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Sample records for breast cancer invasion

  1. Epigenetic suppression of neprilysin regulates breast cancer invasion

    Science.gov (United States)

    Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

    2016-01-01

    In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT–PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer

  2. A microscopic landscape of the invasive breast cancer genome

    OpenAIRE

    Zheng Ping; Yuchao Xia; Tiansheng Shen; Vishwas Parekh; Siegal, Gene P; Isam-Eldin Eltoum; Jianbo He; Dongquan Chen; Minghua Deng; Ruibin Xi; Dejun Shen

    2016-01-01

    Histologic grade is one of the most important microscopic features used to predict the prognosis of invasive breast cancer and may serve as a marker for studying cancer driving genomic abnormalities in vivo. We analyzed whole genome sequencing data from 680 cases of TCGA invasive ductal carcinomas of the breast and correlated them to corresponding pathology information. Ten genetic abnormalities were found to be statistically associated with histologic grade, including three most prevalent ca...

  3. The thioredoxin system in breast cancer cell invasion and migration

    OpenAIRE

    Maneet Bhatia; Kelly L. McGrath; Giovanna Di Trapani; Pornpimol Charoentong; Fenil Shah; Mallory M. King; Clarke, Frank M.; Tonissen, Kathryn F

    2016-01-01

    Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1) in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1) expression with breast cancer patient ...

  4. Biological markers of invasive breast cancer.

    Science.gov (United States)

    Matsumoto, Akiko; Jinno, Hiromitsu; Ando, Tomofumi; Fujii, Taku; Nakamura, Tetsuya; Saito, Junichi; Takahashi, Maiko; Hayashida, Tetsu; Kitagawa, Yuko

    2016-02-01

    Biological markers for breast cancer are biomolecules that result from cancer-related processes and are associated with particular clinical outcomes; they thus help predict responses to therapy. In recent years, gene expression profiling has made the molecular classification of breast cancer possible. Classification of breast cancer by immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67 is standard practice for clinical decision-making. Assessments of hormone receptor expression and human epidermal growth factor receptor 2 overexpression help estimate benefits from targeted therapies and have greatly improved prognoses for women with these breast cancer types. Although Ki-67 positivity is associated with an adverse outcome, its clear identification is an aid to optimal disease management. Standardization of testing methodology to minimize inter-laboratory measurement variations is a remaining issue. Multi-gene assays provide prognostic information and identify those most likely to benefit from systemic chemotherapy. Incorporating molecular profiles with conventional pathological classification would be more precise, and could enhance the clinical development of personalized therapy in breast cancer. PMID:26486826

  5. The thioredoxin system in breast cancer cell invasion and migration

    Directory of Open Access Journals (Sweden)

    Maneet Bhatia

    2016-08-01

    Full Text Available Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1 in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1 expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

  6. The thioredoxin system in breast cancer cell invasion and migration.

    Science.gov (United States)

    Bhatia, Maneet; McGrath, Kelly L; Di Trapani, Giovanna; Charoentong, Pornpimol; Shah, Fenil; King, Mallory M; Clarke, Frank M; Tonissen, Kathryn F

    2016-08-01

    Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1) in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1) expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS) or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS) levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

  7. The thioredoxin system in breast cancer cell invasion and migration.

    Science.gov (United States)

    Bhatia, Maneet; McGrath, Kelly L; Di Trapani, Giovanna; Charoentong, Pornpimol; Shah, Fenil; King, Mallory M; Clarke, Frank M; Tonissen, Kathryn F

    2016-08-01

    Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1) in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1) expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS) or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS) levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration. PMID:26760912

  8. Perspectives of Nanotechnology in Minimally Invasive Therapy of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yamin Yang

    2013-01-01

    Full Text Available Breast cancer, the most common type of cancer among women in the western world, affects approximately one out of every eight women over their lifetime. In recognition of the high invasiveness of surgical excision and severe side effects of chemical and radiation therapies, increasing efforts are made to seek minimally invasive modalities with fewer side effects. Nanoparticles (<100 nm in size have shown promising capabilities for delivering targeted therapeutic drugs to cancer cells and confining the treatment mainly within tumors. Additionally, some nanoparticles exhibit distinct properties, such as conversion of photonic energy into heat, and these properties enable eradication of cancer cells. In this review, current utilization of nanostructures for cancer therapy, especially in minimally invasive therapy, is summarized with a particular interest in breast cancer.

  9. Invasive ductal breast cancer metastatic to the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Zhou Xiao-cong

    2012-11-01

    Full Text Available Abstract The most common sites of breast cancer metastasis are the bone, lung, liver and brain. However, colonic metastases from breast cancer are very rare in the clinic. We describe an unusual case of sigmoid colonic metastasis from invasive ductal breast cancer. With this report, we should increase the clinical awareness that any patient with a colorectal lesion and a history of malignancy should be considered to have a metastasis until proven otherwise. Early diagnosis is very important, which enables prompt initiation of systemic treatment, such as chemotherapy, endocrine therapy or both, thus avoiding unnecessary radical surgical resection and improving the prognosis.

  10. Overweight, Obesity and Postmenopausal Invasive Breast Cancer Risk

    Science.gov (United States)

    Neuhouser, Marian. L; Aragaki, Aaron K.; Prentice, Ross L.; Manson, JoAnn E.; Chlebowski, Rowan; Carty, Cara L.; Ochs-Balcom, Heather M.; Thomson, Cynthia A.; Caan, Bette J.; Tinker, Lesley F.; Urrutia, Rachel Peragallo; Knudtson, Jennifer; Anderson, Garnet L.

    2016-01-01

    IMPORTANCE Over ⅔ of U.S. women are overweight or obese, placing them at increased risk for postmenopausal breast cancer. OBJECTIVE To investigate the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women’s Health Initiative (WHI) Clinical Trial. DESIGN The WHI protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer endpoints. SETTING 40 U.S. clinical centers. PARTICIPANTS n=67,142 postmenopausal women aged 50–79 years were enrolled from 1993–1998 with a median of 13 years of follow-up through 2010; 3388 invasive breast cancers were observed. MAIN OUTCOMES AND MEASURES Height and weight were measured at baseline and weight was measured annually thereafter. Data were collected on demographic characteristics, personal and family medical history and personal habits (smoking, physical activity). Women underwent annual or biennial mammograms. Breast cancers were verified by medical records reviewed by physician adjudicators. RESULTS Women who were overweight and obese had an increased invasive breast cancer risk vs. normal weight women. Risk was greatest for obesity grades 2+3 (BMI>35.0 kg/m2) (hazard ratio [HR] for invasive breast cancer =1.58, 95% CI 1.40–1.79). BMI ≥ 35.0 kg/m2 was strongly associated with risk for ER+/PR+ breast cancers (HR=1.86 95% CI 1.60–2.17), but was not associated with ER− cancers. Obesity grade 2+3 was also associated with advanced disease including larger tumor size (HR=2.12 95%CI 1.67–2.69). (P=0.02), positive lymph nodes (HR=1.89 95%CI 1.46–2.45), (P=0.06), regional/distant stage (HR=1.94, 95%CI 1.52–2.47) (P=0.05) and deaths after breast cancer (HR=2.11 95%CI 1.57–2.84) (P5% of bodyweight over the follow-up period had an increased breast cancer risk (HR=1.36 95% CI 1.1–1.65), but among women already overweight or obese we found no association of weight change (gain or loss

  11. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  12. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    International Nuclear Information System (INIS)

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate

  13. Host epithelial geometry regulates breast cancer cell invasiveness

    Science.gov (United States)

    Boghaert, Eline; Gleghorn, Jason P.; Lee, KangAe; Gjorevski, Nikolce; Radisky, Derek C.; Nelson, Celeste M.

    2012-01-01

    Breast tumor development is regulated in part by cues from the local microenvironment, including interactions with neighboring nontumor cells as well as the ECM. Studies using homogeneous populations of breast cancer cell lines cultured in 3D ECM have shown that increased ECM stiffness stimulates tumor cell invasion. However, at early stages of breast cancer development, malignant cells are surrounded by normal epithelial cells, which have been shown to exert a tumor-suppressive effect on cocultured cancer cells. Here we explored how the biophysical characteristics of the host microenvironment affect the proliferative and invasive tumor phenotype of the earliest stages of tumor development, by using a 3D microfabrication-based approach to engineer ducts composed of normal mammary epithelial cells that contained a single tumor cell. We found that the phenotype of the tumor cell was dictated by its position in the duct: proliferation and invasion were enhanced at the ends and blocked when the tumor cell was located elsewhere within the tissue. Regions of invasion correlated with high endogenous mechanical stress, as shown by finite element modeling and bead displacement experiments, and modulating the contractility of the host epithelium controlled the subsequent invasion of tumor cells. Combining microcomputed tomographic analysis with finite element modeling suggested that predicted regions of high mechanical stress correspond to regions of tumor formation in vivo. This work suggests that the mechanical tone of nontumorigenic host epithelium directs the phenotype of tumor cells and provides additional insight into the instructive role of the mechanical tumor microenvironment. PMID:23150585

  14. Technetium-99m sestamibi: an indicator of breast cancer invasiveness

    International Nuclear Information System (INIS)

    As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with 99mTc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revesion showed a positive 99mTc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm2 and one showed 99 microvessels/mm2; by contrast there were 71.6±12.1 microvessels/mm2 in the nine N- and sestamibi-negative tumours. Our study suggests that 99mTc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour. (orig.)

  15. Technetium-99m sestamibi: an indicator of breast cancer invasiveness

    Energy Technology Data Exchange (ETDEWEB)

    Scopinaro, F. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Schillaci, O. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Scarpini, M. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Mingazzini, P.L. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Di Macio, L. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Banci, M. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Danieli, R. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Zerilli, M. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Limiti, M.R. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Centi Colella, A. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy))

    1994-09-01

    As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with [sup 99m]Tc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revesion showed a positive [sup 99m]Tc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm[sup 2] and one showed 99 microvessels/mm[sup 2]; by contrast there were 71.6[+-]12.1 microvessels/mm[sup 2] in the nine N- and sestamibi-negative tumours. Our study suggests that [sup 99m]Tc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour. (orig.)

  16. Parameter estimates for invasive breast cancer progression in the Canadian National Breast Screening Study

    OpenAIRE

    Taghipour, S.; Banjevic, D; Miller, A.B.; Montgomery, N; A K S Jardine; Harvey, B. J.

    2013-01-01

    Background: The aim of screening is to detect a cancer in the preclinical state. However, a false-positive or a false-negative test result is a real possibility. Methods: We describe invasive breast cancer progression in the Canadian National Breast Screening Study and construct progression models with and without covariates. The effect of risk factors on transition intensities and false-negative probability is investigated. We estimate the transition rates, the sojourn time and sensitivity o...

  17. The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy

    OpenAIRE

    Liu, Ying; Cao, Wei; Zhang, Bo; Liu, Yong-Qiang; Wang, Zhong-yuan; Wu, Yan-ping; Yu, Xian-jun; Zhang, Xu-Dong; Ming, Ping-hong; Zhou, Guang-Biao; Huang, Laiqiang

    2013-01-01

    Invasion and metastasis are the main causes of treatment failure and death in breast cancer. Thus, novel invasion-based therapies such as those involving natural agents are urgently required. In this study, we examined the effects of magnolol (Mag), a compound extracted from medicinal herbs, on breast cancer cells in vitro and in vivo. Highly invasive cancer cells were found to be highly sensitive to treatment. Mag markedly inhibited the activity of highly invasive MDA-MB-231 cells. Furthermo...

  18. Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.

    Science.gov (United States)

    Onoe, Shunsuke; Tsuda, Hitoshi; Akashi-Tanaka, Sadako; Hasebe, Takahiro; Iwamoto, Eriko; Hojo, Takashi; Kinoshita, Takayuki

    2014-03-01

    We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed. PMID:21140247

  19. Cancer-Associated Adipocytes Exhibit an ActivatedPhenotype and Contribute to Breast Cancer Invasion

    OpenAIRE

    2011-01-01

    Early local tumor invasion in breast cancer results in a likely encounter between cancer cells and matureadipocytes, but the role of these fat cells in tumor progression remains unclear. We show that murine and humantumor cells cocultivated with mature adipocytes exhibit increased invasive capacities in vitro and in vivo, usingan original two-dimensional coculture system. Likewise, adipocytes cultivated with cancer cells also exhibit analtered phenotype in terms of delipidation and decreased ...

  20. Managing the risk of invasive breast cancer in women at risk for breast cancer and osteoporosis: the role of raloxifene

    Directory of Open Access Journals (Sweden)

    Victor G Vogel

    2008-12-01

    Full Text Available Victor G VogelThe University of Pittsburgh Cancer Institute, Magee-Womens Hospital, Pittsburgh, PA, USAAbstract: Raloxifene hydrochloride is a selective estrogen receptor modulator (SERM that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. Raloxifene significantly improves serum lipids and serum markers of cardiovascular disease risk, but it has no significant effect on the risk of primary coronary events. A meta-analysis of randomized, double-blind, placebo-controlled trials of raloxifene for osteoporosis showed the odds of fracture risk were 0.60 (95% confidence interval [CI] = 0.49–0.74 for raloxifene 60 mg/day compared with placebo. During 8 years of follow-up in an osteoporosis trial, the raloxifene group had a 76% reduction in the incidence of invasive ER-positive breast cancer compared with the placebo group. In the STAR trial, the incidence of invasive breast cancer was 4.30 per 1000 women-years with raloxifene and 4.41 per 1000 with tamoxifen; RR = 1.02; 95% CI, 0.82–1.28. The effect of raloxifene on invasive breast cancer was, therefore, equivalent to that of tamoxifen with more favorable rates of adverse effects including uterine malignancy and clotting events. Millions of postmenopausal women could derive net benefit from raloxifene through reduced rates of fracture and invasive breast cancer.Keywords: raloxifene, osteoporosis, breast cancer risk reduction

  1. Delayed breast reconstruction with implants after invasive breast cancer does not impair prognosis

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Düring, Maria; Henriksen, Trine Foged;

    2008-01-01

    We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women......We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women...

  2. FGFR1 amplification and the progression of non-invasive to invasive breast cancer

    OpenAIRE

    Gru, Alejandro A.; Allred, D. Craig

    2012-01-01

    The incidence of invasive breast cancer (IBC) can be dramatically reduced by improving our abilities to detect and treat ductal carcinoma in situ (DCIS). Progress will be based on a detailed understanding of molecular mechanisms responsible for tumor progression. An interesting study by Jang and colleagues evaluated and compared the frequency of amplification of four oncogenes (HER2, c-MYC, CCND1 and FGFR1) in large cohorts of pure DCIS, in the DCIS component of IBC, and in corresponding IBC....

  3. Effects of osthole on migration and invasion in breast cancer cells.

    Science.gov (United States)

    Yang, Dapeng; Gu, Tianwei; Wang, Ting; Tang, Qingjiu; Ma, Changyan

    2010-01-01

    Osthole, a natural coumarin derivative, is extracted from the fruit of Cnidium monnieri Cusson. Breast cancer is one of the most commonly diagnosed cancers and the leading cause of death in women. Recent studies have shown that Osthole has anti-tumor activity. However, the effects of Osthole on the migration and invasion of cancer cells have not yet been reported. Here, we found that Osthole is effective in inhibiting the migration and invasion of breast cancer cells by wound healing and transwell assays. Luciferase and zymography assays revealed that Osthole effectively inhibits matrix metalloproteinase-2 promoter and enzyme activity, which might be one of the causes that lead to the inhibition of migration and invasion by Osthole. This is the first report on the inhibitory function of Osthole in migration and invasion in breast cancer cells. Our findings indicate a need for further evaluation of Osthole in breast cancer chemotherapy and chemoprevention. PMID:20622464

  4. Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer

    Institute of Scientific and Technical Information of China (English)

    Lukui Yang; Long Li; Xiangyu Cui; Dalei Yang

    2015-01-01

    Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor (VEGF) and CD105-microvessel density (MVD) in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods Immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expres-sion. Positively stained microvessels were counted in dense vascular foci under 400× magnification. MVD in the peripheral area adjacent to the lesion and in the central area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue (22.0%, P 0.05). MVD of the peripheral area adja-cent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benign breast disease groups (P 50 years) or the two tumor diameter groups (≤2 cm vs.>2 cm), P > 0.05. Conclusion Overexpression of VEGF and MVD may be important biological markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor mark-ers could provide better prognostic monitoring for disease recurrence and metastasis, as wel as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as wel as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better fol ow-up regimens and appro-priate treatment strategies for breast cancer patients.

  5. c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion.

    Science.gov (United States)

    Wang, Liyang; Hou, Yixuan; Sun, Yan; Zhao, Liuyang; Tang, Xi; Hu, Ping; Yang, Jiajia; Zeng, Zongyue; Yang, Guanglun; Cui, Xiaojiang; Liu, Manran

    2013-12-01

    Aberrant expression of c-Ski oncoprotein in some tumor cells has been shown to be associated with cancer development. However, the role of c-Ski in cancer-associated fibroblasts (CAFs) of tumor microenvironment has not been characterized. In the current study, we found that c-Ski is highly expressed in CAFs derived from breast carcinoma microenvironment and this CAF-associated c-Ski expression is associated with invasion and metastasis of human breast tumors. We showed that c-Ski overexpression in immortalized breast normal fibroblasts (NFs) induces conversion to breast CAFs by repressing p53 and thereby upregulating SDF-1 in NFs. SDF-1 treatment or p53 knockdown in NFs had similar effects on the activation of NFs as c-Ski overexpression. The c-Ski-activated CAFs show increased proliferation, migration, invasion and contraction compared with NFs. Furthermore, c-Ski-activated CAFs facilitated the migration and invasion of MDA-MB-231 breast cancer cells. Our data suggest that c-Ski is an important regulator in the activation of CAFs and may serve as a potential therapeutic target to block breast cancer progression.

  6. DEGRO practical guidelines for radiotherapy of breast cancer IV. Radiotherapy following mastectomy for invasive breast cancer

    International Nuclear Information System (INIS)

    Since the last recommendations from the Breast Cancer Expert Panel of the German Society for Radiation Oncology (DEGRO) in 2008, evidence for the effectiveness of postmastectomy radiotherapy (PMRT) has grown. This growth is based on updates of the national S3 and international guidelines, as well as on new data and meta-analyses. New aspects were considered when updating the DEGRO recommendations. The authors performed a comprehensive survey of the literature. Data from recently published (meta-)analyses, randomized clinical trials and international cancer societies' guidelines yielding new aspects compared to 2008 were reviewed and discussed. New aspects were included in the current guidelines. Specific issues relating to particular PMRT constellations, such as the presence of risk factors (lymphovascular invasion, blood vessel invasion, positive lymph node ratio > 20 %, resection margins 2 cm or a combination of ≥ 2 risk factors) and 1-3 positive lymph nodes are emphasized. The evidence for improved overall survival and local control following PMRT for T4 tumors, positive resection margins, > 3 positive lymph nodes and in T3 N0 patients with risk factors such as lymphovascular invasion, G3 grading, close margins, and young age has increased. Recently identified risk factors such as invasive lobular subtype and negative hormone receptor status were included. For patients with 1-3 positive lymph nodes, the recommendation for PMRT has reached the 1a level of evidence. PMRT is mandatory in patients with T4 tumors and/or positive lymph nodes and/or positive resection margins. PMRT should be strongly considered in patients with T3 N0 tumors and risk factors, particularly when two or more risk factors are present. (orig.)

  7. DEGRO practical guidelines for radiotherapy of breast cancer IV. Radiotherapy following mastectomy for invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wenz, Frederik; Sperk, Elena [Universitaetsmedizin Mannheim, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany); Budach, Wilfried [Heinrich-Heine-University, Duesseldorf (Germany); Dunst, Juergen [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, Petra [Vivantes Hospital Neukoelln, Berlin (Germany); Fietkau, Rainer; Sauer, Rolf [University Hospital Erlangen, Erlangen (Germany); Haase, Wulf [Formerly St.-Vincentius-Hospital, Karlsruhe (Germany); Harms, Wolfgang [St. Clara Hospital, Basel (Switzerland); Piroth, Marc D. [Helios Hospital, Wuppertal (Germany); Sautter-Bihl, Marie-Luise [Municipal Hospital, Karlsruhe (Germany); Sedlmayer, Felix; Fussl, Christoph [Paracelsus Medical University Hospital, Salzburg (Germany); Souchon, Rainer; Collaboration: Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

    2014-08-15

    Since the last recommendations from the Breast Cancer Expert Panel of the German Society for Radiation Oncology (DEGRO) in 2008, evidence for the effectiveness of postmastectomy radiotherapy (PMRT) has grown. This growth is based on updates of the national S3 and international guidelines, as well as on new data and meta-analyses. New aspects were considered when updating the DEGRO recommendations. The authors performed a comprehensive survey of the literature. Data from recently published (meta-)analyses, randomized clinical trials and international cancer societies' guidelines yielding new aspects compared to 2008 were reviewed and discussed. New aspects were included in the current guidelines. Specific issues relating to particular PMRT constellations, such as the presence of risk factors (lymphovascular invasion, blood vessel invasion, positive lymph node ratio > 20 %, resection margins < 3 mm, G3 grading, young age/premenopausal status, extracapsular invasion, negative hormone receptor status, invasive lobular cancer, size > 2 cm or a combination of ≥ 2 risk factors) and 1-3 positive lymph nodes are emphasized. The evidence for improved overall survival and local control following PMRT for T4 tumors, positive resection margins, > 3 positive lymph nodes and in T3 N0 patients with risk factors such as lymphovascular invasion, G3 grading, close margins, and young age has increased. Recently identified risk factors such as invasive lobular subtype and negative hormone receptor status were included. For patients with 1-3 positive lymph nodes, the recommendation for PMRT has reached the 1a level of evidence. PMRT is mandatory in patients with T4 tumors and/or positive lymph nodes and/or positive resection margins. PMRT should be strongly considered in patients with T3 N0 tumors and risk factors, particularly when two or more risk factors are present. (orig.) [German] Seit der letzten Aktualisierung der 2008 publizierten Leitlinie der &apos

  8. Differential expression of matrix metalloproteinase-13 in association with invasion of breast cancer.

    Science.gov (United States)

    Kotepui, Manas; Punsawad, Chuchard; Chupeerach, Chaowanee; Songsri, Apiram; Charoenkijkajorn, Lek; Petmitr, Songsak

    2016-01-01

    Matrix metalloproteinase-13 (MMP-13) has a potential role in tumour invasion and metastasis. However, its relevance to the prognosis of human breast cancer is poorly understood. The aim of this study is to investigate the expression patterns of MMP-13 protein and to determine its prognostic value in breast cancer, and to define its relation to the clinicopathological features. Immunohistochemistry analysis of MMP-13 was performed on formalin-fixed, paraffin-embedded sections of cancerous breast tissue (n = 76) and normal breast tissue (n = 20), all of which had clinicopathological information available. Based on the principle of immunoreactivity, the detection of MMP-13 on breast tissue was conducted using monoclonal antibodies against MMP-13. A semi-quantitative scoring system was used to assess the presence of, as well as the cellular localisation of MMP-13. MMP-13 expression was significantly greater in the cancerous breast tissues in comparison to those of normal breast tissues. In addition, high levels of MMP-13 expression were also found to be related to the positive detection of breast cancer cells in lymph nodes-amongst breast cancer patients. The results of this study showed that MMP-13 was frequently present in breast tumours, especially when tumours were accompanied by positive breast cancer cell detection in lymph nodes. This suggests that MMP-13 plays a potentially significant role in breast cancer invasion and metastasis. PMID:27647987

  9. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

    Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

  10. Mitosis Detection for Invasive Breast Cancer Grading in Histopathological Images.

    Science.gov (United States)

    Paul, Angshuman; Mukherjee, Dipti Prasad

    2015-11-01

    Histopathological grading of cancer not only offers an insight to the patients' prognosis but also helps in making individual treatment plans. Mitosis counts in histopathological slides play a crucial role for invasive breast cancer grading using the Nottingham grading system. Pathologists perform this grading by manual examinations of a few thousand images for each patient. Hence, finding the mitotic figures from these images is a tedious job and also prone to observer variability due to variations in the appearances of the mitotic cells. We propose a fast and accurate approach for automatic mitosis detection from histopathological images. We employ area morphological scale space for cell segmentation. The scale space is constructed in a novel manner by restricting the scales with the maximization of relative-entropy between the cells and the background. This results in precise cell segmentation. The segmented cells are classified in mitotic and non-mitotic category using the random forest classifier. Experiments show at least 12% improvement in F1 score on more than 450 histopathological images at 40× magnification.

