10.4 ± 1.5 tumors per mouse (mean ± SE; P = 0.023), a 30% increase. Strikingly, tumor volume per animal was increased 52% in bethanechol-treated compared with control mice (179.7 ± 21.0 vs. 111. 8 ± 22.4 mm3; P = 0.047). On histological examination, bethenechol-treated mice also had more adenocarcinomas per animal (8.0 ± 1.0 vs. 4.1 ± 0.6 for control mice, P = 0.0042). Cell proliferation in both normal mucosa and adenocarcinomas was increased in bethanechol-treated compared to control mice. Also, in tumors, bethanechol treatment increased expression of Chrm3, Egfr and post-Egfr signaling molecules Myc and cyclin D1. Bethanechol treatment increased the thickness of normal colonic mucosa and the expression of selected matrix metalloproteinase (Mmp) genes, including Mmp7, Mmp10 and Mmp13. These findings support a prominent role for muscarinic receptors in colon neoplasia, and identify post-receptor signaling molecules as potential therapeutic targets

  8. Zebrafish neurofibromatosis type 1 genes have redundant functions in tumorigenesis and embryonic development

    Directory of Open Access Journals (Sweden)

    Jimann Shin

    2012-11-01

    Neurofibromatosis type 1 (NF1 is a common, dominantly inherited genetic disorder that results from mutations in the neurofibromin 1 (NF1 gene. Affected individuals demonstrate abnormalities in neural-crest-derived tissues that include hyperpigmented skin lesions and benign peripheral nerve sheath tumors. NF1 patients also have a predisposition to malignancies including juvenile myelomonocytic leukemia (JMML, optic glioma, glioblastoma, schwannoma and malignant peripheral nerve sheath tumors (MPNSTs. In an effort to better define the molecular and cellular determinants of NF1 disease pathogenesis in vivo, we employed targeted mutagenesis strategies to generate zebrafish harboring stable germline mutations in nf1a and nf1b, orthologues of NF1. Animals homozygous for loss-of-function alleles of nf1a or nf1b alone are phenotypically normal and viable. Homozygous loss of both alleles in combination generates larval phenotypes that resemble aspects of the human disease and results in larval lethality between 7 and 10 days post fertilization. nf1-null larvae demonstrate significant central and peripheral nervous system defects. These include aberrant proliferation and differentiation of oligodendrocyte progenitor cells (OPCs, dysmorphic myelin sheaths and hyperplasia of Schwann cells. Loss of nf1 contributes to tumorigenesis as demonstrated by an accelerated onset and increased penetrance of high-grade gliomas and MPNSTs in adult nf1a+/−; nf1b−/−; p53e7/e7 animals. nf1-null larvae also demonstrate significant motor and learning defects. Importantly, we identify and quantitatively analyze a novel melanophore phenotype in nf1-null larvae, providing the first animal model of the pathognomonic pigmentation lesions of NF1. Together, these findings support a role for nf1a and nf1b as potent tumor suppressor genes that also function in the development of both central and peripheral glial cells as well as melanophores in zebrafish.

  9. Gene expression in human thyrocytes and autonomous adenomas reveals suppression of negative feedbacks in tumorigenesis

    Science.gov (United States)

    van Staveren, Wilma C. G.; Solís, David Weiss; Delys, Laurent; Venet, David; Cappello, Matteo; Andry, Guy; Dumont, Jacques E.; Libert, Frédérick; Detours, Vincent; Maenhaut, Carine