  11. 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.

  12. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    ABSTRACT: BACKGROUND: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers m

  13. Astrocyte elevated gene-1 induces breast cancer proliferation and invasion through upregulating HER2/neu expression

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin; ZHANG Ning; ZHANG Mei-xin

    2011-01-01

    Background Astrocyte elevated gene-1 (AEG-1),primarily identified as a late response gene induced by HIV-1 infection,plays multiple roles in the process of oncogenesis.This novel gene has been demonstrated to be involved in the several potent carcinogenic pathways,including PI3K/Akt pathway,nuclear factor (NF)-KB pathway,and Wnt/β-catenin pathway.Although the function of AEG-1 has been intensively investigated in recent years,the molecular mechanism underlying its oncogenic role is largely unknown.The aim of this research was to explore the potential function of AEG-1 in breast cancer development and progression.Methods AEG-1 was ectopically overexpressed in breast cancer MCF-7 cells and its biological effects on the proliferation and invasion of MCF-7 cells were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and invasion assays.The expression of HER2/neu,a crucial oncogene involving in breast cancer carcinogenesis,was also determined.Results Overexpression of the AEG-1 promoted the proliferation and invasion ability of breast cancer cells,and upregulated the expression of HER2/neu,a crucial oncogene involving in breast cancer carcinogenesis.Conclusion AEG-1 might facilitate the proliferation and invasion of breast cancer cells by upregulating HER2/neu expression,which provides a potential target for breast cancer therapy.

  14. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

    2009-06-18

    Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also

  15. Upregulation of HYAL1 expression in breast cancer promoted tumor cell proliferation, migration, invasion and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Jin-Xiang Tan

    Full Text Available Hyaluronic acid (HA is a component of the Extra-cellular matrix (ECM, it is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronidase (HAase is a HA-degrading endoglycosidase, levels of HAase are elevated in many cancers. Hyaluronidase-1 (HYAL1 is the major tumor-derived HAase. We previously demonstrated that HYAL1 were overexpression in human breast cancer. Breast cancer cells with higher HAase expression, exhibited significantly higher invasion ability through matrigel than those cells with lower HAase expression, and knockdown of HYAL1 expression in breast cancer cells resulted in decreased cell growth, adhesion, invasion and angiogenesis. Here, to further elucidate the function of HYAL1 in breast cancer, we investigated the consequences of forcing HYAL1 expression in breast cancer cells by transfection of expression plasmid. Compared with control, HYAL1 up-regulated cells showed increased the HAase activity, and reduced the expression of HA in vitro. Meantime, upregulation of HYAL1 promoted the cell growth, migration, invasion and angiogenesis in vitro. Moreover, in nude mice model, forcing HYAL1 expression induced breast cancer cell xenograft tumor growth and angiogenesis. Interestingly, the HA expression was upregulated by forcing HYAL1 expression in vivo. These findings suggested that HYAL1-HA system is correlated with the malignant behavior of breast cancer.

  16. Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer

    Science.gov (United States)

    Zelinski, Teresa; Xie, Jiuyong; Cooper, Steven; Penner, Carla; Leygue, Etienne; Myal, Yvonne

    2016-01-01

    Background The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mechanism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have been identified to date in breast cancer. Since many genes have been shown to undergo deregulation through splicing and mis-splicing events in cancer, the current study was undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive breast cancer. Methods RT-PCR analysis of CLDN1 transcripts was conducted on RNA isolated from 12 human invasive breast tumors. The PCR products from each tumor were resolved by agarose gel electrophoresis, cloned and sequenced. Genomic DNA was also isolated from each of the 12 tumors and amplified using PCR CLDN1 specific primers. Sanger sequencing and single nucleotide polymorphism (SNP) analyses were conducted. Results A number of CLDN1 transcript variants were identified in these breast tumors. All variants were shorter than the classical CLDN1 transcript. Sequence analysis of the PCR products revealed several splice variants, primarily in exon 1 of CLDN1; resulting in truncated proteins. One variant, V1, resulted in a premature stop codon and thus likely led to nonsense mediated decay. Interestingly, another transcript variant, V2, was not detected in normal breast tissue samples. Further, sequence analysis of the tumor genomic DNA revealed SNPs in 3 of the 4 coding exons, including a rare missense SNP (rs140846629) in exon 2 which represents an Ala124Thr substitution. To our knowledge this is the first report of CLDN1 transcript variants in human invasive breast cancer. These studies suggest that alternate splicing may also be a mechanism by which claudin 1 is down regulated at both the mRNA and protein levels in invasive breast cancer and may provide novel insights into how CLDN1 is reduced or silenced in human breast

  17. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Cekanova, Maria, E-mail: mcekanov@utk.edu [Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Fernando, Romaine I. [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Siriwardhana, Nalin [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Sukhthankar, Mugdha [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Parra, Columba de la [Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR (United States); Woraratphoka, Jirayus [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Malone, Christine [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Ström, Anders [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Baek, Seung J. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Wade, Paul A. [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Saxton, Arnold M. [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Donnell, Robert M. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Pestell, Richard G. [Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); and others

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis.

  18. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    International Nuclear Information System (INIS)

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis

  19. TGF-beta and BMP in breast cancer cell invasion

    NARCIS (Netherlands)

    Naber, Hildegonda Petronella Henriëtte

    2012-01-01

    TGF-beta and BMPs are members of the TGF-beta superfamily of cytokines which play an important role in a multitude of processes. In cancer, TGF-beta is known for its dual role: in early stages it inhibits cancer cell proliferation, whereas in later stages it promotes invasion and metastasis. In this

  20. Metadherin mediates lipopolysaccharide-induced migration and invasion of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Yuhan Zhao

    Full Text Available BACKGROUND: Breast cancer is the most prevalent cancer in women worldwide and metastatic breast cancer has very poor prognosis. Inflammation has been implicated in migration and metastasis of breast cancer, although the exact molecular mechanism remains elusive. PRINCIPAL FINDINGS: We show that the pro-inflammatory endotoxin Lipopolysaccharide (LPS upregulates the expression of Metadherin (MTDH, a recently identified oncogene, in a number of breast cancer lines. Stable knockdown of MTDH by shRNA in human breast MDA-MB-231 cells abolishes LPS-induced cell migration and invasion as determined by several in vitro assays. In addition, knockdown of MTDH diminishes Nuclear Factor-kappa B (NF-κB activation by LPS and inhibited LPS-induced IL-8 and MMP-9 production. CONCLUSIONS: These results strongly suggest that MTDH is a pivotal molecule in inflammation-mediated tumor metastasis. Since NF-κB, IL-8 and MMP-9 play roles in LPS-induced invasion or metastasis, the mechanism of MTDH-promoted invasion and metastasis may be through the activation of NF-κB, IL-8 and MMP-9, also suggesting a role of MTDH in regulating both inflammatory responses and inflammation-associated tumor invasion. These findings indicate that MTDH is involved in inflammation-induced tumor progression, and support that MTDH targeting therapy may hold promising prospects in treating breast cancer.

  1. Life expectancy of screen-detected invasive breast cancer patients compared with women invited to the Nijmegen Screening Program

    NARCIS (Netherlands)

    J.D.M. Otten; M.J.M. Broeders (Mireille); G.J. den Heeten (Gerard); R. Holland (Roland); J. Fracheboud (Jacques); H.J. de Koning (Harry); A.L.M. Verbeek (Andre)

    2010-01-01

    textabstractBACKGROUND: Screening can lead to earlier detection of breast cancer and thus to an improvement in survival. The authors studied the life expectancy of women with screen-detected invasive breast cancer (patients) compared with women invited to the breast cancer screening program in Nijme

  2. Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2.

    Directory of Open Access Journals (Sweden)

    Chen Wang

    Full Text Available A better understanding of the effects of human adipocytes on breast cancer cells may lead to the development of new treatment strategies. We explored the effects of adipocytes on the migration and invasion of breast cancer cells both in vitro and in vivo.To study the reciprocal effects of adipocytes and cancer cells, we co-cultured human mature adipocytes and breast cancer cells in a system devoid of heterogeneous cell-cell contact. To analyze the factors that were secreted from adipocytes and that affected the invasive abilities of breast cancer cells, we detected different cytokines in various co-culture media. To study the communication of mature adipocytes and breast cancer cells in vivo, we chose 10 metastatic pathologic samples and 10 non-metastatic pathologic samples to do immunostaining.The co-culture media of human MCF-7 breast cancer cells and human mature adipocytes increased motility of MCF-7 cells. In addition, MMP-2 was remarkably up-regulated, whereas E-cadherin was down-regulated in these MCF-7 cells. Based on our co-culture medium chip results, we chose four candidate cytokines and tested their influence on metastasis individually. We found that IGFBP-2 enhanced the invasion ability of MCF-7 cells in vitro more prominently than did the other factors. In vivo, metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue, whereas adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did adipocytes surrounding non-metastatic breast tumors.IGFBP-2 secreted by mature adipocytes plays a key role in promoting the metastatic ability of MCF-7 breast cancer cells.

  3. miR-708/LSD1 axis regulates the proliferation and invasion of breast cancer cells.

    Science.gov (United States)

    Ma, Lin; Ma, Shan; Zhao, Guimei; Yang, Longqiu; Zhang, Peng; Yi, Qingting; Cheng, Shuguang

    2016-04-01

    Breast cancer is one of the most common malignant tumors in women worldwide. The microRNAs (miRNAs) are small, noncoding RNAs that regulate various biological processes, including breast cancer. miR-708 played an important role in a variety of cancers. However, its involvement in breast cancer remains largely unclear. In this study, we found that forced the expression of miR-708 in breast cancer cell lines decreased cell proliferation and invasion, whereas inhibition of miR-708 increased cell growth and invasion. miR-708 could directly target the LSD1 3'UTR to downregulate the expression. Further studies suggested that inhibition of LSD1 could phenocopied function of the miR-708 overexpression in MDA-MB-231 cells .Overexpression of LSD1 could counteract the effects of miR-708 on the proliferation and invasion. Taken together, the results indicate that miR-708 may function as a tumor suppressor gene in breast cancer development, and miR-708/LSD1 axis may be a therapeutic intervention in breast cancer in the future. PMID:26833707

  4. miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10

    International Nuclear Information System (INIS)

    miRNAs are a group of small RNA molecules regulating target genes by inducing mRNA degradation or translational repression. Aberrant expression of miRNAs correlates with various cancers. Although miR-135a has been implicated in several other cancers, its role in breast cancer is unknown. HOXA10 however, is associated with multiple cancer types and was recently shown to induce p53 expression in breast cancer cells and reduce their invasive ability. Because HOXA10 is a confirmed miR-135a target in more than one tissue, we examined miR-135a levels in relation to breast cancer phenotypes to determine if miR-135a plays role in this cancer type. Expression levels of miR-135a in tissues and cells were determined by poly (A)-RT PCR. The effect of miR-135a on proliferation was evaluated by CCK8 assay, cell migration and invasion were evaluated by transwell migration and invasion assays, and target protein expression was determined by western blotting. GFP and luciferase reporter plasmids were constructed to confirm the action of miR-135a on downstream target genes including HOXA10. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student's t-test. Here we report that miR-135a was highly expressed in metastatic breast tumors. We found that the expression of miR-135a was required for the migration and invasion of breast cancer cells, but not their proliferation. HOXA10, which encodes a transcription factor required for embryonic development and is a metastasis suppressor in breast cancer, was shown to be a direct target of miR-135a in breast cancer cells. Our analysis showed that miR-135a suppressed the expression of HOXA10 both at the mRNA and protein level, and its ability to promote cellular migration and invasion was partially reversed by overexpression of HOXA10. In summary, our results indicate that miR-135a is an onco-miRNA that can promote breast cancer cell migration and invasion. HOXA10 is a target gene for mi

  5. The mammographic correlations of a new immunohistochemical classification of invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taneja, S. [Nottingham Breast Institute, City Hospital, Hucknall Road, Nottingham NG5 1PB (United Kingdom)], E-mail: sheeba_taneja@yahoo.co.uk; Evans, A.J. [Nottingham Breast Institute, City Hospital, Hucknall Road, Nottingham NG5 1PB (United Kingdom); Rakha, E.A.; Green, A.R. [Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham (United Kingdom); Ball, G. [Nottingham Trent University, School of Biomedical and Natural Sciences, Nottingham (United Kingdom); Ellis, I.O. [Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham (United Kingdom)

    2008-11-15

    Aim: Recent protein expression profiling of breast cancer has identified specific subtypes with clinical, biological, and therapeutic implications. The aim of this study was to identify the mammographic correlates of these novel molecular classes of invasive breast cancer. Materials and methods: The mammographic findings of 415 patients with operable breast cancer were correlated with the previously described protein expression classes identified by our group using immunohistochemical (IHC) assessment of a large series of breast cancer cases prepared as tissue microarrays (TMAs). Twenty-five proteins of known relevance in breast cancer were assessed, including hormone receptors, HER-2 status, basal and luminal markers, p53 expression, and E-cadherin. Results: The mammographic background pattern and proportion of lesions that were mammographically occult were similar in all groups. Groups characterized by luminal and hormone receptor positivity had significantly more spiculate lesions at mammography. Groups characterized by HER-2 overexpression, basal characteristics, and E-cadherin positivity had a significantly higher proportion of ill-defined masses. These findings were independent of histological grade. Conclusion: The mammographic features of breast cancer show significant correlation with molecular classes of invasive breast cancer identified by protein expression IHC analysis. The biological reasons for the findings and implications of these regarding imaging protocols require further study and may provide mechanisms for improvement of detection of these lesions.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-08

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

  7. [Advances of the Role of Ezrin in Migration and Invasion of Breast Cancer Cells].

    Science.gov (United States)

    Long, Zhi-Yuan; Wang, Ting-Huai

    2016-02-01

    Ezrin, also known as cytovillin or vilin 2, is one of the members of ERM (Ezrin/Radixin/Moesin) protein family. Ezrin, which is a tyrosine kinase substrate, functions to bridge membrane proteins and the actin cytoskeleton. Recent studies have demonstrated that Ezrin regulates the proliferation, apoptosis, adhesion, invasion, metastasis and angiogenesis of breast cancer cells. These processes are not only associated with changes in expression level and subcellular localization of Ezrin itself, but also influenced by alteration in microenvironment of primary breast cancer cells. The regulation of Ezrin in mammary carcinoma cells involves interactions among signaling pathways mediated by adhesion molecules (CD44, ICAM, E-cadherin) and the tyrosine kinase growth factors, Epidermal Growth Factor (EGF), and Platelet-derived Growth Factor (PDGF) and their receptors. The determination of the functions and mechanism(s) of action of Ezrin in the migration and invasion of breast cancer cells will provide new information on the basic mechanisms of metastasis of breast cancer cells and has the potential to identify a novel drug target for the prevention and treatment of breast cancer. This article addresses the role of Ezrin in the migration and invasion of breast cancer cells. PMID:27424401

  8. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.;

    2008-01-01

    Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...... cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; P(trend) = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor...

  9. SREBP-1 is an independent prognostic marker and promotes invasion and migration in breast cancer

    Science.gov (United States)

    Bao, Jisheng; Zhu, Liping; Zhu, Qi; Su, Jianhua; Liu, Menglan; Huang, Wei

    2016-01-01

    Re-programming of lipogenic signaling has been previously demonstrated to result in significant alterations in tumor cell pathology. Sterol regulatory element-binding protein 1 (SREBP-1) is a known transcription factor of lipogenic genes. Despite the fact that its functions in proliferation and apoptosis have been elucidated in recent studies, its role in tumor cell migration and invasion, particularly in breast cancer, remains unclear. In present study, the messenger RNA and protein expression levels of SREBP-1 in cancer tissues were observed to be overexpressed compared with those in matched para-cancerous tissues (Pmigration and invasion (Pmigration and invasion, and may serve as a prognostic marker of this malignancy.

  10. Update on raloxifene: role in reducing the risk of invasive breast cancer in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Vogel VG

    2011-10-01

    Full Text Available Victor G Vogel Cancer Institute, Geisinger Health System, Danville, PA, USA Abstract: Risk factors allow us to define women who are at increased lifetime risk for breast cancer, and the most important factor is age. Benign breast disease increases risk, and the most important histologies are atypical lobular or ductal hyperplasia and lobular carcinoma in situ. Family history of breast cancer among first-degree relatives (mother, sisters, daughters also increases risk. Quantitative measures of risk give accurate predictions of breast cancer incidence for groups of women but not for individual subjects. Multiple published, randomized controlled trials, which employed selective estrogen receptor (ER modulators (SERMs, have demonstrated consistent reductions of 35% or greater in the risk of ER-positive invasive and noninvasive breast cancer in postmenopausal women. Professional organizations in the US now recommend the use of SERMs to reduce the risk of breast cancer in high-risk, postmenopausal women. Raloxifene and tamoxifen reduce the risk of ER-positive invasive breast cancer with equal efficacy, but raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in breast cancer risk from either agent translates into reduced breast cancer mortality. Overall quality of life is similar with raloxifene or tamoxifen, but the incidence of dyspareunia, weight gain, and musculoskeletal complaints is higher with raloxifene use, whereas vasomotor symptoms, bladder incontinence, gynecologic symptoms, and leg cramps were higher with tamoxifen use. Keywords: selective estrogen receptor modulators (SERMs, raloxifene, risk reduction, chemoprevention

  11. DDRs: receptors that mediate adhesion, migration and invasion in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Emmanuel Reyes-Uribe

    2015-08-01

    Full Text Available Discoidin domain receptors (DDRs are receptor tyrosine kinases that are activated by native collagens and have an important role during cell adhesion, development, differentiation, proliferation, and migration. DDR deregulation is associated with progression of several different cancers. However, there is limited information about the role of DDRs in the progression of breast cancer. In this review we attempt to collect the most relevant information about DDR signaling and their role in various cancer-related processes such as adhesion, epithelial to mesenchymal transition, migration, invasion, and survival, with a focus on breast cancer.

  12. 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

  13. Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls

    Directory of Open Access Journals (Sweden)

    van der Wall Elsken

    2010-04-01

    Full Text Available Abstract Background Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like type that is known to have a low rate of lympho-vascular invasion (LVI, we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. Methods A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. Results LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78. Conclusion LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation.

  14. BLT2 up-regulates interleukin-8 production and promotes the invasiveness of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Hyunju Kim

    Full Text Available BACKGROUND: The elevated production of interleukin (IL-8 is critically associated with invasiveness and metastatic potential in breast cancer cells. However, the intracellular signaling pathway responsible for up-regulation of IL-8 production in breast cancer cells has remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we report that the expression of BLT2 is markedly up-regulated in the highly aggressive human breast cancer cell lines MDA-MB-231 and MDA-MB-435 compared with MCF-10A immortalized human mammary epithelial cells, as determined by RT-PCR, real-time PCR and FACS analysis. Blockade of BLT2 with BLT2 siRNA knockdown or BLT2 inhibitor treatment downregulated IL-8 production and thereby diminished the invasiveness of aggressive breast cancer cells, analyzed by Matrigel invasion chamber assays. We further characterized the downstream signaling mechanism by which BLT2 stimulates IL-8 production and identified critical mediatory roles for the generation of reactive oxygen species (ROS and the consequent activation of the transcription factor NF-κB. Moreover, blockade of BLT2 suppressed the formation of metastatic lung nodules by MDA-MB-231 cells in both experimental and orthotopic metastasis models. CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrates that a BLT2-ROS-NF-κB pathway up-regulates IL-8 production in MDA-MB-231 and MDA-MB-435 cells, thereby contributing to the invasiveness of these aggressive breast cancer cells. Our findings provide insight into the molecular mechanism of invasiveness in breast cancer.

  15. Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancers.

    Science.gov (United States)

    Wang, Zhigang C; Lin, Ming; Wei, Lee-Jen; Li, Cheng; Miron, Alexander; Lodeiro, Gabriella; Harris, Lyndsay; Ramaswamy, Sridhar; Tanenbaum, David M; Meyerson, Matthew; Iglehart, James D; Richardson, Andrea

    2004-01-01

    Gene expression array profiles identify subclasses of breast cancers with different clinical outcomes and different molecular features. The present study attempted to correlate genomic alterations (loss of heterozygosity; LOH) with subclasses of breast cancers having distinct gene expression signatures. Hierarchical clustering of expression array data from 89 invasive breast cancers identified four major expression subclasses. Thirty-four of these cases representative of the four subclasses were microdissected and allelotyped using genome-wide single nucleotide polymorphism detection arrays (Affymetrix, Inc.). LOH was determined by comparing tumor and normal single nucleotide polymorphism allelotypes. A newly developed statistical tool was used to determine the chromosomal regions of frequent LOH. We found that breast cancers were highly heterogeneous, with the proportion of LOH ranging widely from 0.3% to >60% of heterozygous markers. The most common sites of LOH were on 17p, 17q, 16q, 11q, and 14q, sites reported in previous LOH studies. Signature LOH events were discovered in certain expression subclasses. Unique regions of LOH on 5q and 4p marked a subclass of breast cancers with "basal-like" expression profiles, distinct from other subclasses. LOH on 1p and 16q occurred preferentially in a subclass of estrogen receptor-positive breast cancers. Finding unique LOH patterns in different groups of breast cancer, in part defined by expression signatures, adds confidence to newer schemes of molecular classification. Furthermore, exclusive association between biological subclasses and restricted LOH events provides rationale to search for targeted genes.

  16. MEK-dependent IL-8 induction regulates the invasiveness of triple-negative breast cancer cells.

    Science.gov (United States)

    Kim, Sangmin; Lee, Jeongmin; Jeon, Myeongjin; Lee, Jeong Eon; Nam, Seok Jin

    2016-04-01

    Interleukin-8 (IL-8) serves as a prognostic marker for breast cancer, and its expression level correlates with metastatic breast cancer and poor prognosis. Here, we investigated the levels of IL-8 expression in a variety of breast cancer cells and the regulatory mechanism of IL-8 in triple-negative breast cancer (TNBC) cells. Our results showed that IL-8 expression correlated positively with overall survival in basal-type breast cancer patients. The levels of IL-8 mRNA expression and protein secretion were significantly increased in TNBC cells compared with non-TNBC cells. In addition, the invasiveness of the TNBC cells was dramatically increased by IL-8 treatment and then augmented invasion-related proteins such as matrix metalloproteinase (MMP)-2 or MMP-9. We observed that elevated IL-8 mRNA expression and protein secretion were suppressed by a specific MEK1/2 inhibitor, UO126. In contrast, the overexpression of constitutively active MEK significantly increased the level of IL-8 mRNA expression in BT474 non-TNBC cells. Finally, we investigated the effect of UO126 on the tumorigenecity of TNBC cells. Our results showed that anchorage-independent growth, cell invasion, and cell migration were also decreased by UO126 in TNBC cells. As such, we demonstrated that IL-8 expression is regulated through MEK/ERK-dependent pathways in TNBC cells. A diversity of MEK blockers, including UO126, may be promising for treating TNBC patients.

  17. Comparative actions of progesterone, medroxyprogesterone acetate, drospirenone and nestorone on breast cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Sitruk-Ware Regine

    2008-06-01

    Full Text Available Abstract Background Limited information is available on the effects of progestins on breast cancer progression and metastasis. Cell migration and invasion are central for these processes, and require dynamic cytoskeletal and cell membrane rearrangements for cell motility to be enacted. Methods We investigated the effects of progesterone (P, medroxyprogesterone acetate (MPA, drospirenone (DRSP and nestorone (NES alone or with 17β-estradiol (E2 on T47-D breast cancer cell migration and invasion and we linked some of these actions to the regulation of the actin-regulatory protein, moesin and to cytoskeletal remodeling. Results Breast cancer cell horizontal migration and invasion of three-dimensional matrices are enhanced by all the progestins, but differences are found in terms of potency, with MPA being the most effective and DRSP being the least. This is related to the differential ability of the progestins to activate the actin-binding protein moesin, leading to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. E2 also induces actin remodeling through moesin activation. However, the addition of some progestins partially offsets the action of estradiol on cell migration and invasion of breast cancer cells. Conclusion These results imply that P, MPA, DRSP and NES alone or in combination with E2 enhance the ability of breast cancer cells to move in the surrounding environment. However, these progestins show different potencies and to some extent use distinct intracellular intermediates to drive moesin activation and actin remodeling. These findings support the concept that each progestin acts differently on breast cancer cells, which may have relevant clinical implications.

  18. Quantum dots-based double-color imaging of HER2 positive breast cancer invasion

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiu-Li, E-mail: usually.158@163.com [Department of Oncology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Peng, Chun-Wei, E-mail: pqc278@163.com [Department of Oncology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Chen, Chuang, E-mail: chenc2469@163.com [Department of Oncology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Yang, Xue-Qin, E-mail: yxqjenny@126.com [Department of Oncology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Hu, Ming-Bai, E-mail: humingbai@126.com [Department of Oncology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Xia, He-Shun, E-mail: xiaheshun@yahoo.com.cn [Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei 430079 (China); Liu, Shao-Ping, E-mail: lsp_77@126.com [Department of Oncology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071 (China); and others

    2011-06-10

    Highlights: {yields} HER2 level is closely related to the biologic behaviors of breast cancer cells. {yields} A new method to simultaneously image HER2 and type IV collagen was established. {yields} HER2 status and type IV collagen degradation predict breast cancer invasion. {yields} The complex interactions between tumor and its environment were revealed. -- Abstract: It has been well recognized that human epidermal growth factor receptor 2 (HER2) level in breast cancer (BC) is closely related to the malignant biologic behaviors of the tumor, including invasion and metastasis. Yet, there has been a lack of directly observable evidence to support such notion. Here we report a quantum dots (QDs)-based double-color imaging technique to simultaneously show the HER2 level on BC cells and the type IV collagen in the tumor matrix. In benign breast tumor, the type IV collagen was intact. With the increasing of HER2 expression level, there has been a progressive decrease in type IV collagen around the cancer nest. At HER2 (3+) expression level, there has virtually been a total destruction of type IV collagen. Moreover, HER2 (3+) BC cells also show direct invasion into the blood vessels. This novel imaging method provides direct observable evidence to support the theory that the HER2 expression level is directly related to BC invasion.

  19. Downregulation of microRNA-206 promotes invasion and angiogenesis of triple negative breast cancer.

    Science.gov (United States)

    Liang, Zhongxing; Bian, Xuehai; Shim, Hyunsuk

    2016-08-26

    Triple negative breast tumors don't respond to Tamoxifen and Herceptin, two of the most effective medications for treating breast cancer. Additionally, triple negative breast cancer (TNBC) intrinsically resists or will eventually acquire resistance to chemotherapy. The purpose of this study is to understand better the molecular basis of TNBC as well as develop new therapeutic strategies against it. Here, we analyzed miRNA-206 expression levels in breast cancer cell lines and tissues. In addition, we investigated whether miR-206 mimics inhibited TNBC tumor invasion and angiogenesis. The results showed that miR-206 was downregulated in TNBC compared to non-TNBC cell lines and tissues. Additionally, the decreased levels of miR-206 were inversely consistent with expression levels of VEGF. Furthermore, the forced expression of miR-206 in the mimic-transfected TNBC cells downregulated VEGF, MAPK3, and SOX9 expression levels. The miR-206 mimics inhibited TNBC breast cell invasion and angiogenesis. These findings demonstrate for the first time the involvement of miRNA-206 in TNBC invasion and angiogenesis and suggest that miR-206 may be an efficient agent for therapy of TNBC. PMID:27318091

  20. Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration, Invasion, and In Vivo Invasive Growth Through Targeting C-Met.

    Science.gov (United States)

    Ebrahim, Hassan Y; Elsayed, Heba E; Mohyeldin, Mohamed M; Akl, Mohamed R; Bhattacharjee, Joydeep; Egbert, Susan; El Sayed, Khalid A

    2016-04-01

    Breast cancer is a major health problem affecting the female population worldwide. The triple-negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto-oncogenic receptor tyrosine kinase c-Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c-Met is proposed as a promising candidate target for the control of TNBCs. Lichens-derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen-derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer-guided fractionation of Usnea strigosa (Ach.) lichen extract led to the identification of the depsidone-derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA-MB-231 cell proliferation, migration, and invasion, with minimal toxicity to non-tumorigenic MCF-10A mammary epithelial cells. Molecular modeling, Z'-LYTE biochemical kinase assay and Western blot analysis identified c-Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA-MB-231/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen-derived natural products are promising resources to discover novel c-Met inhibitors useful to control TNBCs. PMID:26744260

  1. Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts.

    Science.gov (United States)

    Al Marzouqi, Nadia; Iratni, Rabah; Nemmar, Abderrahim; Arafat, Kholoud; Ahmed Al Sultan, Mahmood; Yasin, Javed; Collin, Peter; Mester, Jan; Adrian, Thomas E; Attoub, Samir

    2011-10-01

    Breast cancer is a major challenge for pharmacologists to develop new drugs to improve the survival of cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A inhibited the growth of pancreatic cancer cells in vitro and in vivo. We investigated the impact of Frondoside A on human breast cancer cell survival, migration and invasion in vitro, and on tumor growth in nude mice, using the human estrogen receptor-negative breast cancer cell line MDA-MB-231. The non-tumorigenic MCF10-A cell line derived from normal human mammary epithelium was used as control. Frondoside A (0.01-5 μM) decreased the viability of breast cancer cells in a concentration- and time-dependent manner, with 50%-effective concentration (EC50) of 2.5 μM at 24h. MCF10-A cells were more resistant to the cytotoxic effect of Frondoside A (EC50 superior to 5 μM at 24 h). In the MDA-MB-231 cells, Frondoside A effectively increased the sub-G1 (apoptotic) cell fraction through the activation of p53, and subsequently the caspases 9 and 3/7 cell death pathways. In addition, Frondoside A induced a concentration-dependent inhibition of MDA-MB-231 cell migration and invasion. In vivo, Frondoside A (100 μg/kg/dayi.p. for 24 days) strongly decreased the growth of MDA-MB-231 tumor xenografts in athymic mice, without manifest toxic side-effects. Moreover, we found that Frondoside A could enhance the killing of breast cancer cells induced by the chemotherapeutic agent paclitaxel. These findings identify Frondoside A as a promising novel therapeutic agent for breast cancer. PMID:21741966

  2. Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1β dependent upregulation of MYO3A gene in breast cancer cells.

    Science.gov (United States)

    Baghel, Khemraj Singh; Tewari, Brij Nath; Shrivastava, Richa; Malik, Showkat Ahmad; Lone, Mehraj U-Din; Jain, Nem Kumar; Tripathi, Chakrapani; Kanchan, Ranjana Kumari; Dixit, Sameer; Singh, Kavita; Mitra, Kalyan; Negi, Mahendra Pal Singh; Srivastava, Mukesh; Misra, Sanjeev; Bhatt, Madan Lal Brahma; Bhadauria, Smrati

    2016-07-01

    The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or "niche" interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cells with neighboring TAMs actively drive cancer progression and metastatic transformation through intercellular signaling networks that need better elucidation. Thus, current study was planned for discerning paracrine communication networks operational between TAMs, and breast cancer cells with special reference to cancer cell invasion and dissemination to distant sites. Here, we report role of MIP-1β in enhancing invasive potential of metastatic breast cancer MDA-MB-231 and MDA-MB-468 cells. In addition, the poorly metastatic MCF-7 cells were also rendered invasive by MIP-1β. The MIP-1β-driven cancer cell invasion was dependent on upregulated expression levels of MYO3A gene, which encodes an unconventional myosin super-family protein harboring a kinase domain. Ex ovo study employing Chick-embryo-model and in vivo Syngenic 4T1/BALB/c mice-model further corroborated aforementioned in vitro findings, thereby substantiating their physiological relevance. Concordantly, human breast cancer specimen exhibited significant association between mRNA expression levels of MIP-1β and MYO3A. Both, MIP-1β and MYO3A exhibited positive correlation with MMP9, an established molecular determinant of cancer cell invasion. Higher expression of these genes correlated with poor survival of breast cancer patients. Collectively, these results point toward so far undisclosed MIP-1β/MYO3A axis being operational during metastasis, wherein macrophage-derived MIP-1β potentiated cancer cell invasion and metastasis via up regulation of MYO3A gene within cancer cells. Our study exposes opportunities for devising potential anti-metastatic strategies for efficient clinical

  3. Leptin promotes breast cancer cell migration and invasion via IL-18 expression and secretion.

    Science.gov (United States)

    Li, Kuangfa; Wei, Lan; Huang, Yunxiu; Wu, Yang; Su, Min; Pang, Xueli; Wang, Nian; Ji, Feihu; Zhong, Changli; Chen, Tingmei

    2016-06-01

    In recent years, crosstalk between tumor microenvironment and cancer cells have received increasing attention. Accumulating research data suggests that leptin, a key adipokine secreted from adipocytes, plays important roles in breast cancer development. In our study, the effects of leptin on polarization of tumor-associated macrophages (TAMs) and promotion of the invasiveness of tumor cells were investigated. THP1 cells were used to differentiate M2 polarization macrophages. After stimulated by leptin, we established a co-culture system of tumor cells and macrophages to evaluate the function of leptin-induced macrophages in the migration and invasion of breast cancer cells. The gene and protein expressions were analyzed and the underlying mechanisms were evaluated. Moreover, pathological human specimens, and xenografts in nude mice, were detected to strengthen the in vitro results. Leptin elevated the expression of an array of cytokines in TAMs, IL-18 was the most increased, with an activation of the NF-κB/NF-κB1 signalling pathway. Additionally, after treated with leptin, TAMs significantly promoted the migration and invasion of breast cancer cells. However, these effects of leptin were abolished by the co-incubation of Bay11‑7082, a pharmacological NF-κB inhibitor. Leptin also directly stimulated IL-18 expression in breast cancer cells, which, differently, was via the PI3K/AKT-ATF-2 signaling pathway. In vivo studies showed that malignant breast carcinoma exhibited strong higher expression of Leptin, IL-8, and TAMs markers. Xenograft tumor-bearing mouse models showed that leptin significantly increased tumor volume, enhanced lung metastases, and increased expression of IL-8 and TAM markers, which were abolished by depletion of macrophages by clophosome-clodronate liposomes (CCL). Leptin could induce IL-18 expression both in TAMs and breast cancer cells. Leptin-induced IL-18 expression was regulated via NF-κB/NF-κB1 signaling in TAMs, while via PI3K

  4. Leptin promotes breast cancer cell migration and invasion via IL-18 expression and secretion.

    Science.gov (United States)

    Li, Kuangfa; Wei, Lan; Huang, Yunxiu; Wu, Yang; Su, Min; Pang, Xueli; Wang, Nian; Ji, Feihu; Zhong, Changli; Chen, Tingmei

    2016-06-01

    In recent years, crosstalk between tumor microenvironment and cancer cells have received increasing attention. Accumulating research data suggests that leptin, a key adipokine secreted from adipocytes, plays important roles in breast cancer development. In our study, the effects of leptin on polarization of tumor-associated macrophages (TAMs) and promotion of the invasiveness of tumor cells were investigated. THP1 cells were used to differentiate M2 polarization macrophages. After stimulated by leptin, we established a co-culture system of tumor cells and macrophages to evaluate the function of leptin-induced macrophages in the migration and invasion of breast cancer cells. The gene and protein expressions were analyzed and the underlying mechanisms were evaluated. Moreover, pathological human specimens, and xenografts in nude mice, were detected to strengthen the in vitro results. Leptin elevated the expression of an array of cytokines in TAMs, IL-18 was the most increased, with an activation of the NF-κB/NF-κB1 signalling pathway. Additionally, after treated with leptin, TAMs significantly promoted the migration and invasion of breast cancer cells. However, these effects of leptin were abolished by the co-incubation of Bay11‑7082, a pharmacological NF-κB inhibitor. Leptin also directly stimulated IL-18 expression in breast cancer cells, which, differently, was via the PI3K/AKT-ATF-2 signaling pathway. In vivo studies showed that malignant breast carcinoma exhibited strong higher expression of Leptin, IL-8, and TAMs markers. Xenograft tumor-bearing mouse models showed that leptin significantly increased tumor volume, enhanced lung metastases, and increased expression of IL-8 and TAM markers, which were abolished by depletion of macrophages by clophosome-clodronate liposomes (CCL). Leptin could induce IL-18 expression both in TAMs and breast cancer cells. Leptin-induced IL-18 expression was regulated via NF-κB/NF-κB1 signaling in TAMs, while via PI3K

  5. Protein tyrosine phosphatase controls breast cancer invasion through the expression of matrix metalloproteinase-9

    Directory of Open Access Journals (Sweden)

    Bo-Mi Hwang

    2013-11-01

    Full Text Available The expression of matrix metalloproteinases (MMPs produced bycancer cells has been associated with the high potential ofmetastasis in several human carcinomas, including breast cancer.Several pieces of evidence demonstrate that protein tyrosinephosphatases (PTP have functions that promote cell migrationand metastasis in breast cancer. We analyzed whether PTPinhibitor might control breast cancer invasion through MMPexpression. Herein, we investigate the effect of 4-hydroxy-3,3-dimethyl-2H benzo[g]indole-2,5(3H-dione (BVT948, anovel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate(TPA-induced MMP-9 expression and cell invasion in MCF-7cells. The expression of MMP-9 and cell invasion increased afterTPA treatment, whereas TPA-induced MMP-9 expression and cellinvasion were decreased by BVT948 pretreatment. Also, BVT948suppressed NF-κB activation in TPA-treated MCF-7 cells.However, BVT948 didn’t block TPA-induced AP-1 activation inMCF-7 cells. Our results suggest that the PTP inhibitor blocksbreast cancer invasion via suppression of the expression ofMMP-9. [BMB Reports 2013; 46(11: 533-538

  6. Predictive factors of the survival of women with invasive breast cancer in French Guiana: the burden of health inequalities

    OpenAIRE

    Roué, Tristan; Labbé, Sylvain; Belliardo, Sophie; Plenet, Juliette; Douine, Maylis; Nacher, Mathieu

    2016-01-01

    International audience; This study aimed to compare the relative survival of patients with invasive breast cancer between women from French Guiana (a French territory in South America) and metropolitan France. No study hadever compared survival of breast cancer on the basis of immigrant status in France. Our study underlined that access to care for migrants is challenging whichwgenerates health inequalities. Background The prognosis of breast cancer in French Guiana is worse than in France wi...

  7. Patients with Invasive Lobular Breast Cancer Are Less Likely to Undergo Breast-Conserving Surgery: A Population Based Study in The Netherlands

    NARCIS (Netherlands)

    Truin, W.; Roumen, R.M.; Siesling, S.; Heiden-van der Loo, van der M.; Duijm, E.M.; Tjan-Heijnen, V.C.G.; Voogd, A.C.

    2015-01-01

    Purpose The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC). Methods Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from th

  8. Expression of glucosylceramide synthase in invasive ductal breast cancer may be correlated with high estrogen receptor status and low HER-2 status

    OpenAIRE

    Liu, Jiannan; Sun, Ping; Sun, Yuan; Liu, Aina; You, Dong; Jiang, Fenge; Sun, Yuping

    2014-01-01

    Abstract Background and objectives Breast cancer is one of the most common causes of cancer-related deaths in women worldwide. Studies on glucosylceramide synthase (GCS) activity suggest that this enzyme has a role in the development of multidrug resistance in many cancer cells. However, few studies have shown the expression of GCS in invasive ductal breast cancer and breast intraductal proliferative lesions. Methods In total, 196 samples from patients with invasive ductal breast cancer and 6...

  9. Development of a novel approach for breast cancer prediction and early detection using minimally invasive procedures and molecular analysis: how cytomorphology became a breast cancer risk predictor.

    Science.gov (United States)

    Masood, Shahla

    2015-01-01

    With enhanced public awareness, advances in breast imaging, and emphasis on early breast cancer detection and prevention, more women are seeking consultation to assess the status of their breast health. Risk assessment has become an integral part of established multi-disciplinary breast care, and breast cancer risk reduction interventions have received a great deal of attention. Similarly, interest in identification of high-risk individuals has increased significantly. Atypical proliferative changes in breast epithelial cells are ranked high among various known breast cancer risk factors and, in recent years, have been the subject of several investigations. Breast tissue and fluid in the ductal system provide a rich source of cells and biomarkers that have the potential to aid in the assessment of short-term risk of breast cancer development, and assess responses to interventional prevention efforts. There are three minimally invasive procedures currently being utilized to sample breast tissue in asymptomatic high-risk individuals. These procedures are: fine-needle aspiration biopsy, nipple aspiration fluid, and ductal lavage. In this review article, the merits and limitations of each procedure are presented, and the contribution of cytomorphology and molecular analysis in breast cancer prediction is highlighted. In addition, the role of Masood Cytology Index as a surrogate endpoint biomarker in chemopreventative trials is discussed. PMID:25556774

  10. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice

    International Nuclear Information System (INIS)

    Highlights: ► This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. ► Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. ► TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. ► TIP-1 knockdown suppressed the expression and functionality of motility-related genes. -- Abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.

  11. The Runx transcriptional co-activator, CBFβ, is essential for invasion of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Lopez-Camacho Cesar

    2010-06-01

    Full Text Available Abstract Background The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFβ is a transcriptional co-activator that is recruited to promoters by Runx transcription factors and there is considerable evidence that CBFβ is essential for the function of Runx factors. However, overexpression of Runx1 can partially rescue the lethal phenotype in CBFβ-deficient mice, indicating that increased levels of Runx factors can, in some situations, overcome the requirement for CBFβ. Since Runx2 is overexpressed in metastatic breast cancer cells, and there are no reports of CBFβ expression in breast cells, we sought to determine whether Runx2 function in these cells was dependent on CBFβ. Such an interaction might represent a viable target for therapeutic intervention to inhibit bone metastasis. Results We show that CBFβ is expressed in the metastatic breast cancer cells, MDA-MB-231, and that it associates with Runx2. Matrigel invasion assays and RNA interference were used to demonstrate that CBFβ contributes to the invasive capacity of these cells. Subsequent analysis of Runx2 target genes in MDA-MB-231 cells revealed that CBFβ is essential for the expression of Osteopontin, Matrixmetalloproteinase-13, Matrixmetalloproteinase-9, and Osteocalcin but not for Galectin-3. Chromatin immunoprecipitation analysis showed that CBFβ is recruited to both the Osteopontin and the Galectin-3 promoters. Conclusions CBFβ is expressed in metastatic breast cancer cells and is essential for cell invasion. CBFβ is required for expression of several Runx2-target genes known to be involved in cell invasion. However, whilst CBFβ is essential for invasion, not all Runx2-target genes require CBFβ. We conclude that CBFβ is required for a subset of Runx2-target genes

  12. Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features

    International Nuclear Information System (INIS)

    Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a pro-apoptotic member of the Bcl-2 family induced under hypoxia. Low or absent expression has recently been described in human tumors, including gastrointestinal tumors, resulting in poor prognosis. Little is known about BNIP3 expression in invasive breast cancer. The aim of the present study was to investigate the expression of BNIP3 in invasive breast cancer at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features. In 40 cases of invasive breast cancer, BNIP3 mRNA in situ hybridization was performed on frozen sections with a digoxigenin labeled anti-BNIP3 probe. Paraffin embedded sections of the same specimens were used to determine protein expression of BNIP3, Hypoxia Inducible Factor 1 alpha (HIF-1α) and its downstream targets Glucose Transporter 1 (Glut-1) and Carbonic Anhydrase (CAIX) by immunohistochemistry. BNIP3 mRNA was expressed in 16/40 (40%) of the cases and correlated with BNIP3 protein expression (p = 0.0218). Neither BNIP3 protein nor mRNA expression correlated with expression of HIF-1α expression or its downstream targets. Tumors which showed loss of expression of BNIP3 had significantly more often lymph node metastases (82% vs 39%, p = 0.010) and showed a higher mitotic activity index (p = 0.027). BNIP3 protein expression was often nuclear in normal breast, but cytoplasmic in tumor cells. BNIP3 expression is lost in a significant portion of invasive breast cancers, which is correlated with poor prognostic features such as positive lymph node status and high proliferation, but not with the hypoxic response

  13. Ets-1 controls breast cancer cell balance between invasion and growth.

    Science.gov (United States)

    Furlan, Alessandro; Vercamer, Chantal; Bouali, Fatima; Damour, Isabelle; Chotteau-Lelievre, Anne; Wernert, Nicolas; Desbiens, Xavier; Pourtier, Albin

    2014-11-15

    Ets-1 overexpression in human breast cancers is associated with invasiveness and poor prognosis. By overexpressing Ets-1 or a dominant negative mutant in MMT breast cancer cells, we previously highlighted the key role of Ets-1 in coordinating multiple invasive features of these cells. Interestingly, we also noticed that Ets-1 decreased the density of breast cancer cells cultured in three-dimensional extracellular matrix gels. The 3D context was instrumental to this phenomenon, as such downregulation was not observed in cells grown on two-dimensional plastic or matrix-coated dishes. Ets-1 overexpression was deleterious to anchorage-independent growth of MMT cells in soft agar, a standard model for in vitro tumorigenicity. The relevance of this mechanism was confirmed in vivo, during primary tumor growth and in a metastatic assay of lung colonization. In these models, Ets-1 was associated with epithelial-to-mesenchymal transition features and modulated the ratio of Ki67-positive cells, while hardly affecting in vivo apoptotic cell death. Finally, siRNA-mediated knockdown of Ets-1 in human breast cancer cell lines also decreased colony growth, both in anchorage-independent assays and 3D extracellular matrix cultures. These in vitro and in vivo observations shed light on an unsuspected facet of Ets-1 in breast tumorigenesis. They show that while promoting malignancy through the acquisition of invasive features, Ets-1 also attenuates breast tumor cell growth and could therefore repress the growth of primary tumors and metastases. This work also demonstrates that 3D models may reveal mechanisms of tumor biology that are cryptic in standard 2D models.