    2006-01-01

    The cAMP signaling pathway regulates growth of many cell types, including somatotrophs, thyrocytes, melanocytes, ovarian follicular granulosa cells, adrenocortical cells, and keratinocytes. Mutations of partners from the cAMP signaling cascade are involved in tumor formation. Thyroid-stimulating hormone (TSH) receptor and Gsα activating mutations have been detected in thyroid autonomous adenomas, Gsα mutations in growth hormone-secreting pituitary adenomas, and PKAR1A mutations in Carney complex, a multiple neoplasia syndrome. To gain more insight into the role of cAMP signaling in tumor formation, human primary cultures of thyrocytes were treated for different times (1.5, 3, 16, 24, and 48 h) with TSH to characterize modulations in gene expression using cDNA microarrays. This kinetic study showed a clear difference in expression, early (1.5 and 3 h) and late (16–48 h) after the onset of TSH stimulation. This result suggests a progressive sequential process leading to a change of cell program. The gene expression profile of the long-term stimulated cultures resembled the autonomous adenomas, but not papillary carcinomas. The molecular phenotype of the adenomas thus confirms the role of long-term stimulation of the TSH–cAMP cascade in the pathology. TSH induced a striking up-regulation of different negative feedback modulators of the cAMP cascade, presumably insuring the one-shot effect of the stimulus. Some were down- or nonregulated in adenomas, suggesting a loss of negative feedback control in the tumors. These results suggest that in tumorigenesis, activation of proliferation pathways may be complemented by suppression of multiple corresponding negative feedbacks, i.e., specific tumor suppressors. PMID:16381821

  10. Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Kumar Anupam; Chatopadhyay Tusharkant; Siddhartha Datta Gupta; Ralhan Ranju

    2006-01-01

    AIM: Disabled-2 (D4B2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein.METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specific PCR.RESULTS: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (Ptrend < 0.001).Promoter hypermethylation of DAB2 was observed in 2of 10 (20%) DAB2 immuno-negative ESCCs.CONCLUSION: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic gene silencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.

  11. Extensive metabolic disorders are present in APC(min) tumorigenesis mice.

    Science.gov (United States)

    Liu, Zhenzhen; Xiao, Yi; Zhou, Zhengxiang; Mao, Xiaoxiao; Cai, Jinxing; Xiong, Lu; Liao, Chaonan; Huang, Fulian; Liu, Zehao; Ali Sheikh, Md Sayed; Plutzky, Jorge; Huang, He; Yang, Tianlun; Duan, Qiong

    2016-05-15

    Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of β-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients. PMID:26948948

  12. Cooperation of the BTB-Zinc finger protein, Abrupt, with cytoskeletal regulators in Drosophila epithelial tumorigenesis

    Directory of Open Access Journals (Sweden)

    Nezaket Turkel

    2015-08-01

    Full Text Available The deregulation of cell polarity or cytoskeletal regulators is a common occurrence in human epithelial cancers. Moreover, there is accumulating evidence in human epithelial cancer that BTB-ZF genes, such as Bcl6 and ZBTB7A, are oncogenic. From our previous studies in the vinegar fly, Drosophila melanogaster, we have identified a cooperative interaction between a mutation in the apico-basal cell polarity regulator Scribble (Scrib and overexpression of the BTB-ZF protein Abrupt (Ab. Herein, we show that co-expression of ab with actin cytoskeletal regulators, RhoGEF2 or Src64B, in the developing eye-antennal epithelial tissue results in the formation of overgrown amorphous tumours, whereas ab and DRac1 co-expression leads to non-cell autonomous overgrowth. Together with ab, these genes affect the expression of differentiation genes, resulting in tumours locked in a progenitor cell fate. Finally, we show that the expression of two mammalian genes related to ab, Bcl6 and ZBTB7A, which are oncogenes in mammalian epithelial cancers, significantly correlate with the upregulation of cytoskeletal genes or downregulation of apico-basal cell polarity neoplastic tumour suppressor genes in colorectal, lung and other human epithelial cancers. Altogether, this analysis has revealed that upregulation of cytoskeletal regulators cooperate with Abrupt in Drosophila epithelial tumorigenesis, and that high expression of human BTB-ZF genes, Bcl6 and ZBTB7A, shows significant correlations with cytoskeletal and cell polarity gene expression in specific epithelial tumour types. This highlights the need for further investigation of the cooperation between these genes in mammalian systems.