  14. Functional characterization of E- and P-cadherin in invasive breast cancer cells

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    Cano Amparo

    2009-03-01

    Full Text Available Abstract Background Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. Methods To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. Results Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. Conclusion E- and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer.

  15. High Expression of the RECK Gene in Breast Cancer Cells is Related to Low Invasive Capacity

    Institute of Scientific and Technical Information of China (English)

    Tao Sun; Daqing Jiang; Jinming Li; Dongyun Han; Zhiguo Song

    2006-01-01

    OBJECTIVE To investigate the expression of the RECK gene in human breast (cancer) cell lines, and to determine the relationship between RECK gene expression and the invasive capacity of the breast cancer cell lines.METHODS The invasive capacity of breast (cancer) cell lines including HBL-100, MCF-7 and MDA-MB-435S were determined by the Transwell method. The protein expression levels of RECK, MMP-2 and MMP- 9 genes in these three cell lines were measured by immunocytochemical methods. The expressions of the RECK gene and protein level were measured by RT-PCR and Western blots in the cell lines respectively.RESULTS The order of the invasive capacity of the breast (cancer) cell lines was MDA-MB-435S, being the highest, and HBL-100, being the lowest. The invasive capacity difference between any two groups among the three groups was significant (P<0.01). The protein expression level of the RECK gene in the HBL-100 cell line was highest, and no expression was detected in MDA-MB-435S cells. Moreover, the expression of the RECK gene was negatively correlated with the expression of the MMP-2 and MMP-9 genes. The mRNA level of the RECK gene in HBL-100 cells was the highest, but no expression was found in the MDA-MB-435S cells (P<0.001).CONCLUSION There was a significant negative correlation between the expression level of the RECK gene and invasive capacity in vitro, and the RECK gene expression showed an inverse proportion to that of the MMP-2, MMP-9 genes.

  16. VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fanni; Li, Chenglin; Zhang, Haiwei; Lu, Zhijian [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China); Li, Zhiyu; You, Qidong [Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Lu, Na [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China); Guo, Qinglong, E-mail: anticancer_drug@yahoo.com.cn [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China)

    2012-06-01

    It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Western blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy. Highlights: ► We report for the first time that VI-14 possesses anti-cancer properties. ► VI-14 weakens the adhesion, migration and invasion of human breast cancer cells. ► VI-14 decreases the activities and expressions of MMP-2/9. ► VI-14 suppresses the phosphorylation levels of the MAPK signaling pathway. ► VI-14 decreases the nuclear levels and the binding ability of NF-κB and AP-1.

  17. RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13.

    Directory of Open Access Journals (Sweden)

    Ila Datar

    Full Text Available Raf Kinase Inhibitory Protein or RKIP was initially identified as a Raf-1 binding protein using the yeast 2-hybrid screen. RKIP inhibits the activation phosphorylation of MEK by Raf-1 by competitively inhibiting the binding of MEK to Raf-1 and thus exerting an inhibitory effect on the Raf-MEK-Erk pathway. RKIP has been identified as a metastasis suppressor gene. Expression of RKIP is low in cancer metastases. Although primary tumor growth remains unaffected, re- expression of RKIP inhibits cancer metastasis. Mechanistically, RKIP constrains metastasis by inhibiting angiogenesis, local invasion, intravasation, and colonization. The molecular mechanism of how RKIP inhibits these individual steps remains undefined. In our present study, using an unbiased PCR based screening and by analyzing DNA microarray expression datasets we observe that the expression of multiple metalloproteases (MMPs including MMP1, MMP3, MMP10 and MMP13 are negatively correlated with RKIP expression in breast cancer cell lines and clinical samples. Since expression of MMPs by cancer cells is important for cancer metastasis, we hypothesize that RKIP may mediate suppression of breast cancer metastasis by inhibiting multiple MMPs. We show that the expression signature of RKIP and MMPs is better at predicting high metastatic risk than the individual gene. Using a combination of loss- and gain-of-function approaches, we find that MMP13 is the cause of RKIP-mediated inhibition of local cancer invasion. Interestingly expression of MMP13 alone is not sufficient to reverse the inhibition of breast cancer cell metastasis to the lung due to the expression of RKIP. We find that RKIP negatively regulates MMP13 through the Erk2 signaling pathway and the repression of MMP13 by RKIP is transcription factor AP-1 independent. Together, our findings indicate that RKIP inhibits cancer cell invasion, in part, via MMP13 inhibition. These data also implicate RKIP in the regulation of MMP

  18. Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in breast cancer invasion.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available Dysregulation of Ras and Rho family small GTPases drives the invasion and metastasis of multiple cancers. For their biological functions, these GTPases require proper subcellular localization to cellular membranes, which is regulated by a series of post-translational modifications that result in either farnesylation or geranylgeranylation of the C-terminal CAAX motif. This concept provided the rationale for targeting farnesyltransferase (FTase and geranylgeranyltransferases (GGTase for cancer treatment. However, the resulting prenyl transferase inhibitors have not performed well in the clinic due to issues with alternative prenylation and toxicity. As an alternative, we have developed a unique class of potential anti-cancer therapeutics called Prenyl Function Inhibitors (PFIs, which are farnesol or geranyl-geraniol analogs that act as alternate substrates for FTase or GGTase. Here, we test the ability of our lead PFIs, anilinogeraniol (AGOH and anilinofarnesol (AFOH, to block the invasion of breast cancer cells. We found that AGOH treatment effectively decreased invasion of MDA-MB-231 cells in a two-dimensional (2D invasion assay at 100 µM while it blocked invasive growth in three-dimensional (3D culture model at as little as 20 µM. Notably, the effect of AGOH on 3D invasive growth was phenocopied by electroporation of cells with C3 exotransferase. To determine if RhoA and RhoC were direct targets of AGOH, we performed Rho activity assays in MDA-MB-231 and MDA-MB-468 cells and found that AGOH blocked RhoA and RhoC activation in response to LPA and EGF stimulation. Notably, the geranylgeraniol analog AFOH was more potent than AGOH in inhibiting RhoA and RhoC activation and invasive growth. Interestingly, neither AGOH nor AFOH impacted 3D growth of MCF10A cells. Collectively, this study demonstrates that AGOH and AFOH dramatically inhibit breast cancer invasion, at least in part by blocking Rho function, thus, suggesting that targeting

  19. 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 ...

  20. Can high frequency ultrasound predict metastatic lymph nodes in patients with invasive breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Clough, Gillian R. [University of Bradford, Unity Building, 25 Trinity Road, Bradford BD5 0BB (United Kingdom)]. E-mail: g.r.clough@bradford.ac.uk; Truscott, John [University of Leeds (United Kingdom); Haigh, Isobel [Leeds Teaching Hospitals NHS Trust (United Kingdom)

    2006-05-15

    Purpose: Use high frequency ultrasound to predict the presence of metastatic axillary lymph nodes, with a high specificity and positive predictive value, in patients with invasive breast cancer. The clinical aim is to improve the surgical management and possible survival rate of groups of patients who would not normally have conventional axillary dissections. Materials and methods: The ipsilateral and contralateral axillas of 42 consecutive patients with invasive breast cancer were scanned prior to treatment using a B-mode frequency of 13 MHz and a Doppler frequency of 7 MHz. The presence or absence of an echogenic centre for each lymph node detected was recorded, measurements were also taken to determine the L/S (long axis/short axis) ratio of the node and the widest and narrowest part of the cortex. Power Doppler was also used to determine vascularity. The contralateral axilla was used as a control for each patient. Results: In this study of patients with invasive breast cancer, where ipsilateral lymph nodes had a cortical bulge of {>=}3 mm and/or at least two lymph nodes had absent echogenic centres, all had disease spread to the axillary lymph nodes (10 patients). Sensitivity and specificity were 52.6% and 100%, respectively, positive and negative predictive values were 100% and 71.9%, respectively, the P-value was 0.001 and the Kappa score was 0.55. Conclusion: This would indicate that high frequency ultrasound could be used to accurately predict metastatic lymph nodes in a proportion of patients with invasive breast cancer, which may alter patient management.

  1. Relationship between CYP1A1 polymorphisms and invasion and metastasis of breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hua Wang; Wen-Jian Wang

    2013-01-01

    Objective:To investigate the relationship betweenCYP1A1 genetic polymorphisms and the invasion and metastasis of breast cancer.Methods:TheCYP1A1 gene polymorphism(anT-C transversion at nucleotide position3801) was detected by the polymerase chain reaction and restriction fragment length polymorphism in80 cases with breast cancer and60 samples of normal breast tissue.The difference in genotypic distribution frequency between the groups, the correlation between the genotypes and the factors related to prognosis were analyzed.Results:The incidence of homozygous and variant genotypes had no difference between the breast cancer group and controls group(P=0.746).The proportion of variant genotype increased as clinical stage(P=0.006) advanced, as well as with increased numbers of lymph node metastases(P=0.010). Conclusions:In patients with breast cancer there is a correlation between theCYP1A1CC allele and some factors indicating poor prognosis, including more lymph node metastases as well as a more advanced clinical stage.

  2. 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

  3. MicroRNA-124 inhibits cellular proliferation and invasion by targeting Ets-1 in breast cancer.

    Science.gov (United States)

    Li, Wentao; Zang, Wenqiao; Liu, Pei; Wang, Yuanyuan; Du, Yuwen; Chen, Xiaonan; Deng, Meng; Sun, Wencong; Wang, Lei; Zhao, Guoqiang; Zhai, Baoping

    2014-11-01

    MicroRNAs (miRNAs) are small non-coding RNAs that, by targeting certain messenger RNAs (mRNAs) for translational repression or cleavage, can regulate the expression of these genes. In addition, miRNAs may also function as oncogenes and tumor-suppressor genes, as the abnormal expression of miRNAs is associated with various human tumors. However, the effects of the expression of miR-124 in breast cancer remain unclear. The present study was conducted to study the expression of miR-124 in breast cancer, paying particular attention to miR-124's relation to the proliferation, invasion, and apoptosis in breast cancer cell MCF-7 and MDA-MB-231. Real-time quantitative RT-PCR (qRT-PCR) was performed to identify miR-124 that was down-regulated in breast cancer tissues. We also showed E26 transformation specific-1 (Ets-1) and miR-124 expression levels in breast cancer tissues that were associated with lymph node metastases. With transfected synthetic miR-124 agomir into MCF-7 and MDA-MB-231, a significant reduction (P Ets-1 as a potential major target gene of miR-124, and the result showed that miR-124 can bind to putative binding sites within the Ets-1 mRNA 3' untranslated region (UTR) to reduce its expression. Based on these findings, we propose that miR-124 and Ets-1 may serve as a therapeutic agent in breast cancer.

  4. Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Z. N.; Sharma, V. P.; Beaty, B. T.; Roh-Johnson, M.; Peterson, E. A.; Van Rooijen, N.; Kenny, P. A.; Wiley, H. S.; Condeelis, J. S.; Segall, J. E.

    2014-10-13

    Increased expression of HBEGF in estrogen receptor-negative breast tumors is correlated with enhanced metastasis to distant organ sites and more rapid disease recurrence upon removal of the primary tumor. Our previous work has demonstrated a paracrine loop between breast cancer cells and macrophages in which the tumor cells are capable of stimulating macrophages through the secretion of colony-stimulating factor-1 while the tumor-associated macrophages (TAMs), in turn, aid in tumor cell invasion by secreting epidermal growth factor. To determine how the autocrine expression of epidermal growth factor receptor (EGFR) ligands by carcinoma cells would affect this paracrine loop mechanism, and in particular whether tumor cell invasion depends on spatial ligand gradients generated by TAMs, we generated cell lines with increased HBEGF expression. We found that autocrine HBEGF expression enhanced in vivo intravasation and metastasis and resulted in a novel phenomenon in which macrophages were no longer required for in vivo invasion of breast cancer cells. In vitro studies revealed that expression of HBEGF enhanced invadopodium formation, thus providing a mechanism for cell autonomous invasion. The increased invadopodium formation was directly dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of signaling downstream of EGFR activation. HBEGF expression also resulted in enhanced invadopodium function via upregulation of matrix metalloprotease 2 (MMP2) and MMP9 expression levels. We conclude that high levels of HBEGF expression can short-circuit the tumor cell/macrophage paracrine invasion loop, resulting in enhanced tumor invasion that is independent of macrophage signaling.

  5. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    Science.gov (United States)

    2016-07-12

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  6. Our approach for breast cancer screening using both mammography and echography, with special reference to detection of nonpalpable minute invasive cancer

    International Nuclear Information System (INIS)

    We present the results of our approach for breast cancer screening using both mammography and echography. A total of 4,632 participants underwent screening with our own combined method using mammography and echography at our clinic during a two-year period in 2005 and 2006. Recall studies were carried out in 364 women (recall rate, 79%), and breast cancer was detected in 36 women (cancer detection rate, 0.78%). When the detected cancers were classified histopathologically, 22 were invasive ductal cancers and the remaining 14 were non-invasive cancers. Of the 22 women who proved to have invasive cancers, 14 had been unaware of their tumors, which were non-palpable. If an invasive cancer is overlooked, the consequences may be more serious than if a non-invasive cancer is missed, because the former is can be potentially fatal. In order to decrease breast cancer mortality, invasive cancers must be detected when they are small. Since we were able to detect many small and non-palpable breast cancers that had not been noticed by the participants, our current breast cancer screening system appears to be more efficient for life-saving than other systems. (author)

  7. Myoferlin depletion in breast cancer cells promotes mesenchymal to epithelial shape change and stalls invasion.

    Directory of Open Access Journals (Sweden)

    Ruth Li

    Full Text Available Myoferlin (MYOF is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode protein that regulates spermatic membrane fusion, which underlies the amoeboid-like movements of its sperm. Studies in muscle and endothelial cells have reported on the role of myoferlin in membrane repair, endocytosis, myoblast fusion, and the proper expression of various plasma membrane receptors. In this study, using an in vitro human breast cancer cell model, we demonstrate that myoferlin is abundantly expressed in invasive breast tumor cells. Depletion of MYOF using lentiviral-driven shRNA expression revealed that MDA-MB-231 cells reverted to an epithelial morphology, suggesting at least some features of mesenchymal to epithelial transition (MET. These observations were confirmed by the down-regulation of some mesenchymal cell markers (e.g., fibronectin and vimentin and coordinate up-regulation of the E-cadherin epithelial marker. Cell invasion assays using Boyden chambers showed that loss of MYOF led to a significant diminution in invasion through Matrigel or type I collagen, while cell migration was unaffected. PCR array and screening of serum-free culture supernatants from shRNA(MYOF transduced MDA-MB-231 cells indicated a significant reduction in the steady-state levels of several matrix metalloproteinases. These data when considered in toto suggest a novel role of MYOF in breast tumor cell invasion and a potential reversion to an epithelial phenotype upon loss of MYOF.

  8. DEGRO practical guidelines: radiotherapy of breast cancer II. Radiotherapy of non-invasive neoplasia of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Souchon, R. [University Hospital Tuebingen, Klinik fuer Radioonkologie, Tuebingen (Germany); Sautter-Bihl, M.L. [Municipal Hospital Karlsruhe, Karlsruhe (Germany); Sedlmayer, F. [LKH Salzburg, Paracelsus Medical University Hospital, Salzburg (Austria); Budach, W. [University Hospital Duesseldorf, Duesseldorf (Germany); Dunst, J. [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, P. [Klinikum Neukoelln, Berlin (Germany); Fietkau, R.; Sauer, R. [University Hospital Erlangen, Erlangen (Germany); Harms, W. [St. Clara Hospital, Basel (Switzerland); Wenz, F. [University Hospital Mannheim, Mannheim (Germany); Haase, W.

    2014-01-15

    To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''non invasive breast cancer'', ''ductal carcinoma in situ, ''dcis'', ''borderline breast lesions'', ''lobular neoplasia'', ''radiotherapy'' and ''radiation therapy''. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy

  9. Silencing of SOX12 by shRNA suppresses migration, invasion and proliferation of breast cancer cells

    Science.gov (United States)

    Ding, Hanzhi; Quan, Hong; Yan, Weiguo; Han, Jing

    2016-01-01

    Sex determining region Y-box protein 12 (SOX12) is essential for embryonic development and cell-fate determination. The role of SOX12 in tumorigenesis of breast cancer is not well-understood. Here, we found that SOX12 mRNA expression was up-regulated in human breast cancer tissues. To clarify the roles of SOX12 in breast cancer, we used lentiviral shRNAs to suppress its expression in two breast cancer cells with relatively higher expression of SOX12 (BT474 and MCF-7). Our findings strongly suggested that SOX12 was critical for cell migration and invasion of breast cancer cells. We found that silencing of SOX12 significantly decreased the mRNA and protein levels of MMP9 and Twist, while notably increased E-cadherin. Moreover, SOX12 knockdown significantly inhibited the proliferation of breast cancer cells in vitro and the growth of xenograft tumours in vivo. Flow cytometry analysis revealed that breast cancer cells with SOX12 knockdown showed cell cycle arrest and decreased mRNA and protein levels of proliferating cell nuclear antigen (PCNA), CDK2 and Cyclin D1. Taken together, SOX12 plays an important role in growth inhibition through cell-cycle arrest, as well as migration and invasion of breast cancer cells. PMID:27582508

  10. Radiation therapy and chemotherapy after breast conserving surgery for invasive breast cancer: an intermediate result

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seok Ho; Lee, Kyu Chan; Choi, Jin Ho; Lee, Young Don; Park, Heoung Kyu; Kim, Hyun Young; Park, Se Hoon [Gachon Medical School, Incheon (Korea, Republic of)

    2007-03-15

    Breast conserving surgery (BCS) followed by chemotherapy (CT{sub x}.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, 27 {approx} 76 years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection, BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An additional dose of 9 {approx} 16 Gy was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CT{sub x}. with 4 {approx} 6 cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: 17 {approx} 93 months). The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five

  11. Ascertaining invasive breast cancer cases; the validity of administrative and self-reported data sources in Australia

    OpenAIRE

    Kemp, Anna; Preen, David B; Saunders, Christobel; Holman, C. D’Arcy J.; Bulsara, Max; Rogers, Kris; Roughead, Elizabeth E.

    2013-01-01

    Background Statutory State-based cancer registries are considered the ‘gold standard’ for researchers identifying cancer cases in Australia, but research using self-report or administrative health datasets (e.g. hospital records) may not have linkage to a Cancer Registry and need to identify cases. This study investigated the validity of administrative and self-reported data compared with records in a State-wide Cancer Registry in identifying invasive breast cancer cases. Methods Cases of inv...

  12. miR-199a-5p regulates β1 integrin through Ets-1 to suppress invasion in breast cancer.

    Science.gov (United States)

    Li, Wentong; Wang, Hui; Zhang, Jinbao; Zhai, Limin; Chen, Weijuan; Zhao, Chunling

    2016-07-01

    Increasing evidence has revealed that miR-199a-5p is actively involved in tumor invasion and metastasis as well as in the decline of breast cancer tissues. In this research, overexpression of miR-199a-5p weakened motility and invasion of breast cancer cells MCF-7 and MDA-MB-231. Upregulation of Ets-1 increased breast cancer cell invasion, but the mechanism by which miR-199a-5p modulates activation of Ets-1 in breast cancer was not clarified. We investigated the relationship between miR-199a-5p and Ets-1 on the basis of 158 primary breast cancer case specimens, and the results showed that Ets-1 expression was inversely correlated with endogenous miR-199a-5p. Overexpression of miR-199a-5p reduced the mRNA and protein levels of Ets-1 in MCF-7 and MDA-MB-231 cells, whereas anti-miR-199a-5p elevated Ets-1. siRNA-mediated Ets-1 knockdown phenocopied the inhibition invasion of miR-199a-5p in vitro. Moreover, luciferase reporter assay revealed that miR-199a-5p directly targeted 3'-UTR of Ets-1 mRNA. This research revealed that miR-199a-5p could descend the levels of β1 integrin by targeting 3'-UTR of Ets-1 to alleviate the invasion of breast cancer via FAK/Src/Akt/mTOR signaling pathway. Our results provide insight into the regulation of β1 integrin through miR-199a-5p-mediated Ets-1 silence and will help in designing new therapeutic strategies to inhibit signal pathways induced by miR-199a-5p in breast cancer invasion.

  13. Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells.

    Science.gov (United States)

    Price, D J; Miralem, T; Jiang, S; Steinberg, R; Avraham, H

    2001-03-01

    The expression of vascular endothelial growth factor (VEGF) by breast tumors has been previously correlated with a poor prognosis in the pathogenesis of breast cancer. Furthermore, VEGF secretion is a prerequisite for tumor development. Although most of the effects of VEGF have been shown to be attributable to the stimulation of endothelial cells, we present evidence here that breast tumor cells are capable of responding to VEGF. We show that VEGF stimulation of T-47D breast cancer cells leads to changes in cellular signaling and invasion. VEGF increases the cellular invasion of T-47D breast cancer cells on Matrigel/ fibronectin-coated transwell membranes by a factor of two. Northern analysis for the expression of the known VEGF receptors shows the presence of moderate levels of Flt-1 and low levels of Flk-1/KDR mRNAs in a variety of breast cancer cell lines. T-47D breast cancer cells bind 125I-labeled VEGF with a Kd of 13 x 10(-9) M. VEGF induces the activation of the extracellular regulated kinases 1,2 as well as activation of phosphatidylinositol 3'-kinase, Akt, and Forkhead receptor L1. These findings in T-47D breast cancer cells strongly suggest an autocrine role for VEGF contributing to the tumorigenic phenotype.

  14. Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

    Science.gov (United States)

    2016-02-09

    Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

  15. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

    OpenAIRE

    Dharmawardhane Suranganie F; Wall Kristin M; Hoffmeyer Michaela R

    2005-01-01

    Abstract Background Inflammatory breast cancer (IBC) is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. Results Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive prop...

  16. Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor.

    Science.gov (United States)

    Sheffield, Brandon S; Kos, Zuzana; Asleh-Aburaya, Karama; Wang, Xiu Qing; Leung, Samuel; Gao, Dongxia; Won, Jennifer; Chow, Christine; Rachamadugu, Rakesh; Stijleman, Inge; Wolber, Robert; Gilks, C Blake; Myles, Nickolas; Thomson, Tom; Hayes, Malcolm M; Bernard, Philip S; Nielsen, Torsten O; Chia, Stephen K L

    2016-02-01

    The estrogen receptor (ER) is a key predictive biomarker in the treatment of breast cancer. There is uncertainty regarding the use of hormonal therapy in the setting of weakly positive ER by immunohistochemistry (IHC). We report intrinsic subtype classification on a cohort of ER weakly positive early-stage breast cancers. Consecutive cases of breast cancer treated by primary surgical resection were retrospectively identified from 4 centers that engage in routine external proficiency testing for breast biomarkers. ER-negative (Allred 0 and 2) and ER weakly positive (Allred 3-5) cases were included. Gene expression profiling was performed using qRT-PCR. Intrinsic subtype prediction was made based upon the PAM50 gene expression signature. 148 cases were included in the series: 60 cases originally diagnosed as ER weakly positive and 88 ER negative. Of the cases originally assessed as ER weakly positive, only 6 (10 %) were confirmed to be of luminal subtype by gene expression profiling; the remaining 90 % of cases were classified as basal-like or HER2-enriched subtypes. This was not significantly different than the fraction of luminal cases identified in the IHC ER-negative cohort (5 (5 %) luminal, 83(95 %) non-luminal). Recurrence-free, and overall, survival rates were similar in both groups (p = 0.4 and 0.5, respectively) despite adjuvant hormonal therapy prescribed in the majority (59 %) of weakly positive ER cases. Weak ER expression by IHC is a poor correlate of luminal subtype in invasive breast cancer. In the setting of highly sensitive and robust IHC methodology, cutoffs for ER status determination and subsequent systemic therapy should be revisited. PMID:26846986

  17. Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms

    DEFF Research Database (Denmark)

    Law, M E; Corsino, P E; Jahn, S C;

    2013-01-01

    cells are a frequently used model of invasive triple-negative breast cancer, and these cells express low levels of E-cadherin that is mislocalized to cytoplasmic vesicles. MDA-MB-231 cell lines stably expressing wild-type E-cadherin or E-cadherin fused to glutathione S-transferase or green fluorescent...... protein were used as experimental systems to probe the mechanisms responsible for cytoplasmic E-cadherin localization in invasive cancers. Although E-cadherin expression partly reduced cell invasion in vitro, E-cadherin was largely localized to the cytoplasm and did not block the invasiveness......Aggressive cancers often express E-cadherin in cytoplasmic vesicles rather than on the plasma membrane and this may contribute to the invasive phenotype of these tumors. Therapeutic strategies are not currently available that restore the anti-invasive function of E-cadherin in cancers. MDA-MB-231...

  18. Suppression of cell growth and invasion by miR-205 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hailong Wu; Shoumin Zhu; Yin-Yuan Mo

    2009-01-01

    MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB-231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR-205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A (VEGF-A) are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3'-untranslated region (3'-UTR) of ErbB3 and VEGF-A. Together, these results suggest that miR-205 is a tumor suppressor in breast cancer.

  19. G12 Signaling through c-Jun NH2-Terminal Kinase Promotes Breast Cancer Cell Invasion

    OpenAIRE

    Juhi Juneja; Ian Cushman; Casey, Patrick J.

    2011-01-01

    Signaling through the heterotrimeric G protein, G12, via Rho induces a striking increase in breast cancer cell invasion. In this study, evidence is provided that the c-Jun NH(2)-terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Expression of constitutively-active Gα12 or activation of G12 signaling by thrombin leads to increased JNK and c-Jun phosphorylation. Pharmacologic inhibition of JNK or knockdown of JNK expression by siRNA significantly decreases G12-induced JN...

  20. Inorganic sulfur reduces the motility and invasion of MDA-MB-231 human breast cancer cells

    OpenAIRE

    Kim, Jin Joo; Ha, Ae Wha; Kim, Hee Sun; Kim, Woo Kyoung

    2011-01-01

    This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 µmol/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 µmol/L within 48 h. Inorganic sulfur significantly d...

  1. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer

    International Nuclear Information System (INIS)

    Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer. Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120). SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1+/+) or with control plasmid pcDNA4/GFP (MDA-MB-231+/-). MDA-MB-231SDF1+/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231+/-; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and

  2. Pepper seed extract suppresses invasion and migration of human breast cancer cells.

    Science.gov (United States)

    Kim, Hyeon-A; Kim, Min-Sook; Kim, Sang-Hyun; Kim, Yoo Kyeong

    2014-01-01

    This study was performed to determine the antimetastatic activities of chili pepper seed on human breast cancer cells. The water extract of chili pepper seeds was prepared and it contained a substantial amount of phenols (131.12 mg%) and no capsaicinoids. Pepper seed extract (PSE) suppressed the proliferation of MDA-MB-231 and MCF-7 cells at the concentration of 10, 25, and 50 μg/ml (MDA-MB-231: IC50 = 20.1 μg/ml, MCF-7: IC50 = 14.7 μg/ml). PSE increased the expression level of E-cadherin up to 1.2-fold of the control in MCF-7 cells. PSE also decreased the secretion of matrix metalloproteinase (MMP)-2 and MMP-9 in MDA-MB-231 and MCF-7 cells at the concentration of 25 and 50 μg/ml. PSE treatment significantly suppressed the invasion of MDA-MB-231 and MCF-7 cells in a dose-dependent manner. The motility of cancer cells was apparently retarded in the wound healing assay by the PSE treatment. Although our data collectively demonstrate that PSE inhibits invasion and migration of breast cancer cells, further study is needed to identify specific mechanisms and bioactive components contributing to antimetastatic effects of chili pepper seed. PMID:24341783

  3. Clinical trial of a minimally invasive operation for early breast cancer. One of the methods of day surgery

    International Nuclear Information System (INIS)

    Surgical management for primary breast cancer has become less invasive. We performed breast-conserving therapy (wide excision: Bp) and sentinel lymph node biopsy (SLNB) with local anesthesia as a clinical trial. We hypothesized that it is possible to manage early breast cancer by day surgery employing this method. Twenty-three patients with early breast cancer (maximum diameter: 2.0 cm, and no evidence of metastases of lymph nodes on preoperative image examinations) underwent this method. The treatment was completed without any complications in all cases. There were no disadvantages in the local anesthesia group compared with the general anesthesia group regarding oncological findings. In conclusion, this method is one of the options to manage early breast cancer in day surgery. (author)

  4. Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN

    Science.gov (United States)

    Menck, Kerstin; Scharf, Christian; Bleckmann, Annalen; Dyck, Lydia; Rost, Ulrike; Wenzel, Dirk; Dhople, Vishnu M.; Siam, Laila; Pukrop, Tobias; Binder, Claudia; Klemm, Florian

    2015-01-01

    Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologous and heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN. PMID:25503107

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-07

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

  6. A mouse stromal response to tumor invasion predicts prostate and breast cancer patient survival.

    Directory of Open Access Journals (Sweden)

    Marina Bacac

    Full Text Available Primary and metastatic tumor growth induces host tissue responses that are believed to support tumor progression. Understanding the molecular changes within the tumor microenvironment during tumor progression may therefore be relevant not only for discovering potential therapeutic targets, but also for identifying putative molecular signatures that may improve tumor classification and predict clinical outcome. To selectively address stromal gene expression changes during cancer progression, we performed cDNA microarray analysis of laser-microdissected stromal cells derived from prostate intraepithelial neoplasia (PIN and invasive cancer in a multistage model of prostate carcinogenesis. Human orthologs of genes identified in the stromal reaction to tumor progression in this mouse model were observed to be expressed in several human cancers, and to cluster prostate and breast cancer patients into groups with statistically different clinical outcomes. Univariate Cox analysis showed that overexpression of these genes is associated with shorter survival and recurrence-free periods. Taken together, our observations provide evidence that the expression signature of the stromal response to tumor invasion in a mouse tumor model can be used to probe human cancer, and to provide a powerful prognostic indicator for some of the most frequent human malignancies.

  7. Knockdown of OLA1, a regulator of oxidative stress response, inhibits motility and invasion of breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Jia-wei ZHANG; Valentina RUBIO; Shu ZHENG; Zheng-zheng SHI

    2009-01-01

    To explore the role of a novel Obg-like ATPase 1 (OLA1) in cancer metastasis, small interference RNA (siRNA) was used to knockdown the protein, and the cells were subjected to in vitro cell migration and invasion assays. Knockdown of OLA1 significantly inhibited cell migration and invasion in breast cancer cell line MDA-MB-231. The knockdown caused no changes in cell growth but affected ROS production. In wound-healing assays, decreased ROS in OLA1-knockdown cells were in situ asso-ciated with the cells' decreased motile morphology. Further, treatment of N-acetylcysteine, a general ROS scavenger, blunted the motility and invasiveness of MDA-MB-231 cells, similar to the effect of OLA1-knockdown. These results suggest that knock-down of OLA1 inhibits breast cancer cell migration and invasion through a mechanism that involves the modulation of intracel-lular ROS levels.

  8. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease.

    Science.gov (United States)

    Ahmed, Ahmed R H; Griffiths, Andrew B; Tilby, Michael T; Westley, Bruce R; May, Felicity E B

    2012-03-01

    The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination.

  9. Extra-nuclear signaling of progesterone receptor to breast cancer cell movement and invasion through the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Fu

    Full Text Available Progesterone plays a role in breast cancer development and progression but the effects on breast cancer cell movement or invasion have not been fully explored. In this study, we investigate the actions of natural progesterone and of the synthetic progestin medroxyprogesterone acetate (MPA on actin cytoskeleton remodeling and on breast cancer cell movement and invasion. In particular, we characterize the nongenomic signaling cascades implicated in these actions. T47-D breast cancer cells display enhanced horizontal migration and invasion of three-dimensional matrices in the presence of both progestins. Exposure to the hormones triggers a rapid remodeling of the actin cytoskeleton and the formation of membrane ruffles required for cell movement, which are dependent on the rapid phosphorylation of the actin-regulatory protein moesin. The extra-cellular small GTPase RhoA/Rho-associated kinase (ROCK-2 cascade plays central role in progesterone- and MPA-induced moesin activation, cell migration and invasion. In the presence of progesterone, progesterone receptor A (PRA interacts with the G protein G alpha(13, while MPA drives PR to interact with tyrosine kinase c-Src and to activate phosphatidylinositol-3 kinase, leading to the activation of RhoA/ROCK-2. In conclusion, our findings manifest that progesterone and MPA promote breast cancer cell movement via rapid actin cytoskeleton remodeling, which are mediated by moesin activation. These events are triggered by RhoA/ROCK-2 cascade through partially differing pathways by the two compounds. These results provide original mechanistic explanations for the effects of progestins on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers.

  10. MicroRNA-154 inhibits growth and invasion of breast cancer cells through targeting E2F5

    Science.gov (United States)

    Xu, Hui; Fei, Dan; Zong, Shan; Fan, Zhimin

    2016-01-01

    Accumulating evidence suggested that microRNA-154 (miR-154) might play important roles in the development of various cancer types. However, the role of miR-154 in breast cancer progression remains largely unknown. Here, miR-154 expression level was measured via quantitative real-time RT-PCR (qRT-PCR) in 36 pairs of human breast cancer tissues and adjacent normal breast tissues and in a panel of human breast cancer cell lines. Cell proliferation, cycle, migration, and invasion were assessed by CCK8 assay, flow cytometer assay, wound healing assay and transwell invasion assay, respectively. Luciferase reporter assay and Western blot was used to verify E2F transcription factor 5 protein (E2F5) as a novel target gene of miR-154. Our results showed that miR-154 was frequently downregulated in breast cancer tissues and cell lines. Overexpression of miR-154 in MCF-7 cells significantly inhibited cell proliferation, migration, and invasion, and increased cell arrest at G0/G1 stage in vitro. E2F5 was identified as a target of miR-154, and its expression was inversely correlated with miR-154 expression in clinical breast cancer tissues. In addition, downregulation of E2F5 in MCF7 cells had similar effect on cell proliferation, cycle, migration and invasion by miR-154 induced. These findings indicate that miR-154 acts as a tumor suppressor by targeting E2F5, suggesting miR-154 as a potential therapeutic target for the treatment of breast cancer. PMID:27398145

  11. Alternate estrogen receptors promote invasion of inflammatory breast cancer cells via non-genomic signaling.

    Directory of Open Access Journals (Sweden)

    Kazufumi Ohshiro

    Full Text Available Although Inflammatory Breast Cancer (IBC is a rare and an aggressive type of locally advanced breast cancer with a generally worst prognosis, little work has been done in identifying the status of non-genomic signaling in the invasiveness of IBC. The present study was performed to explore the status of non-genomic signaling as affected by various estrogenic and anti-estrogenic agents in IBC cell lines SUM149 and SUM190. We have identified the presence of estrogen receptor α (ERα variant, ERα36 in SUM149 and SUM190 cells. This variant as well as ERβ was present in a substantial concentration in IBC cells. The treatment with estradiol (E2, anti-estrogenic agents 4-hydroxytamoxifen and ICI 182780, ERβ specific ligand DPN and GPR30 agonist G1 led to a rapid activation of p-ERK1/2, suggesting the involvement of ERα36, ERβ and GPR30 in the non-genomic signaling pathway in these cells. We also found a substantial increase in the cell migration and invasiveness of SUM149 cells upon the treatment with these ligands. Both basal and ligand-induced migration and invasiveness of SUM149 cells were drastically reduced in the presence of MEK inhibitor U0126, implicating that the phosphorylation of ERK1/2 by MEK is involved in the observed motility and invasiveness of IBC cells. We also provide evidence for the upregulation of p-ERK1/2 through immunostaining in IBC patient samples. These findings suggest a role of non-genomic signaling through the activation of p-ERK1/2 in the hormonal dependence of IBC by a combination of estrogen receptors. These findings only explain the failure of traditional anti-estrogen therapies in ER-positive IBC which induces the non-genomic signaling, but also opens newer avenues for design of modified therapies targeting these estrogen receptors.

  12. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Dharmawardhane Suranganie F

    2005-04-01

    Full Text Available Abstract Background Inflammatory breast cancer (IBC is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. Results Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive properties to basal lamina, but SUM 149 showed a marked increase in adhesion to collagen I. In vitro haptotaxis assays demonstrate that SUM 149 was less invasive, while wound healing assays show a less in vitro migratory phenotype for SUM 149 cells relative to SUM 102 cells. We also demonstrate a role for Rho and E-cadherin in the unique invasive phenotype of IBC. Immunoblotting reveals higher E-cadherin and RhoA expression in the IBC cell line but similar RhoC expression. Rhodamine phalloidin staining demonstrates increased formation of actin stress fibers and larger focal adhesions in SUM 149 relative to the SUM 102 cell line. Conclusion The observed unique actin and cellular architecture as well as the invasive and adhesive responses to the extracellular matrix of SUM 149 IBC cells suggest that the preference of IBC cells for connective tissue, possibly a mediator important for the vasculogenic mimicry via tubulogenesis seen in IBC pathological specimens. Overexpression of E-cadherin and RhoA may contribute to passive dissemination of IBC by promoting cell-cell adhesion and actin cytoskeletal structures that maintain tissue integrity. Therefore, we believe that these findings indicate a passive metastatic mechanism by which IBC cells invade the circulatory system as tumor emboli rather than by active migratory mechanisms.

  13. Characterization of breast tissue composition and breast cancer risk assessment using non-invasive transillumination breast spectroscopy (TIBS)

    Science.gov (United States)

    Blackmore, Kristina M.; Weersink, Robert; Lilge, Lothar

    2005-09-01

    Tissue undergoing transformation into a state that is more favourable for tumor growth may present itself with different tissue optical properties and contain different amounts of the major tissue chromophores. Here, we decomposed transillumination spectra obtain in women from various risk levels of developing breast cancer.

  14. Small interfering RNA targeted to secretory clusterin blocks tumor growth, motility, and invasion in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhaohe Niu; Xinhui Li; Bin Hu; Rong Li; Ligang Wang; Lilin Wu; Xingang Wang

    2012-01-01

    Clusterin/apolipoprotein J (Clu) is a ubiquitously expressed secreted heterodimeric glycoprotein that is implicated in several physiological processes.It has been reported that the elevated level of secreted clusterin (sClu) protein is associated with poor survival in breast cancer patients and can induce metastasis in rodent models.In this study,we investigated the effects of sClu inhibition with small interfering RNAs (siRNAs) on cell motility,invasion,and growth in vitro and in vivo.MDA-MB-231 cells were transfected with pSuper-siRNA/sClu.Cell survival and proliferation were examined by 3-(4,5-dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and clonogenic survival assay.The results showed that sClu silencing significantly inhibited the proliferation of MDA-MB-231 cells.The invasion and migration ability were also dramatically decreased,which was detected by matrigel assays.TUNEL staining and caspase-3 activity assay demonstrated that sClu silencing also could increase the apoptosis rate of cells,resulting in the inhibition of cell growth.We also determined the effects of sClu silencing on tumor growth and metastatic progression in an orthotopic breast cancer model.The results showed that orthotopic primary tumors derived from MDA-MB-231/pSuper sClu siRNA cells grew significantly slower than tumors derived from parental MDA-MB-231 or MDA-MB-231/pSuper scramble siRNA cells,and metastasize less to the lungs.These data suggest that secretory clusterin plays a significant role in tumor growth and metastatic progression.Knocking-down sClu gene expression may provide a valuable method for breast cancer therapy.

  15. Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

    Science.gov (United States)

    2016-09-28

    Ductal Breast Carcinoma In Situ; Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Invasive Breast Carcinoma; Multicentric Breast Carcinoma; Multifocal Breast Carcinoma; Synchronous Bilateral Breast Carcinoma

  16. MicroRNA-106b targets FUT6 to promote cell migration, invasion, and proliferation in human breast cancer.

    Science.gov (United States)

    Li, Nana; Liu, Yuejian; Miao, Yuan; Zhao, Lifen; Zhou, Huimin; Jia, Li

    2016-09-01

    It is demonstrated that the maladjustment of microRNA (miRNA) plays significant roles in the occurrence and development of tumors. MicroRNA-106b-5p (miR-106b), a carcinogenic miRNA, is identified as a dysregulated miRNA in human breast cancer. In this article, the expression levels of miR-106b were discovered to be particularly higher in breast cancer tissues than that in the corresponding adjacent tissues. Accordingly, miR-106b was higher expressed in the breast cancer cell lines compared with that in the normal breast cell lines. Moreover, according to the data previously reported, increased expression of miR-106b was significantly associated with advanced clinical stages and poor prognosis in breast cancer. Fucosyltransferase 6 (FUT6), a member of the fucosyltransferase (FUT) family, was found to have a reduced expression in tissues or cells with higher level of miR-106b in breast cancer. Additionally, down-regulation of miR-106b increased the expression of FUT6 and resulted in an obvious decrease of cell migration, invasion, and proliferation in MDA-MB-231 cells. Furthermore, over-expressed FUT6 reversed the impacts of up-regulated miR-106b on cell migration, invasion, and proliferation in MCF-7 cells, indicating that FUT6 might be directly targeted by miR-106b and serve as therapeutic targets for breast cancer. In brief, our results strongly showed that the low expression of FUT6 regulated by miR-106b contributed to cell migration, invasion, and proliferation in human breast cancer. © 2016 IUBMB Life, 68(9):764-775, 2016. PMID:27519168

  17. 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 ...

  18. PTTG promotes invasion in human breast cancer cell line by upregulating EMMPRIN via FAK/Akt/mTOR signaling.

    Science.gov (United States)

    Gao, Hui; Zhong, Feng; Xie, Jing; Peng, Jianjun; Han, Zhiwu

    2016-01-01

    Pituitary tumor transforming gene (PTTG) is a novel oncogene that is expressed at higher level in most of the tumors. PTTG overexpression correlates with lymph node infiltration and a higher degree of tumor recurrence in breast cancer. However, the cellular functions and precise signals elicited by PTTG in breast cancer are not fully understood. Here, we established a breast cancer cell line which stably overexpressed PTTG. In vitro experiments showed that overexpression of PTTG in MCF-7 cells was associated with enhanced cell migration and invasion as well as EMT. Our results also demonstrated that PTTG overexpression correlated with elevated EMMPRIN level, which mediated the enhanced cell migration, invasion and EMT. Moreover, our findings suggested that PTTG enhances metastatic potential of breast cancer cells by inducing EMMPRIN through activating FAK/Akt/mTOR pathway. Our findings may lead to a better understanding of the biological effect of PTTG and provide mechanistic insights for developing potential therapeutic strategies for inhibiting the invasion and metastasis of breast cancer. PMID:27186413

  19. Long-term follow-up after treatment of invasive and in situ breast cancer : aspects on second breast cancers HRQOL and lymphoedema

    OpenAIRE

    Sackey, Helena

    2014-01-01

    Breast cancer is the most frequent cancer among Swedish women and in 2012, 8490 new inva- sive breast cancers were diagnosed. The incidence of in situ breast cancer has markedly in- creased since nationwide mammography screening was introduced in the late 1980s. The in- creasing figures of in situ breast cancer are predominantly attributable to an increased frequency of ductal carcinoma in situ (DCIS). In 2012, 1443 in situ breast cancers were diagnosed in Swe- den, which is approximately 15%...