  13. Intensity Modulated Accelerated Partial Breast Irradiation Before Surgery in Treating Older Patients With Hormone Responsive Stage 0-I Breast Cancer

    Science.gov (United States)

    2016-05-04

    Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Ductal Breast Carcinoma With Predominant Intraductal Component; Lobular Breast Carcinoma in Situ; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Tubular Ductal Breast Carcinoma

  14. Primary breast lymphoma in the right breast during treatment for left breast cancer

    OpenAIRE

    Fukuzawa Kengo; Kinoshita Tadahiko; Iwashita Yukio; Nishimura Ataru; Nagata Shigeyuki; Tashiro Hideya; Wakasugi Kenzo

    2007-01-01

    Abstract Background Primary breast lymphoma is a rare condition, and distinguishing it from breast cancer is important because their treatments differ radically. Moreover, a recent report showed that mastectomy offered no benefit in the treatment of primary breast lymphoma. Case presentation A 59-year-old woman was treated with adjuvant chemotherapy and local radiation after surgery for left breast cancer. She presented with a rapidly growing mass in the right breast at 20 months after surger...

  15. HEX expression and localization in normal mammary gland and breast carcinoma

    Directory of Open Access Journals (Sweden)

    Pandolfi Maura

    2006-07-01

    occurs during lactation and tumorigenesis, we suggest that HEX may play a role in differentiation of the epithelial breast cell.

  16. HER2 drives Mucin-like 1 to control proliferation in breast cancer cells

    Science.gov (United States)

    Conley, S J; Bosco, E E; Tice, D A; Hollingsworth, R E; Herbst, R; Xiao, Z

    2016-01-01

    Mucin-like 1 (MUCL1) was first identified as a breast-specific gene over a decade ago. Based on its highly restricted mRNA expression in breast tissue and continued expression during breast tumorigenesis and progression, MUCL1 is an attractive tumor-associated antigen and a potential therapeutic target. However, very little is known about the cellular location, biological functions and regulation of the MUCL1 protein, which will have a major impact on its druggability. Here we describe our efforts to fully characterize the cellular localization of MUCL1, investigate its regulation by key breast cancer oncogenes such as human epidermal growth factor receptor 2 (HER2) and discover its functional roles in breast cancer. Although some mucins are membrane bound, our data indicate that MUCL1 is secreted by some breast cancer cells, whereas others only express high levels of intracellular MUCL1. MUCL1 expression is highest in HER2-amplified breast tumors and inhibiting HER2 activity in tumor cells resulted in a decreased MUCL1 expression. In-depth investigation demonstrated that phosphoinositide3-kinase/Akt pathway, but not Ras/MEK pathway, controls MUCL1 expression downstream of HER2. Phenotypic assays revealed a strong dependence of HER2-positive cells on MUCL1 for cell proliferation. We further identified the mechanism by which MUCL1 regulates cell growth. Knockdown of MUCL1 induced a G1/S phase arrest concomitant with decreased cyclin D and increased p21 and p27 levels. Finally, we investigated the impact of MUCL1 loss on kinase signaling pathways in breast cancer cells through phospho-kinase array profiling. MUCL1 silencing abrogated phospho-focal adhesion kinase (FAK), Jun NH2-terminal kinase (JNK) and c-Jun signals, but not extracellular signal-regulated kinase or Akt pathway activities, thereby pointing to FAK/JNK pathway as the downstream effector of MUCL1 signaling. We are the first to identify an important role for MUCL1 in the proliferation of breast cancer

  17. β class II tubulin predominates in normal and tumor breast tissues

    International Nuclear Information System (INIS)

    Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs

  18. Transforming growth factor-β and breast cancer: Transforming growth factor-β/SMAD signaling defects and cancer

    International Nuclear Information System (INIS)

    Transforming growth factor-β (TGF-β) is a tumor suppressor, the function of which is compromised in many types of human cancer, including breast cancer. The tumor suppressive effects of TGF-β are caused by potent inhibition of cell proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative responses are mediated by a signaling system that includes two types of cell surface receptors and intracellular signal transducers, the SMAD proteins. Different molecular mechanisms can lead to loss of antiproliferative TGF-β responses in tumor cells, including mutations in components of the signaling system and inhibition of the SMAD signaling pathway by aberrant activities of various regulatory molecules. Some of these mechanisms will be discussed, with emphasis on their potential involvement in breast tumorigenesis

  19. Methylxanthines and breast cancer.

    Science.gov (United States)