  20. The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hyereen [Department of Medicine, Graduate School, University of Ulsan, Pungnap-2 dong, Songpa-gu, Seoul (Korea, Republic of); Ko, Jesang [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Jang, Sung-Wuk, E-mail: swjang@amc.seoul.kr [Department of Medicine, Graduate School, University of Ulsan, Pungnap-2 dong, Songpa-gu, Seoul (Korea, Republic of)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer We evaluated the effect of ANXA1 on promoting migration and invasion in MDA-MB-231 cells. Black-Right-Pointing-Pointer ANXA1 siRNA inhibits invasion and migration. Black-Right-Pointing-Pointer ANXA1 regulates MMP-9 expression and activity. Black-Right-Pointing-Pointer ANX-1 siRNA inhibits the activation of NF-{kappa}B in MDA-MB-231 cells. -- Abstract: Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. However, the regulatory mechanism of MMP-9 expression and its biological effects on breast cancer development remain obscure. In the current study, we examined the potential role of annexin A1 (ANXA1) in regulating migration and invasion in breast cancer cell lines. Both ANXA1 mRNA and protein are expressed in the highly invasive, hormone-insensitive human breast cancer cell lines MDA-MB-231 and SKBr3, but not in the hormone-responsive cell lines MCF-7 and T47D. Downregulation of ANXA1 expression with specific small interfering RNAs (ANXA1 siRNA) in MDA-MB-231 cells resulted in decreased cancer cell migration and invasion. Ablation of ANXA1 expression decreases the expression of MMP-9 at both the mRNA and protein levels and also reduces the proteolytic activity of MMP-9 in MDA-MB-231 cells. Moreover, silencing ANXA1 also decreases the transcriptional activity of MMP-9 by the suppression of nuclear factor kappa-B (NF-{kappa}B) activity. Collectively, these results indicate that ANXA1 functions as a positive regulator of MMP-9 expression and invasion of breast cancer cells through specific activation of the NF-{kappa}B signaling pathway.

  1. 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 ... the risk. Women who have family members with breast or ovarian cancer may wish to be tested ...

  2. Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines.

    Science.gov (United States)

    Gallardo, Marcela; Calaf, Gloria M

    2016-09-01

    Curcumin (diferuloyl methane) is an antioxidant that exerts antiproliferative and apoptotic effects and has anti-invasive and anti-metastatic properties. Evidence strongly implicates that epithelial-mesenchymal transition (EMT) is involved in malignant progression affecting genes such as Slug, AXL and Twist1. These genes are abnormally expressed in many tumors and favor metastasis. The purpose of this study was to determine the potential effect of curcumin on EMT, migration and invasion. Triple-positive and triple-negative breast cancer cell lines for estrogen receptor (ER), progesterone receptor (PgR) and HER/neu were used: i) MCF-10F, a normal immortalized breast epithelial cell line (negative), ii) Tumor2, a malignant and tumorigenic cell line (positive) derived from Alpha5 cell line injected into the immunologically depressed mice and transformed by 60/60 cGy doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation and estrogen, and iii) a commercially available MDA-MB‑231 (negative). The effect of curcumin (30 µM for 48 h) was evaluated on expression of EMT-related genes by RT-qPCR. Results showed that curcumin decreased E-cadherin, N-cadherin, β-catenin, Slug, AXL, Twist1, Vimentin and Fibronectin protein expression, independently of the positivity of the markers in the cell lines. Curcumin also decreased migration and invasive capabilities in comparison to their own controls. It can be concluded that curcumin influenced biochemical changes associated with EMT-related genes that seems to promote such transition and are at the core of several signaling pathways that mediate the transition. Thus, it can be suggested that curcumin is able to prevent or delay cancer progression through the interruption of this process.

  3. Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines.

    Science.gov (United States)

    Gallardo, Marcela; Calaf, Gloria M

    2016-09-01

    Curcumin (diferuloyl methane) is an antioxidant that exerts antiproliferative and apoptotic effects and has anti-invasive and anti-metastatic properties. Evidence strongly implicates that epithelial-mesenchymal transition (EMT) is involved in malignant progression affecting genes such as Slug, AXL and Twist1. These genes are abnormally expressed in many tumors and favor metastasis. The purpose of this study was to determine the potential effect of curcumin on EMT, migration and invasion. Triple-positive and triple-negative breast cancer cell lines for estrogen receptor (ER), progesterone receptor (PgR) and HER/neu were used: i) MCF-10F, a normal immortalized breast epithelial cell line (negative), ii) Tumor2, a malignant and tumorigenic cell line (positive) derived from Alpha5 cell line injected into the immunologically depressed mice and transformed by 60/60 cGy doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation and estrogen, and iii) a commercially available MDA-MB‑231 (negative). The effect of curcumin (30 µM for 48 h) was evaluated on expression of EMT-related genes by RT-qPCR. Results showed that curcumin decreased E-cadherin, N-cadherin, β-catenin, Slug, AXL, Twist1, Vimentin and Fibronectin protein expression, independently of the positivity of the markers in the cell lines. Curcumin also decreased migration and invasive capabilities in comparison to their own controls. It can be concluded that curcumin influenced biochemical changes associated with EMT-related genes that seems to promote such transition and are at the core of several signaling pathways that mediate the transition. Thus, it can be suggested that curcumin is able to prevent or delay cancer progression through the interruption of this process. PMID:27573203

  4. MicroRNA-200b Impacts Breast Cancer Cell Migration and Invasion by Regulating Ezrin-Radixin-Moesin.

    Science.gov (United States)

    Hong, Hong; Yu, Haizhong; Yuan, Jianfen; Guo, Chunyan; Cao, Hongyan; Li, Weibing; Xiao, Chunhong

    2016-01-01

    BACKGROUND Ezrin-radixin-moesin (ERM) plays an important role in multiple links of tumors. It also involved in breast cancer invasion and metastasis, and might be a potential biomarker of breast cancer. Another study suggested that ERM expression was regulated directly by miR-200c, and had a critical role in miR-200c suppressing cell migration. This study aimed to investigate the effect of miR-200b on ERM expression in a breast cancer cell line and its influence on invasion and metastasis ability in vitro. MATERIAL AND METHODS Breast cancer cell lines MCF-7 and MDA-MB-231 with different metastatic potentials were selected as a model. MiR-200b overexpression or inhibition was achieved by Lipofectamine™ 2000-mediated miRNA transfection. RT-PCR was used to test miR-200b level, while Western blot was selected to detect ERM protein expression. Wound healing assay and Transwell assay were performed to determine cell migration and invasion ability. RESULTS RT-PCR revealed that miR-200b level in MDA-MB-231 was obviously lower than that in MCF-7, while Western blot analysis showed that ERM expression was significantly higher. MiR-200b inhibition by transfection in MCF-7 markedly decreased miR-200b level, elevated ERM expression, and enhanced cell migration and invasion. MiR-200b overexpression in MDA-MB-231 obviously increased miR-200b level, reduced ERM expression, and weakened cell migration and invasion. CONCLUSIONS MiR-200b participates in breast cancer cell migration and invasion through regulating ERM in MCF-7 and MDA-MB-231. PMID:27276064

  5. miR-21 Might be Involved in Breast Cancer Promotion and Invasion Rather than in Initial Events of Breast Cancer Development.

    Science.gov (United States)

    Petrović, Nina

    2016-04-01

    Breast cancer (BC) is a heterogeneous disease that develops into a large number of varied phenotypes. One of the features used in its classification and therapy selection is invasiveness. MicroRNA-21 (miR-21) is considered to be an important element of BC invasiveness, and miR-21 levels are frequently increased in different tumor types compared with normal tissue, including the breast. Experimental and literature research has highlighted that miR-21 was always significantly elevated in every study that included invasive breast carcinomas compared with healthy breast tissue. The main goal of this research was to specify the predominant role of miR-21 in the different phases of BC pathogenesis, i.e. whether it was involved in the early (initiation), later (promotion), or late (propagation, progression) phases. Our second goal was to explain the roles of miR-21 targets in BC by an in silico approach and literature review, and to associate the importance of miR-21 with particular phases of BC pathogenesis through the action of its target genes. Analysis has shown that changes in miR-21 levels might be important for the later and/or late phases of breast cancerogenesis rather than for the initial early phases. Targets of miR-21 (TIMP3, PDCD4, PTEN, TPM1 and RECK) are also primarily involved in BC promotion and progression, especially invasion, angiogenesis and metastasis. miR-21 expression levels could perhaps be used in conjunction with the standard diagnostic parameters as an indicator of BC presence, and to indicate a phenotype likely to show early invasion/metastasis detection and poor prognosis. PMID:26891730

  6. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rajput, Ashish B. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Hu, Nianping [Cancer Research institute, Queen' s University, Kingston, ON K7L 3N6 (Canada); Varma, Sonal; Chen, Chien-Hung [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Ding, Keyue [NCIC Clinical Trials Group, Queen' s University, Kingston, ON K7L 3N6 (Canada); Park, Paul C. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Chapman, Judy-Anne W. [NCIC Clinical Trials Group, Queen' s University, Kingston, ON K7L 3N6 (Canada); SenGupta, Sandip K. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Madarnas, Yolanda [Cancer Research institute, Queen' s University, Kingston, ON K7L 3N6 (Canada); Department of Oncology, Cancer Center of Southeastern Ontario, Kingston, ON K7L 2V7 (Canada); Elliott, Bruce E.; Feilotter, Harriet E., E-mail: feilotth@kgh.kari.net [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada)

    2011-12-06

    Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)—the 70 gene signature MammaPrint{sup ®} and the five gene Molecular Grade Index (MGI{sup SM}). Our aim was to assess the immunohistochemical (IHC) expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM) estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS). Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02) in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei) was 79% compared to 85% in low expression tumors (<50% stained nuclei). On multivariate analysis, IHC expression of CENPA showed weak association with DFS (HR > 60.07; p = 0.06) within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker.

  7. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA in Human Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Bruce E. Elliott

    2011-12-01

    Full Text Available Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa—the 70 gene signature MammaPrint® and the five gene Molecular Grade Index (MGISM. Our aim was to assess the immunohistochemical (IHC expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS. Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02 in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei was 79% compared to 85% in low expression tumors ( 60.07; p = 0.06 within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Influences of neoadjuvant chemotherapy for serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Chuan-Xi Chen

    2016-01-01

    Objective:To explore and analyze the influences on neoadjuvant chemotherapy for serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer.Methods:Patients with advanced breast cancer who had been treated in our hospital from February 2010 to February 2014 were randomly selected as research objects. They were randomly divided into control group (conventional surgical treatment group) and observation group (neoadjuant chemotherapy group). There were 32 cases of each group. Then, the changes of the different periods of serum tumor markers, invasion and metastasis related indexes in pretherapy and post-treatment of patients with advanced breast cancer in the two groups were observed.Results:The postoperative serum tumor markers, invasion and metastasis related indexes in different periods of the observation group were all lower than those of the control group, and the postoperative evaluation indexes of the two groups had significant difference. Conclusions:Neoadjuvant chemotherapy has great influences on serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer and possesses high clinical application values.

  10. EZH2 knockdown suppresses the growth and invasion of human inflammatory breast cancer cells

    OpenAIRE

    Mu, Zhaomei; Li, Hua; Fernandez, Sandra V.; Alpaugh, Katherine R; Zhang, Rugang; Cristofanilli, Massimo

    2013-01-01

    Introduction Inflammatory breast cancer (IBC) is the most metastatic variant of breast cancer with the poorest survival in all types of breast cancer patients and presently therapeutic targets for IBC are very limited. Enhancer of zeste homolog 2 (EZH2) is frequently expressed in human IBC and its expression positively correlates with worse clinical outcome. However, the molecular basis for EZH2 promoting IBC has not been explored. Here, we investigated the functional role of EZH2 in IBC cell...

  11. FHL2 Antagonizes Id1-Promoted Proliferation and Invasive Capacity of Human MCF-7 Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Wei-dong Han; Zhi-qiang Wu; Ya-li Zhao; Yi-ling Si; Ming-zhou Guo; Xiao-bing Fu

    2010-01-01

    Objective:FHL2 was previously identified to be a novel interacting factor of Id family proteins.The aim of this study was to investigate,the effects of FHL2 on Id1-mediated transcriptional regulation activity and its oncogenic activity in human breast cancer cells.Methods:Cell transfection was performed by Superfect reagent.Id1 stably overexpressed MCF-7 cells was cloned by G418 screening.The protein level of Id1 was detected by western blot analysis.Dual relative luciferase assays were used to measure the effect of E47-mediated transcriptional activity in MCF-7 human breast cancer cells.MTT assay was used to measure cell proliferation.Transwell assay was used to measure the invasive capacity of MCF-7 cancer cells.Results:The basic helix-loop-helix(bHLH)factor E47-mediated transcription activity was markedly repressed by Id1 in MCF-7 cells.This Id1-mediated repression was effectively antagonized by FHL2 transduction.Overexpression of Id1 markedly promoted the proliferation rate and invasive capacity of MCF-7 cells; however,these effects induced by Id1 were significantly suppressed by overexpression of FHL2 in cells.Conclusion:FHL2 can inhibit the proliferation and invasiveness of human breast cancer cells by repressing the functional activity of Id1.These findings provide the basis for further investigating the functional roles of FHL2-Id1 signaling in the carcinogenesis and development of human breast cancer.

  12. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger;

    2009-01-01

    Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasiv...

  13. Biochanin A Modulates Cell Viability, Invasion, and Growth Promoting Signaling Pathways in HER-2-Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Vikas Sehdev

    2009-01-01

    Full Text Available Overexpression of HER-2 receptor is associated with poor prognosis and aggressive forms of breast cancer. Scientific literature indicates a preventive role of isoflavones in cancer. Since activation of HER-2 receptor initiates growth-promoting events in cancer cells, we studied the effect of biochanin A (an isoflavone on associated signaling events like receptor activation, downstream signaling, and invasive pathways. HER-2-positive SK-BR-3 breast cancer cells, MCF-10A normal breast epithelial cells, and NIH-3T3 normal fibroblast cells were treated with biochanin A (2–100 μM for 72 hours. Subsequently cell viability assay, western blotting and zymography were carried out. The data indicate that biochanin A inhibits cell viability, signaling pathways, and invasive enzyme expression and activity in SK-BR-3 cancer cells. Biochanin A did not inhibit MCF-10A and NIH-3T3 cell viability. Therefore, biochanin A could be a unique natural anticancer agent which can selectively target cancer cells and inhibit multiple signaling pathways in HER-2-positive breast cancer cells.

  14. Hormonal-receptor positive breast cancer: IL-6 augments invasion and lymph node metastasis via stimulating cathepsin B expression

    Directory of Open Access Journals (Sweden)

    Sherif A. Ibrahim

    2016-09-01

    Full Text Available Hormonal-receptor positive (HRP breast cancer patients with positive metastatic axillary lymph nodes are characterized by poor prognosis and increased mortality rate. The mechanisms by which cancer cells invade lymph nodes have not yet been fully explored. Several studies have shown that expression of IL-6 and the proteolytic enzyme cathepsin B (CTSB was associated with breast cancer poor prognosis. In the present study, the effect of different concentrations of recombinant human IL-6 on the invasiveness capacity of HRP breast cancer cell line MCF-7 was tested using an in vitro invasion chamber assay. The impact of IL-6 on expression and activity of CTSB was also investigated. IL-6 treatment promoted the invasiveness potential of MCF-7 cells in a dose-dependent manner. Furthermore, MCF-7 cells displayed elevated CTSB expression and activity associated with loss of E-cadherin and upregulation of vimentin protein levels upon IL-6 stimulation. To validate these results in vivo, the level of expression of IL-6 and CTSB in the carcinoma tissues of HRP-breast cancer patients with positive and negative axillary metastatic lymph nodes (pLNs and nLNs was assessed. Western blot and immunohistochemical staining data showed that expression of IL-6 and CTSB was higher in carcinoma tissues in HRP-breast cancer with pLNs than those with nLNs patients. ELISA results showed carcinoma tissues of HRP-breast cancer with pLNs exhibited significantly elevated IL-6 protein levels by approximately 2.8-fold compared with those with nLNs patients (P < 0.05. Interestingly, a significantly positive correlation between IL-6 and CTSB expression was detected in clinical samples of HRP-breast cancer patients with pLNs (r = 0.78, P < 0.01. Collectively, this study suggests that IL-6-induced CTSB may play a role in lymph node metastasis, and that may possess future therapeutic implications for HRP-breast cancer patients with pLNs. Further studies are necessary to fully

  15. Hormonal-receptor positive breast cancer: IL-6 augments invasion and lymph node metastasis via stimulating cathepsin B expression.

    Science.gov (United States)

    Ibrahim, Sherif A; El-Ghonaimy, Eslam A; Hassan, Hebatallah; Mahana, Noha; Mahmoud, Mahmoud Abdelbaky; El-Mamlouk, Tahani; El-Shinawi, Mohamed; Mohamed, Mona M

    2016-09-01

    Hormonal-receptor positive (HRP) breast cancer patients with positive metastatic axillary lymph nodes are characterized by poor prognosis and increased mortality rate. The mechanisms by which cancer cells invade lymph nodes have not yet been fully explored. Several studies have shown that expression of IL-6 and the proteolytic enzyme cathepsin B (CTSB) was associated with breast cancer poor prognosis. In the present study, the effect of different concentrations of recombinant human IL-6 on the invasiveness capacity of HRP breast cancer cell line MCF-7 was tested using an in vitro invasion chamber assay. The impact of IL-6 on expression and activity of CTSB was also investigated. IL-6 treatment promoted the invasiveness potential of MCF-7 cells in a dose-dependent manner. Furthermore, MCF-7 cells displayed elevated CTSB expression and activity associated with loss of E-cadherin and upregulation of vimentin protein levels upon IL-6 stimulation. To validate these results in vivo, the level of expression of IL-6 and CTSB in the carcinoma tissues of HRP-breast cancer patients with positive and negative axillary metastatic lymph nodes (pLNs and nLNs) was assessed. Western blot and immunohistochemical staining data showed that expression of IL-6 and CTSB was higher in carcinoma tissues in HRP-breast cancer with pLNs than those with nLNs patients. ELISA results showed carcinoma tissues of HRP-breast cancer with pLNs exhibited significantly elevated IL-6 protein levels by approximately 2.8-fold compared with those with nLNs patients (P positive correlation between IL-6 and CTSB expression was detected in clinical samples of HRP-breast cancer patients with pLNs (r = 0.78, P node metastasis, and that may possess future therapeutic implications for HRP-breast cancer patients with pLNs. Further studies are necessary to fully identify IL-6/CTSB axis in different molecular subtypes of breast cancer. PMID:27482469

  16. ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression

    DEFF Research Database (Denmark)

    Rafn, Bo; Nielsen, Christian Thomas Friberg; Andersen, Sofie Hagel;

    2012-01-01

    signaling network activates the transcription of cathepsin B gene (CTSB) via myeloid zinc finger-1 transcription factor that binds to an ErbB2-responsive enhancer element in the first intron of CTSB. This work provides a model system for ErbB2-induced breast cancer cell invasiveness, reveals a signaling......Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive primary human breast cancer and function...... as effectors of ErbB2-induced invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as essential mediators of ErbB2-induced cysteine cathepsin expression and breast cancer cell invasiveness. The identified...

  17. The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis

    OpenAIRE

    Xu, Kun; Tian, Xuejun; Oh, Sun Y.; Movassaghi, Mohammad; Naber, Stephen P.; Kuperwasser, Charlotte; Buchsbaum, Rachel J

    2016-01-01

    Background The tumor microenvironment has complex effects in cancer pathophysiology that are not fully understood. Most cancer therapies are directed against malignant cells specifically, leaving pro-malignant signals from the microenvironment unaddressed. Defining specific mechanisms by which the tumor microenvironment contributes to breast cancer metastasis may lead to new therapeutic approaches against advanced breast cancer. Methods We use a novel method for manipulating three-dimensional...

  18. Effect of aluminium on migratory and invasive properties of MCF-7 human breast cancer cells in culture.

    Science.gov (United States)

    Darbre, Philippa D; Bakir, Ayse; Iskakova, Elzira

    2013-11-01

    Aluminium (Al) has been measured in human breast tissue, nipple aspirate fluid and breast cyst fluid, and recent studies have shown that at tissue concentrations, aluminium can induce DNA damage and suspension growth in human breast epithelial cells. This paper demonstrates for the first time that exposure to aluminium can also increase migratory and invasive properties of MCF-7 human breast cancer cells. Long-term (32 weeks) but not short-term (1 week) exposure of MCF-7 cells to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate increased motility of the cells as measured by live cell imaging (cumulative length moved by individual cells), by a wound healing assay and by migration in real time through 8 μm pores of a membrane using xCELLigence technology. Long-term exposure (37 weeks) to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate also increased the ability of MCF-7 cells to invade through a matrigel layer as measured in real time using the xCELLigence system. Although molecular mechanisms remain to be characterized, the ability of aluminium salts to increase migratory and invasive properties of MCF-7 cells suggests that the presence of aluminium in the human breast could influence metastatic processes. This is important because mortality from breast cancer arises mainly from tumour spread rather than from the presence of a primary tumour in the breast.

  19. 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 ...

  20. The nude mouse as an in vivo model for human breast cancer invasion and metastasis

    DEFF Research Database (Denmark)

    Brünner, N; Boysen, B; Rømer, J;

    1993-01-01

    Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains...

  1. Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue – a GC-TOFMS based metabolomics study

    Directory of Open Access Journals (Sweden)

    Budczies Jan

    2012-07-01

    Full Text Available Abstract Background Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far. Results A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79% were significantly changed between cancer and normal tissues (p80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%. Conclusions For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.

  2. 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

  3. Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation.