    Schairer, C; Brinton, L A; Hoover, R N

    1987-10-15

    We investigated the relationship between methylxanthine consumption and breast cancer using data from a case-control study which included 1,510 cases and 1,882 controls identified through a nation-wide breast cancer screening program. There was no evidence of a positive association between methylxanthine consumption and risk of breast cancer. In fact, there was some suggestion of a negative association, particularly in women diagnosed after age 50. In addition, there was no evidence of increased risk with past or recent methylxanthine consumption, or with the consumption of caffeine or specific beverages, most notably brewed or instant caffeinated coffee and tea. PMID:3117709

  20. Actin—Towards a Deeper Understanding of the Relationship Between Tissue Context, Cellular Function and Tumorigenesis

    International Nuclear Information System (INIS)

    It is well-established that the actin cytoskeleton plays an important role in tumor development yet the contribution made by nuclear actin is ill-defined. In a recent study, nuclear actin was identified as a key mediator through which laminin type III (LN1) acts to control epithelial cell growth. In the breast, epithelial tumors are surrounded by an environment which lacks LN1. These findings point to actin as a potential mediator of tumor development. Here our current understanding of the roles of cytoplasmic and nuclear actin in normal and tumor cell growth is reviewed, relating these functions to cell phenotype in a tissue context

  1. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    MatthewJNaylor

    2013-08-01

    Full Text Available Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumours are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs. Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarise what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically.

  2. Breast cancer (metastatic)

    OpenAIRE

    Stebbing, Justin; Slater, Sarah; Slevin, Maurice

    2007-01-01

    Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered very unusual.

  3. Breast Problems in Women

    Science.gov (United States)

    ... compresses to the breast and gently expressing some milk may help. If you have an infection, talk to your doctor. He or she may give you an antibiotic. No 3. Did the tenderness start recently, and ...

  4. Using a Breast Pump

    Science.gov (United States)

    ... you can relax and not be disturbed while pumping. If you have an electric pump, find an ... otherwise irritating your nipple or breast tissue. Begin Pumping If your pump is electric or battery-powered, ...

  5. Living Beyond Breast Cancer

    Science.gov (United States)

    ... Prosthesis Complementary Therapy Types of Complementary Therapy Acupuncture Art Therapy Diet, Nutrition and Exercise Expressive Writing Guided ... SIGN UP FOR OUR MAILING LIST SIGN UP Facebook Twitter Instagram YouTube Living Beyond Breast Cancer Conference ...

  6. Breast Cancer Prevention

    Science.gov (United States)

    ... the risk of breast cancer: Having an abortion. Making diet changes such as eating less fat or more ... does not give formal guidelines or recommendations for making decisions about health care. Reviewers and Updates Editorial Boards ...

  7. Microwave Breast Imaging Techniques

    DEFF Research Database (Denmark)

    Zhurbenko, Vitaliy; Rubæk, Tonny

    2010-01-01

    This paper outlines the applicability of microwave radiation for breast cancer detection. Microwave imaging systems are categorized based on their hardware architecture. The advantages and disadvantages of various imaging techniques are discussed. The fundamental tradeoffs are indicated between...

  8. Breast Reconstruction Alternatives

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  9. Breast Reconstruction Options

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  10. Cosmetic breast surgery - discharge

    Science.gov (United States)

    ... Higdon KK. Reduction mammoplasty. In: Neligan PC, ed. Plastic Surgery . 3rd ed. Philadelphia, PA: Elsevier; 2013:chap 8. ... Gabriel A. Breast augmentation. In: Neligan PC, ed. Plastic Surgery . 3rd ed. Philadelphia, PA: Elsevier; 2013:chap 2.

  11. Preeclampsia and breast cancer

    DEFF Research Database (Denmark)

    Pacheco, Nadja Livia Pekkola; Andersen, Anne-Marie Nybo; Kamper-Jørgensen, Mads

    2015-01-01

    BACKGROUND: In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. METHODS: We conducted...... a register-based cohort study of all Danish women giving birth during 1978-2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. RESULTS: Compared...... with women with non-preeclamptic pregnancies only, women with one or more preeclamptic pregnancies were 19% significantly less likely to develop breast cancer (IRR = 0.81 [95% CI 0.72-0.93]). We found some indication of greater risk reduction in women with term births, one or more previous births...

  12. Review and Revelation of Development of Movement of Positive Psychology%积极心理学运动发展的回顾与启示

    Institute of Scientific and Technical Information of China (English)

    李江雪; 魏晓丽; 申荷永

    2012-01-01

    As a influential psychology movement, positive psychology made great progress in the primal 5 years of this century. Through the research into the periodicals and publications of the special issue of positive psychology of American Psychologist (2000) and the special column of positive psychology of Review of General Psychology (2005), this paper reviewed and compared the developmental trend and characteristics of positive psychology, valued the development process of research from human positive quality to human strength, and summarized the revelation of the movement progress of positive psychology.%“积极心理学”作为一种影响广泛的心理学运动,在本世纪初的五年当中获得了重要的研究进展。通过对《美国心理学家》2000年积极心理学专辑和《普通心理学回顾》2005年积极心理学专栏等十余份主要期刊和出版物的研究,文章回顾与比较了积极心理学发展的趋势和特点,评价了其从对“人的积极品质”的研究到“人性积极力量”的研究的发展过程,并总结了关于积极心理学运动发展的启示。

  13. Breast MRI: guidelines from the European Society of Breast Imaging

    International Nuclear Information System (INIS)

    The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity - as in all breast imaging modalities - depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yield MR-only visible questionable lesions that require an MR-guided intervention for clarification, MRI should only be offered by institutions that can also offer a MRI-guided breast biopsy or that are in close contact with a site that can perform this type of biopsy for them. Radiologists involved in breast imaging should ensure that they have a thorough knowledge of the MRI techniques that are necessary for breast imaging, that they know how to evaluate a breast MRI using the ACR BI-RADS MRI lexicon, and most important, when to perform breast MRI. This manuscript provides guidelines on the current best practice for the use of breast MRI, and the methods to be used, from the European Society of Breast Imaging (EUSOBI). (orig.)

  14. Multiplanar breast kinematics during different exercise modalities

    OpenAIRE

    Risius, Debbie; Milligan, Alexandra; Mills, Chris; Scurr, Joanna

    2015-01-01

    Multiplanar breast movement reduction is crucial to increasing physical activity participation amongst women. To date, research has focused on breast movement during running, but until breast movement is understood during different exercise modalities, the breast support requirements for specific activities are unknown. To understand breast support requirements during different exercise modalities, this study aimed to determine multiplanar breast kinematics during running, jumping and agility...

  15. Breast cancer risk factors

    OpenAIRE

    Marzena Kamińska; Tomasz Ciszewski; Karolina Łopacka-Szatan; Paweł Miotła; Elżbieta Starosławska

    2015-01-01

    Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neopla...

  16. Transaxillary Endoscopic Breast Augmentation

    OpenAIRE

    Sim, Hyung-Bo

    2014-01-01

    The axillary technique is the most popular approach to breast augmentation among Korean women. Transaxillary breast augmentation is now conducted with sharp electrocautery dissection under direct endoscopic vision throughout the entire process. The aims of this method are clear: both a bloodless pocket and a sharp non-traumatic dissection. Round textured or anatomical cohesive gel implants have been used to make predictable well-defined inframammary creases because textured surface implants d...

  17. Diet and breast cancer

    OpenAIRE

    Isabelle Romieu

    2011-01-01

    Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability ...

  18. Breast cancer stem cells

    OpenAIRE

    Owens, Thomas W.; Naylor, Matthew J.

    2013-01-01

    Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumors are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs). Understanding how CSCs form and how they contribute to th...

  19. Women and breast cancer.

    OpenAIRE

    Lippman, M E

    1987-01-01

    One in every 12 women will develop breast cancer; the incidence increases with age, dietary fat intake, caloric intake, height, and weight. The 10-year survival rate of breast cancer patients who refuse therapy is virtually zero. Segmental mastectomy plus radiation and lumpectomy, combined with systemic (adjuvant)chemotherapy, are alternatives under investigation at the National Institutes of Health that may increase the survival rate by decreasing metastatic complications.

  20. Targeting Breast Cancer Metastasis

    OpenAIRE

    Xin Jin; Ping Mu

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various me...