    Science.gov (United States)

    Kim, Hyun Ji; Kang, Gyeoung Jin; Kim, Eun Ji; Park, Mi Kyung; Byun, Hyun Jung; Nam, Seungyoon; Lee, Ho; Lee, Chang Hoon

    2016-09-01

    Sphingosylphosphorylcholine (SPC) participates in several cellular processes including metastasis. SPC induces keratin reorganization and regulates the viscoelasticity of metastatic cancer cells including PANC-1 cancer cells leading to enhanced migration and invasion. The role of SPC and the relevant mechanism in invasion of breast cell are as yet unknown. SPC dose-dependently induces invasion of breast cancer cells or breast immortalized cells. Reverse transcription polymerase chain reaction and Western blot analyses of MCF10A and ZR-75-1 cells indicated that SPC induces expression and secretion of matrix metalloproteinase-3 (MMP3). From online KMPLOT, relapse free survival is high in patients having low MMP3 expressed basal breast cancer (n=581, p=0.032). UK370106 (MMP3 inhibitor) or gene silencing of MMP3 markedly inhibited the SPC-induced invasion of MCF10A cells. An extracellular signal-regulated kinase (ERK) inhibitor, PD98059, significantly suppressed the secretion and the gelatinolytic activity of MMP3, and invasion in MCF10A cells. Over-expression of ERK1 and ERK2 promoted both the expression and secretion of MMP3. In contrast, gene silencing of ERK1 and ERK2 attenuated the secretion of MMP3 in MCF10A cells. The effects of SPC-induced MMP3 secretion on β-catenin and TCF/lymphoid enhancer factor (LEF) promoter activity were examined since MMP3 indirectly activates canonical Wnt signaling. SPC induced translocation of β-catenin to nucleus and increased TCF/LEF promoter activity. These events were suppressed by UK370106 or PD98059. Wnt inhibitor, FH535 inhibited SPC-induced MMP3 secretion and invasion. Taken together, these results suggest that SPC induces MMP3 expression and secretion via ERK leading to Wnt activation. PMID:27216977

  4. Down-Regulation of CXCR4 Expression by siRNA Inhibits Invasive Ability of Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate the efficiency of gene silencing by CXCR4-siRNAs (small interfering RNA), and to examine the invasive ability and the expression of other metastatic-associated genes in siRNA-treated breast cancer cells.METHODS Three siRNAs were designed and cloned into the pSilenc TM 3.1-H1 neo vector. The reconstructed plasmids were purified and transfected into the T47D breast cancer cell line, which highly expressed CXCR4.The amount of CXCR4 expression in the transfected cells was measured by flow cytometry and Real-time PCR. Cell invasive ability was evaluated using 24-well Matrigel invasion chambers. In addition, the expression of other metastatic-associated genes, such as E-cad, IGFBP-5, FN and MMP-2, was assessed by Real-time PCR.RESULTS The suppression rates of CXCR4 mRNA expression reached 95.7%, 85.9% and 98.3%compared with control-siRNA cells in the 3 CXCR4-siRNA T47D cells respectively. FCM assays for CXCR4 protein expression showed a similar inhibitory effect. The invasion indexes of these CXCR4-siRNA cells were 0.037, 0.290 and 0.188 respectively compared with control-siRNA cells. After treatment of the cells with CXCR4-siRNA, the expression of E-cad showed an upward tendency and that of IGFBP-5 had a downward trend, while alteration in expression of FN and MMP2 varied without a consistant effect.CONCLUSION CXCR4 plays an important role in modulating migration of human breast cancer cells. Small interfering RNA can significantly silence the CXCR4 gene in the human T47D breast cancer cell line. The results of this study strengthen the need for further research on novel gene therapy against breast cancer metastasis.

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

    Science.gov (United States)

    Akl, Mohamed R; Ayoub, Nehad M; Mohyeldin, Mohamed M; Busnena, Belnaser A; Foudah, Ahmed I; Liu, Yong-Yu; Sayed, Khalid A Ei

    2014-01-01

    Dysregulation of the Hepatocyte growth factor (HGF)/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT), angiogenesis, invasion, and metastasis. (-)-Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (-)-oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (-)-oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (-)-oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (-)-oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (-)-oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (-)-oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity. PMID:24849787

  6. FHL2 inhibits the Id3-promoted proliferation and invasive growth of human MCF-7 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi-hong; WU Zhi-qiang; ZHAO Ya-li; SI Yi-ling; GUO Ming-zhou; HAN Wei-dong

    2012-01-01

    Background Id3 plays a key role in the progression of breast cancer.Previously,four and a half LIM protein (FHL2) was identified as a repressor of Id family proteins by interacting with them.This study aimed to investigate the effects of FHL2 on the transcriptional regulation and oncogenic activities of Id3 in human breast cancer cells.Methods Cell transfection was performed with SuperFect reagent.Stable transfectants that overexpressed Id3 were obtained by selection on G418.The level of Id3 protein was determined by Western blotting analysis.Dual luciferase assays were used to measure the effect of Id3 and FHL2 on E47-mediated transcriptional activity in MCF-7 human breast cancer cells.The MTT assay was used to measure cell proliferation.The transwell assay was used to measure the invasive capacity of MCF-7 cancer cells.Results Id3 markedly repressed transcription mediated by the basic helix-loop-helix (bHLH) factor E47 in MCF-7 cells.This Id3-mediated repression was effectively antagonized by FHL2.Overexpression of Id3 markedly promoted the proliferation and invasive capacity of MCF-7 cells; however,these effects were significantly suppressed by the overexpression of FHL2.Conclusions FHL2 can inhibit the proliferation and invasive growth of human breast cancer cells by repressing the functional activity of Id3.The functional roles of FHL2-1d3 signaling in the development of human breast cancer need further research.

  7. Modeling invasive breast cancer: growth factors propel progression of HER2-positive premalignant lesions.

    Science.gov (United States)

    Pradeep, C-R; Zeisel, A; Köstler, W J; Lauriola, M; Jacob-Hirsch, J; Haibe-Kains, B; Amariglio, N; Ben-Chetrit, N; Emde, A; Solomonov, I; Neufeld, G; Piccart, M; Sagi, I; Sotiriou, C; Rechavi, G; Domany, E; Desmedt, C; Yarden, Y

    2012-08-01

    The HER2/neu oncogene encodes a receptor-like tyrosine kinase whose overexpression in breast cancer predicts poor prognosis and resistance to conventional therapies. However, the mechanisms underlying aggressiveness of HER2 (human epidermal growth factor receptor 2)-overexpressing tumors remain incompletely understood. Because it assists epidermal growth factor (EGF) and neuregulin receptors, we overexpressed HER2 in MCF10A mammary cells and applied growth factors. HER2-overexpressing cells grown in extracellular matrix formed filled spheroids, which protruded outgrowths upon growth factor stimulation. Our transcriptome analyses imply a two-hit model for invasive growth: HER2-induced proliferation and evasion from anoikis generate filled structures, which are morphologically and transcriptionally analogous to preinvasive patients' lesions. In the second hit, EGF escalates signaling and transcriptional responses leading to invasive growth. Consistent with clinical relevance, a gene expression signature based on the HER2/EGF-activated transcriptional program can predict poorer prognosis of a subgroup of HER2-overexpressing patients. In conclusion, the integration of a three-dimensional cellular model and clinical data attributes progression of HER2-overexpressing lesions to EGF-like growth factors acting in the context of the tumor's microenvironment.

  8. Rb suppresses collective invasion, circulation and metastasis of breast cancer cells in CD44-dependent manner.

    Directory of Open Access Journals (Sweden)

    Kui-Jin Kim

    Full Text Available Basal-like breast carcinomas (BLCs present with extratumoral lymphovascular invasion, are highly metastatic, presumably through a hematogenous route, have augmented expression of CD44 oncoprotein and relatively low levels of retinoblastoma (Rb tumor suppressor. However, the causal relation among these features is not clear. Here, we show that Rb acts as a key suppressor of multiple stages of metastatic progression. Firstly, Rb suppresses collective cell migration (CCM and CD44-dependent formation of F-actin positive protrusions in vitro and cell-cluster based lymphovascular invasion in vivo. Secondly, Rb inhibits the release of single cancer cells and cell clusters into the hematogenous circulation and subsequent metastatic growth in lungs. Finally, CD44 expression is required for collective motility and all subsequent stages of metastatic progression initiated by loss of Rb function. Altogether, our results suggest that Rb/CD44 pathway is a crucial regulator of CCM and metastatic progression of BLCs and a promising target for anti-BLCs therapy.

  9. Peritumoral apparent diffusion coefficients for prediction of lymphovascular invasion in clinically node-negative invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Naoko; Mugikura, Shunji; Takasawa, Chiaki; Shimauchi, Akiko; Ota, Hideki; Takase, Kei; Takahashi, Shoki [Tohoku University Graduate School of Medicine, Department of Diagnostic Radiology, Sendai (Japan); Miyashita, Minoru; Ishida, Takanori [Tohoku University Graduate School of Medicine, Department of Surgical Oncology, Sendai (Japan); Kasajima, Atsuko [Tohoku University Graduate School of Medicine, Department of Pathology, Sendai (Japan); Kodama, Tetsuya [Tohoku University Graduate School of Medicine, Department of Biomedical Engineering, Sendai (Japan)

    2016-02-15

    To evaluate whether visual assessment of T2-weighted imaging (T2WI) or an apparent diffusion coefficient (ADC) could predict lymphovascular invasion (LVI) status in cases with clinically node-negative invasive breast cancer. One hundred and thirty-six patients with 136 lesions underwent MRI. Visual assessment of T2WI, tumour-ADC, peritumoral maximum-ADC and the peritumour-tumour ADC ratio (the ratio between them) were compared with LVI status of surgical specimens. No significant relationship was found between LVI and T2WI. Tumour-ADC was significantly lower in the LVI-positive (n = 77, 896 ± 148 x 10{sup -6} mm{sup 2}/s) than the LVI-negative group (n = 59, 1002 ± 163 x 10{sup -6} mm{sup 2}/s; p < 0.0001). Peritumoral maximum-ADC was significantly higher in the LVI-positive (1805 ± 355 x 10{sup -6} mm{sup 2}/s) than the LVI-negative group (1625 ± 346 x 10{sup -6} mm{sup 2}/s; p = 0.0003). Peritumour-tumour ADC ratio was significantly higher in the LVI-positive (2.05 ± 0.46) than the LVI-negative group (1.65 ± 0.40; p < 0.0001). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) of the peritumour-tumour ADC ratio was the highest (0.81). The most effective threshold for the peritumour-tumour ADC ratio was 1.84, and the sensitivity, specificity, positive predictive value and negative predictive value were 77 % (59/77), 76 % (45/59), 81 % (59/73) and 71 % (45/63), respectively. We suggest that the peritumour-tumour ADC ratio can assist in predicting LVI status on preoperative imaging. (orig.)

  10. EFFECTS OF ESTETROL ON MIGRATION AND INVASION IN T47-D BREAST CANCER CELLS THROUGH THE ACTIN CYTOSKELETON

    Directory of Open Access Journals (Sweden)

    Maria Silvia eGiretti

    2014-05-01

    Full Text Available Estetrol (E4 is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17β-estradiol (E2 on T47-D estrogen receptor (ER positive breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, redistribution of actin fibers towards the cell membrane was observed. However, when E4 was added to E2, a inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin (ERM family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr558, which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of ERα. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring estrogen receptor modulator in the breast.

  11. Effects of Estetrol on Migration and Invasion in T47-D Breast Cancer Cells through the Actin Cytoskeleton.

    Science.gov (United States)

    Giretti, Maria Silvia; Montt Guevara, Maria Magdalena; Cecchi, Elena; Mannella, Paolo; Palla, Giulia; Spina, Stefania; Bernacchi, Guja; Di Bello, Silvia; Genazzani, Andrea Riccardo; Genazzani, Alessandro D; Simoncini, Tommaso

    2014-01-01

    Estetrol (E4) is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor (ER) modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17β-estradiol (E2) on T47-D ER+ breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, re-distribution of actin fibers toward the cell membrane was observed. However, when E4 was added to E2, an inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr(558), which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of estrogen receptor-α. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring ER modulator in the breast. PMID:24904530

  12. Targeting Notch1 inhibits invasion and angiogenesis of human breast cancer cells via inhibition Nuclear Factor-κB signaling.

    Science.gov (United States)

    Liu, Yuan; Su, Chuanfu; Shan, Yuqing; Yang, Shouxiang; Ma, Guifeng

    2016-01-01

    Notch-1, a type-1 transmembrane protein, plays critical roles in the pathogenesis and progression of human malignancies, including breast cancer; however, the precise mechanism by which Notch-1 causes tumor cell invasion and angiogenesis remain unclear. Nuclear factor-κB (NF-κB), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are critically involved in the processes of tumor cell invasion and metastasis, we investigated whether targeting Notch-1 could be mechanistically associated with the down-regulation of NF-κB, IL-8, VEGF, and MMP-9, resulting in the inhibition of invasion and angiogenesis of breast cancer cells. Our data showed that down-regulation of Notch-1 leads to the inactivation of NF-κB activity and inhibits the expression of its target genes, such as IL-8, VEGF and MMP-9. We also found that down-regulation of Notch-1 decreased cell invasion, and vice versa Consistent with these results, we also found that the down-regulation of Notch-1 not only decreased MMP-9 mRNA and its protein expression but also inhibited MMP-9 active form. Moreover, conditioned medium from Notch-1 siRNA-transfected breast cancer cells showed reduced levels of IL-8 and VEGF and, in turn, inhibited the tube formation of HUVECs, suggesting that down-regulation of Notch-1 leads to the inhibition of angiogenesis. Furthermore, conditioned medium from Notch-1 cDNA-transfected breast cancer cells showed increased levels of IL-8 and VEGF and, in turn, promoted the tube formation of HUVECs, suggesting that Notch-1 overexpression leads to the promotion of angiogenesis.We therefore concluded that down-regulation of Notch-1 leads to the inactivation NF-κB and its target genes (IL-8, MMP-9 and VEGF), resulting in the inhibition of invasion and angiogenesis.

  13. Phosphorus Magnetic Resonance Spectroscopy in Breast Cancer

    NARCIS (Netherlands)

    van der Kemp, W.J.M.

    2014-01-01

    At present, the risk of a woman developing invasive breast cancer during her life is about 1 in 8. This makes breast cancer the most prevalent type of cancer in women worldwide. As the risk of dying from breast cancer for a woman is about 1 in 36, early breast cancer detection and effective treatmen

  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. 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.

  16. Evaluation of the potential for lymph node metastasis using CRP 1846C>T genetic polymorphism in invasive breast cancer.

    Science.gov (United States)

    Terata, Kaori; Motoyama, Satoru; Kamata, Shuichi; Hinai, Yudai; Miura, Masatomo; Sato, Yusuke; Yoshino, Kei; Ito, Aki; Imai, Kazuhiro; Saito, Hajime; Minamiya, Yoshihiro

    2014-06-01

    Lymph node status is a key indicator of the best approach to treatment of invasive breast cancer. However, the accuracy with which lymph node metastasis is diagnosed is not currently satisfactory. New and more reliable methods that enable one to know who has a greater potential for lymph node metastasis would be highly desirable. We previously reported that lymph node involvement in esophageal and lung cancer may have a genetic component: C-reactive protein (CRP) 1846C>T genetic polymorphism. Here we examined the diagnostic value of CRP 1846C>T polymorphism for assessing the risk of lymph node metastasis in cases of invasive breast cancer. The study participants were 185 women with invasive breast cancer who underwent curative surgery with lymph node dissection. Using DNA from blood samples and polymerase chain reaction-restriction fragment length polymorphism, the utility of CRP genetic 1846C>T polymorphism (rs1205) for assessing the risk of lymph node metastasis was evaluated. Fifty-two (28 %) patients had lymph node metastasis. After the patients were divided into two groups based on their CRP 1846 genotypes (C/C+C/T and T/T), the clinical characteristics did not differ between the groups, but there was a significantly greater incidence of lymph node metastasis among patients in the T/T group. Moreover, the odds ratio for lymph node involvement in patients carrying the 1846 T/T genotype was more than 2.2 in multivariate logistic regression models. CRP genetic polymorphism may be a novel predictor of the risk of lymph node metastasis in invasive breast cancer.

  17. Genome and transcriptome delineation of two major oncogenic pathways governing invasive ductal breast cancer development

    Science.gov (United States)

    Aswad, Luay; Yenamandra, Surya Pavan; Ow, Ghim Siong; Grinchuk, Oleg; Ivshina, Anna V.; Kuznetsov, Vladimir A.

    2015-01-01

    Invasive ductal carcinoma (IDC) is a major histo-morphologic type of breast cancer. Histological grading (HG) of IDC is widely adopted by oncologists as a prognostic factor. However, HG evaluation is highly subjective with only 50%–85% inter-observer agreements. Specifically, the subjectivity in the assignment of the intermediate grade (histologic grade 2, HG2) breast cancers (comprising ~50% of IDC cases) results in uncertain disease outcome prediction and sub-optimal systemic therapy. Despite several attempts to identify the mechanisms underlying the HG classification, their molecular bases are poorly understood. We performed integrative bioinformatics analysis of TCGA and several other cohorts (total 1246 patients). We identified a 22-gene tumor aggressiveness grading classifier (22g-TAG) that reflects global bifurcation in the IDC transcriptomes and reclassified patients with HG2 tumors into two genetically and clinically distinct subclasses: histological grade 1-like (HG1-like) and histological grade 3-like (HG3-like). The expression profiles and clinical outcomes of these subclasses were similar to the HG1 and HG3 tumors, respectively. We further reclassified IDC into low genetic grade (LGG = HG1+HG1-like) and high genetic grade (HGG = HG3-like+HG3) subclasses. For the HG1-like and HG3-like IDCs we found subclass-specific DNA alterations, somatic mutations, oncogenic pathways, cell cycle/mitosis and stem cell-like expression signatures that discriminate between these tumors. We found similar molecular patterns in the LGG and HGG tumor classes respectively. Our results suggest the existence of two genetically-predefined IDC classes, LGG and HGG, driven by distinct oncogenic pathways. They provide novel prognostic and therapeutic biomarkers and could open unique opportunities for personalized systemic therapies of IDC patients. PMID:26474389

  18. Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA.

    Directory of Open Access Journals (Sweden)

    Makio Saeki

    Full Text Available Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.

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

    Directory of Open Access Journals (Sweden)

    L. Zhao

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-12

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

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

    International Nuclear Information System (INIS)

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

  2. 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 ...

  3. 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 ...

  4. Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells.

    Science.gov (United States)

    Kattan, Zilal; Minig, Vanessa; Leroy, Pierre; Dauça, Michel; Becuwe, Philippe

    2008-03-01

    Manganese superoxide dismutase (MnSOD) is known to play a role in cancer. MnSOD exerts a tumor suppressive effect in estrogen-dependent human breast cancer cells. In the present study we investigated the in vitro role of MnSOD in the growth of some aggressive and highly metastatic estrogen-independent breast cancer cells, i.e., MDA-MB231 and SKBR3 cells. We show that estrogen-independent cells expressed a significantly higher basal MnSOD level compared to estrogen-dependent human breast cancer cell lines (MCF-7 and T47D). For MDA-MB231 cells, the high-MnSOD level was accompanied by an overproduction of intracellular hydrogen peroxide (H2O2) and by a low expression of the major H2O2-detoxifying enzymes, catalase, and peroxiredoxin 3, compared to MCF-7 cells. Suppression of MnSOD expression by antisense RNA was associated with a decrease of H2O2 content and caused a stimulation of growth with a reduced cell doubling time but induced a decrease of colony formation. Furthermore, treatment of MDA-MB231 cells with H2O2 scavengers markedly reduced tumor cell growth and colony formation. In addition, MnSOD suppression or treatment with H2O2 scavengers reduced the invasive properties of MDA-MB231 cells up to 43%, with a concomitant decrease of metalloproteinase-9 activity. We conclude that MnSOD plays a role in regulating tumor cell growth and invasive properties of estrogen-independent metastatic breast cancer cells. These action are mediated by MnSOD-dependent H2O2 production. In addition, these results suggest that MnSOD up-regulation may be one mechanism that contributes to the development of metastatic breast cancers.

  5. Mammographic casting-type calcification associated with small screen-detected invasive breast cancers: is this a reliable prognostic indicator?

    International Nuclear Information System (INIS)

    AIM: The aim of the present study was to establish whether mammographic casting-type calcification associated with small screen-detected invasive breast cancers is a reliable prognostic indicator. METHODS AND MATERIALS: We retrospectively identified 50 consecutive women diagnosed with an invasive cancer less than 15 mm who showed associated casting calcification on their screening mammograms. Controls were identified that showed no microcalcification and were matched for tumour size, histological type and lymph node status. A minimum of 5 years follow-up was obtained, noting recurrence and outcome. Conditional and unconditional logistic regression, depending on the outcome variable, were used to analyse the data, taking the matched design into account in both cases. Where small numbers prohibited the use of logistic regression, Fisher's exact test was used. RESULTS: Five deaths from breast cancer occurred out of the 50 cases, of which three were lymph node positive, two were lymph node negative and none were grade 3. None of the 78 control cases died from breast cancer. The difference in breast cancer death rates was significant by Fisher's exact test (p=0.02). Risk of recurrence was also significantly increased in the casting cases (OR=3.55, 95% CI 1.02-12.33, p=0.046). CONCLUSION: Although the overall outcome for small screen-detected breast cancers is good, our study suggests that casting calcification is a poorer prognostic factor. The advantage of a mammographic feature as an independent prognostic indicator lies in early identification of high-risk patients, allowing optimization of management

  6. Heat shock protein 90β stabilizes focal adhesion kinase and enhances cell migration and invasion in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Xiangyang [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi 330006 (China); State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China); Wang, Yao [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Liu, Chengmei [State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China); Lu, Quqin [Department of Biostatistics and Epidemiology, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006 (China); Liu, Tao [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Chen, Guoan [Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006 (China); Rao, Hai [Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Luo, Shiwen, E-mail: shiwenluo@ncu.edu.cn [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China)

    2014-08-01

    Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may promote cell spreading, motility, invasion and survival in malignancy. Elevated expression and activity of FAK frequently correlate with tumor cell metastasis and poor prognosis in breast cancer. However, the mechanisms by which the turnover of FAK is regulated remain elusive. Here we report that heat shock protein 90β (HSP90β) interacts with FAK and the middle domain (amino acids 233–620) of HSP90β is mainly responsible for this interaction. Furthermore, we found that HSP90β regulates FAK stability since HSP90β inhibitor 17-AAG triggers FAK ubiquitylation and subsequent proteasome-dependent degradation. Moreover, disrupted FAK-HSP90β interaction induced by 17-AAG contributes to attenuation of tumor cell growth, migration, and invasion. Together, our results reveal how HSP90β regulates FAK stability and identifies a potential therapeutic strategy to breast cancer. - Highlights: • HSP90β protects FAK from degradation by the ubiquitin-proteasome pathway. • Inhibition of HSP90β or FAK attenuates tumorigenesis of breast cancer cells. • Genetic repression of HSP90β or FAK inhibits tumor cell migration and proliferation. • Inhibition of HSP90β or FAK interferes cell invasion and cytoskeleton.

  7. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells.

    Science.gov (United States)

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-01-01

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the "Alba" variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy. PMID:27498973

  8. 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 ...

  9. Vascular endothelial growth inhibitor affects the invasion, apoptosis and vascularisation in breast cancer cell line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    Gao Yinguang; Ge Zhicheng; Zhang Zhongtao; Bai Zhigang; Ma Xuemei; Wang Yu

    2014-01-01

    Background Breast cancer is one of the most common malignant female diseases worldwide.It is a significant threat to every woman's health.Vascular endothelial growth inhibitor (VEGI) is known to be abundant in endothelial cells.According to previous literature,overexpression of VEGI has been shown to inhibit tumor neovascularisation and progression in cellular and animal models,but there has been limited research on the significance of VEGI in the breast cancer.Methods In our study,cell lines MDA-MB-231 were first constructed in which VEGI mediated by lentivirus over-expressed.The effects of VEGI over-expression on MDA-MB-231 cells were investigated both in vitro and in vivo.The expression of VEGI in the MDA-MB-231 cells after infection of lentivirus was analyzed using real-time PCR and Western blotting.The effect of the biological characteristics of MDA-MB-231 cells was assessed by growth,invasion,adhesion,and migration assay with subcutaneous tumor-bearing nude mice models.Then the growth curves of the subcutaneous tumors were studied.Expressions of VEGI,CD31 and CD34 in the tumors were analyzed by immunohistochemistry and apoptosis was detected by flow cytometry and immunohistochemistry.Results Infection of MDA-MB-231 cells within the lentivirus resulted in approximately a 1 000-fold increase in the expression of VEGI.As can be seen in the invasion,adhesion and migration assay,the over-expression of VEGI can inhibit the ability of MDA-MB-231 cells during migration,adhesion and invasion.The volume of the subcutaneous tumor in the over-expression group was distinctly and significantly less than that of the control groups.Immunohistochemistry analysis of the tumor biopsies cleady showed the expression of VEGI in the over-expression group increased while CD31 and CD34 decreased significantly.In vitro and in vivo,the early apoptosis rate and the apoptosis index were increased within the VEGI over-expression group as compared with the control group.Conclusions Taken

  10. The effect of a DNA repair gene on cellular invasiveness: XRCC3 over-expression in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Veronica L Martinez-Marignac

    Full Text Available Over-expression of DNA repair genes has been associated with resistance to radiation and DNA-damage induced by chemotherapeutic agents such as cisplatin. More recently, based on the analysis of genome expression profiling, it was proposed that over-expression of DNA repair genes enhances the invasive behaviour of tumour cells. In this study we present experimental evidence utilizing functional assays to test this hypothesis. We assessed the effect of the DNA repair proteins known as X-ray complementing protein 3 (XRCC3 and RAD51, to the invasive behavior of the MCF-7 luminal epithelial-like and BT20 basal-like triple negative human breast cancer cell lines. We report that stable or transient over-expression of XRCC3 but not RAD51 increased invasiveness in both cell lines in vitro. Moreover, XRCC3 over-expressing MCF-7 cells also showed a higher tumorigenesis in vivo and this phenotype was associated with increased activity of the metalloproteinase MMP-9 and the expression of known modulators of cell-cell adhesion and metastasis such as CD44, ID-1, DDR1 and TFF1. Our results suggest that in addition to its' role in facilitating repair of DNA damage, XRCC3 affects invasiveness of breast cancer cell lines and the expression of genes associated with cell adhesion and invasion.

  11. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  12. Mammographic features of screening detected pT1 (a–b) invasive breast cancer using BI-RADS lexicon

    International Nuclear Information System (INIS)

    Aim: To describe mammographic features in screening detected invasive breast cancer less than or equal to 10 mm using Breast Imaging Reporting and Data System lexicon in full-field digital mammography. Patients and methods: A retrospective analysis of 123 pT1 (a–b) invasive breast cancers in women aged 50–69 years from our screening program. Radiologic patterns were: masses, calcifications, distortions, asymmetries and mixed. Masses: shape, margins and density, and calcifications: morphology, number of flecks and size of the cluster were taken into account, following Breast Imaging Reporting and Data System terminology. Results: We found 61 masses (49.6%), 8 masses with calcifications (6.5%), 30 groups of calcifications (24.4%), 19 architectural distortions (15.4%), 1 architectural distortion with calcifications (0.8%), 4 asymmetries (3.2%). Sixty out of 69 masses were irregular in shape, 6 lobular, 2 ovals and 1 round. Thirty-four showed ill-defined margins, 29 spiculated and 6 microlobulated. Most of them showed a density similar to surrounding fibroglandular tissue. Calcifications were pleomorphic or fine linear in 24 of 30 (80%). Most of cases showed more than 10 flecks and a size greater than 1 cm. Conclusion: The predominant radiologic finding is an irregular, isodense mass those margins tend to share different descriptors, being ill-defined margins the most constant finding. Calcifications representing invasive cancer are predominantly pleomorphic with more than 10 flecks per cm. Architectural distortion and invasive tubular carcinoma are more common than reported in general series

  13. Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

    Directory of Open Access Journals (Sweden)

    Croce MV

    2011-12-01

    Full Text Available Sandra O Demichelis, Marina T Isla-Larrain, Luciano Cermignani, Cecilio G Alberdi, Amada Segal-Eiras, María Virginia CroceCentre of Basic and Applied Immunological Research, Faculty of Medical Sciences, National University of La Plata, La Plata, ArgentinaObjective: In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis.Results: All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased.Conclusion: Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer.Keywords: breast cancer, Argentine women, risk factors, prognostic factors, antigenic expression

  14. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Flemban, Arwa [Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of West of England, Bristol BS16 1QY (United Kingdom); Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Makkah 24382 (Saudi Arabia); Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of West of England, Bristol BS16 1QY (United Kingdom)

    2015-09-16

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT.

  15. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    International Nuclear Information System (INIS)

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT

  16. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    Directory of Open Access Journals (Sweden)

    Arwa Flemban

    2015-09-01

    Full Text Available The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT.

  17. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis.

    Science.gov (United States)

    Flemban, Arwa; Qualtrough, David

    2015-01-01

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT. PMID:26389956

  18. Massive inflammatory reaction following the removal of a ruptured silicone implant masking the invasive breast cancer – case report and literature review

    Directory of Open Access Journals (Sweden)

    Nowaczyk Piotr

    2016-01-01

    Full Text Available This paper presents a case of a patient with invasive ductal breast cancer following breast augmentation. Following breast implants rupture in March 2013 the breast implants have been removed – histopathological examination revealed leaked silicone with inflammatory infiltration, without evidence of cancerous lesions. Diagnostic imaging revealed multiple encapsulated silicone particles and clusters of post-inflammatory macrocalcifications in both breasts. In January 2014 the patient presented with symptoms of massive inflammation of the left breast. Following surgical consultation the patient had undergone radical left-sided mastectomy with lymphadenectomy. Postoperative histopathological examination revealed a multifocal advanced invasive ductal cancer G3 pT3pN3a (vascular invasion, metastases in 11 of 12 examined axillary lymph nodes. Following surgery the patient was qualified for further treatment – chemotherapy, radiotherapy, hormone therapy. The discussion includes a review of literature on the risk evaluation of co-occurrence of breast cancers in women with silicone breast implants and presents diagnostic challenges of breast cancer in this patient group.

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

    Directory of Open Access Journals (Sweden)

    Ping-Hui Sun

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

  20. Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decrease breast cancer cell proliferation, migration, and invasion.

    Science.gov (United States)

    Cao, Maria Dung; Cheng, Menglin; Rizwan, Asif; Jiang, Lu; Krishnamachary, Balaji; Bhujwalla, Zaver M; Bathen, Tone F; Glunde, Kristine

    2016-08-01

    Abnormal choline phospholipid metabolism is associated with oncogenesis and tumor progression. We have investigated the effects of targeting choline phospholipid metabolism by silencing two glycerophosphodiesterase genes, GDPD5 and GDPD6, using small interfering RNA (siRNA) in two breast cancer cell lines, MCF-7 and MDA-MB-231. Treatment with GDPD5 and GDPD6 siRNA resulted in significant increases in glycerophosphocholine (GPC) levels, and no change in the levels of phosphocholine or free choline, which further supports their role as GPC-specific regulators in breast cancer. The GPC levels were increased more than twofold during GDPD6 silencing, and marginally increased during GDPD5 silencing. DNA laddering was negative in both cell lines treated with GDPD5 and GDPD6 siRNA, indicating absence of apoptosis. Treatment with GDPD5 siRNA caused a decrease in cell viability in MCF-7 cells, while GDPD6 siRNA treatment had no effect on cell viability in either cell line. Decreased cell migration and invasion were observed in MDA-MB-231 cells treated with GDPD5 or GDPD6 siRNA, where a more pronounced reduction in cell migration and invasion was observed under GDPD5 siRNA treatment as compared with GDPD6 siRNA treatment. In conclusion, GDPD6 silencing increased the GPC levels in breast cancer cells more profoundly than GDPD5 silencing, while the effects of GDPD5 silencing on cell viability/proliferation, migration, and invasion were more severe than those of GDPD6 silencing. Our results suggest that silencing GDPD5 and GDPD6 alone or in combination may have potential as a new molecular targeting strategy for breast cancer treatment. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27356959

  1. A case-control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer

    OpenAIRE

    Nelson, Stephanie E; Gould, Michael N.; Hampton, John M.; Trentham-Dietz, Amy

    2005-01-01

    Background Overexpression of the HER2 proto-oncogene in human cancer cells has been associated with a poor prognosis, and survival improves with therapy targeting the HER2 gene. Animal studies and protein modeling suggest that the Ile655Val polymorphism located in the transmembrane domain of the HER2 protein might influence breast cancer development by altering the efficiency of homodimerization. Methods To investigate this genetic polymorphism, incident cases of invasive breast cancer (N = 1...

  2. 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).

  3. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro

    Science.gov (United States)

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to 'nd out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast can...

  4. 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 ...

  5. 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

  6. 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 ...

  7. 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, ...

  8. Genome-wide profiling of AP-1-regulated transcription provides insights into the invasiveness of triple-negative breast cancer.

    Science.gov (United States)

    Zhao, Chunyan; Qiao, Yichun; Jonsson, Philip; Wang, Jian; Xu, Li; Rouhi, Pegah; Sinha, Indranil; Cao, Yihai; Williams, Cecilia; Dahlman-Wright, Karin

    2014-07-15

    Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell-cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties.

  9. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Mohamed R Akl

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

  11. Development and Evaluation of a Prediction Model for Underestimated Invasive Breast Cancer in Women with Ductal Carcinoma In Situ at Stereotactic Large Core Needle Biopsy

    OpenAIRE

    Suzanne C E Diepstraten; van de Ven, Stephanie M. W. Y.; Pijnappel, Ruud M; Peeters, Petra H. M.; van den Bosch, Maurice A. A. J.; Helena M Verkooijen; Elias, Sjoerd G

    2013-01-01

    BACKGROUND: We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery. METHODS: From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic lar...

  12. Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein.

    Science.gov (United States)

    Demont, Yohann; Corbet, Cyril; Page, Adeline; Ataman-Önal, Yasemin; Choquet-Kastylevsky, Genevieve; Fliniaux, Ingrid; Le Bourhis, Xuefen; Toillon, Robert-Alain; Bradshaw, Ralph A; Hondermarck, Hubert

    2012-01-13

    The precursor of nerve growth factor (proNGF) has been described as a biologically active polypeptide able to induce apoptosis in neuronal cells, via the neurotrophin receptor p75(NTR) and the sortilin receptor. Herein, it is shown that proNGF is produced and secreted by breast cancer cells, stimulating their invasion. Using Western blotting and mass spectrometry, proNGF was detected in a panel of breast cancer cells as well as in their conditioned media. Immunohistochemical analysis indicated an overproduction of proNGF in breast tumors, when compared with benign and normal breast biopsies, and a relationship to lymph node invasion in ductal carcinomas. Interestingly, siRNA against proNGF induced a decrease of breast cancer cell invasion that was restored by the addition of non-cleavable proNGF. The activation of TrkA, Akt, and Src, but not the MAP kinases, was observed. In addition, the proNGF invasive effect was inhibited by the Trk pharmacological inhibitor K252a, a kinase-dead TrkA, and siRNA against TrkA sortilin, neurotensin, whereas siRNA against p75(NTR) and the MAP kinase inhibitor PD98059 had no impact. These data reveal the existence of an autocrine loop stimulated by proNGF and mediated by TrkA and sortilin, with the activation of Akt and Src, for the stimulation of breast cancer cell invasion.

  13. p130Cas substrate domain signaling promotes migration, invasion, and survival of estrogen receptor-negative breast cancer cells

    Directory of Open Access Journals (Sweden)

    Anna C Cunningham-Edmondson

    2009-12-01

    Full Text Available Anna C Cunningham-Edmondson1,2, Steven K Hanks11Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; 2Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA, USAAbstract: Elevated Src tyrosine kinase activity is commonly observed in breast cancer and likely contributes to neoplasia and malignancy. p130Cas (“Crk-associated substrate” is a major Src substrate found at the sites where integrins mediate cell adhesion to the extracellular matrix. Src phosphorylates multiple tyrosines in the p130Cas “substrate domain” (SD and this signaling event has been implicated in the promotion of cell motility, primarily from studies on fibroblasts. In breast cancer, studies on p130Cas have focused on its role in conferring antiestrogen resistance to cells that express the estrogen receptor (ER+. However, little is known regarding the role of p130Cas in the more aggressive estrogen receptor negative (ER- breast cancers for which there is a need for development of effective targeted therapies. We found high levels of p130Cas SD tyrosine phosphorylation to be a common characteristic of ER- breast cancer cell lines, with particularly high levels observed for the BT-549 cell line. Using RNA interference to knock down p130Cas expression in BT-549 cells, combined with rescue by WT p130Cas versus a signaling-deficient control, we provide evidence that p130Cas SD tyrosine phosphorylation is an important signaling event in the migration, invasion, proliferation, and survival of this ER- breast cancer cell line.Keywords: adhesion, BCAR1, integrins, Src, FAK, tyrosine phosphorylation

  14. Chromodomain Helicase/ATPase DNA-Binding Protein 1-Like Gene (CHD1L Expression and Implications for Invasion and Metastasis of Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Qing-Jie Mu

    Full Text Available Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L, also known as ALC1 (amplified in liver cancer 1 gene, is a new oncogene amplified in many solid tumors. Whether this gene plays a role in invasion and metastasis of breast cancer is unknown.Immunohistochemistry was performed to detect the expression of CHD1L in patients with invasive ductal carcinoma and normal mammary glands. Chemotaxis, wound healing, and Transwell invasion assays were also performed to examine cell migration and invasion. Western blot analysis was conducted to detect the expression of CHD1L, MMP-2, MMP-9, pAkt/Akt, pARK5/ARK5, and pmTOR/mTOR. Moreover, ELISA was carried out to detect the expression levels of MMP-2 and MMP-9. Nude mice xenograft model was used to detect the invasion and metastasis of breast cancer cell lines.CHD1L overexpression was observed in 112 of 268 patients (41.8%. This overexpression was associated with lymph node metastasis (P = 0.008, tumor differentiation (P = 0.020, distant metastasis (P = 0.026, MMP-2 (P = 0.035, and MMP-9 expression (P = 0.022. In the cell experiment, reduction of CHD1L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1L knockdown via siRNA suppressed EGF-induced pAkt, pARK5, and pmTOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.CHD1L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ARK5/mTOR/MMP signaling pathway. This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer.

  15. The invasive lobular carcinoma as a prototype luminal A breast cancer: A retrospective cohort study

    International Nuclear Information System (INIS)

    Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known. We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC). The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T2, 59.8% vs. 38.8%, P = 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P < 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, P < 0.001), progesterone receptor positive (71.1% vs. 50.1%, P < 0.001) and HER2 negative (97.5% vs. 74.6%, P < 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, P < 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, P < 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07). ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC

  16. Small molecule inhibition of arylamine N-acetyltransferase Type I inhibits proliferation and invasiveness of MDA-MB-231 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tiang, Jacky M. [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Butcher, Neville J., E-mail: n.butcher@uq.edu.au [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Minchin, Rodney F. [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia)

    2010-02-26

    Arylamine N-acetyltransferase 1 is a phase II metabolizing enzyme that has been associated with certain breast cancer subtypes. While it has been linked to breast cancer risk because of its role in the metabolic activation and detoxification of carcinogens, recent studies have suggested it may be important in cell growth and survival. To address the possible importance of NAT1 in breast cancer, we have used a novel small molecule inhibitor (Rhod-o-hp) of the enzyme to examine growth and invasion of the breast adenocarcinoma line MDA-MB-231. The inhibitor significantly reduced cell growth by increasing the percent of cells in G2/M phase of the cell cycle. Rhod-o-hp also reduced the ability of the MDA-MB-231 cells to grow in soft agar. Using an in vitro invasion assay, the inhibitor significantly reduced the invasiveness of the cells. To test whether this effect was due to inhibition of NAT1, the enzyme was knocked down using a lentivirus-based shRNA approach and invasion potential was significantly reduced. Taken together, the results of this study demonstrate that NAT1 activity may be important in breast cancer growth and metastasis. The study suggests that NAT1 is a novel target for breast cancer treatment.

  17. LYMPHO-VASCULAR INVASION IN BRCA RELATED BREAST CANCER COMPARED TO SPORADIC CONTROLS

    NARCIS (Netherlands)

    van Voss, M. Heerma; van der Groep, P.; Bart, J.; van der Wall, E.; van Diest, P.

    2010-01-01

    Background: Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways

  18. BSP gene silencing inhibits migration, invasion, and bone metastasis of MDA-MB-231BO human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Jie Wang

    Full Text Available Bone sialoprotein (BSP has been implicated in a variety of physiological and pathophysiological events, including tumor cell invasion, bone homing, adhesion, and matrix degradation. To explore the potential involvement of BSP in human breast cancer cell invasion and metastasis, we used retrovirus-mediated RNAi to deplete BSP levels in the human bone-seeking breast cancer cell line MDA-MB-231BO (231BO and established the 231BO-BSP27 and 231BO-BSP81 cell clones. Cell proliferation, colony formation, wound healing, and the ability to invade into matrigel of these BSP-depleted clones were all decreased. Both 231BO-BSP27 cells and 231BO-BSP81 cells showed a significant (15.4% and 28.6% respectively reduction of bone metastatic potential following intracardiac injection as determined by X-ray detection and by hematoxylin and eosin staining. Moreover, the expression of integrins αvβ3 and β3 was decreased in the BSP-silenced cells whereas ectopic BSP expression increased the integrins αvβ3 and β3 levels. These results together suggest that BSP silencing decreased the integrin αvβ3 and β3 levels, in turn inhibiting cell migration and invasion and decreasing the ability of the cells to metastasize to bone.

  19. Bilateral invasive lobular breast cancer in a female teenager: a rare finding of a common disease - case report and review of literature

    OpenAIRE

    Ndumbe Peter; Ndom Paul; Fongang Emmanuel; Achidi Eric Akum; Asonganyi Etienne Defang; Egbe Obinchemti Thomas; Enow-Orock George Enownchong

    2010-01-01

    Abstract Management of cancer patients in low-resource communities presents enormous challenges. Breast cancer is a public health problem in Cameroon and occurs mostly in elderly women. The predominant histological type is a duct carcinoma. Lobular carcinoma in teenagers is rare. In this report we present a case of bilateral invasive lobular carcinoma of the breast that was confirmed on biopsies in a 22-year-old female. We present this rare finding and review the pathological, clinical and ra...

  20. Low-Grade Inflammation, Oxidative Stress and Risk of Invasive Post-Menopausal Breast Cancer - A Nested Case-Control Study from the Malmo Diet and Cancer Cohort.

    Directory of Open Access Journals (Sweden)

    Joana A Dias

    Full Text Available Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association.In the Malmö Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55-73 years at baseline (1991-96; 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010. In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling we examined systemic inflammation markers: oxidized (ox-LDL, interleukin (IL-1β, IL-6, IL-8, tumor necrosis factor (TNF-α, white blood cells, lymphocytes and neutrophils. Odds ratios (OR and 95% confidence intervals (CI for breast cancer risk was calculated using multivariable conditional logistic regression.Inverse associations with breast cancer were seen in fully-adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI: 0.65 (0.47-0.90, 0.63 (0.45-0.89 respectively, p-trend = 0.01; and for the 3rd tertile of TNF-α, 0.65 (0.43-0.99, p-trend = 0.04. In contrast, those in the highest IL-1β category had higher risk, 1.71 (1.05-2.79, p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer.Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer.

  1. Mammographic, sonographic and MR imaging features of invasive micropapillary breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Alsharif, Shaza; Daghistani, Razan; Kamberoğlu, Elif Aşik; Omeroglu, Atilla; Meterissian, Sarkis; Mesurolle, Benoît, E-mail: benoit.mesurolle@muhc.mcgill.ca

    2014-08-15

    Purpose: Describe mammographic, sonographic and MRI findings of invasive micropapillary carcinoma (IMPC) of the breast. Materials and methods: Review of the pathology database identified 43 patients (mean age, 59.3 years) with the diagnosis of breast IMPC. Three patients had no available imaging studies. Mammograms (40), breast ultrasounds (33) and MRIs (8) were retrospectively evaluated by two radiologists in consensus following the BI-RADS Lexicon. Clinical, histopathologic features, as well as hormone status were recorded. Results: Twenty patients presented with palpable abnormality (20/40, 50%). Thirty-five patients had an abnormal mammogram (87.5%, 35/40) showing 39 lesions, 29 corresponding to masses (29/39, 74.4%), 11 associated with microcalcifications and two associated with architectural distortion. Sonography identified 41 masses (in 33 patients) displaying an irregular shape (30/41, 73.2%), appearing hypoechoic (39/41, 95%), with spiculated or angular margins (26/41, 63.4%), non-parallel orientation (26/41, 63.4%) and combined acoustic posterior pattern (18/41, 44%). MRI identified 13 lesions (in eight patients), 12 as masses (12/13, 92.3%) with irregular or spiculated margins (12/12, 100%), eight displaying an irregular or lobulated shape (8/12, 66.7%), six with homogeneous internal enhancement (6/12, 50%) and eight with type 3 enhancement curve (8/12, 61.5%). Associated non-mass like enhancement was noted in two patients. Twenty-nine patients had associated lymphovascular invasion (29/40, 72.5%) and axillary lymph node metastases were present in 22 of the 39 patients (22/39, 56%). Conclusion: Invasive ductal carcinoma with IMPC features display imaging findings highly suspicious of malignant lesions. They are associated with high lymphovascular invasion and lymph node metastases rates.

  2. Phosphorylation of calcium/calmodulin-stimulated protein kinase II at T286 enhances invasion and migration of human breast cancer cells.

    Science.gov (United States)

    Chi, Mengna; Evans, Hamish; Gilchrist, Jackson; Mayhew, Jack; Hoffman, Alexander; Pearsall, Elizabeth Ann; Jankowski, Helen; Brzozowski, Joshua Stephen; Skelding, Kathryn Anne

    2016-01-01

    Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a multi-functional kinase that controls a range of cellular functions, including proliferation, differentiation and apoptosis. The biological properties of CaMKII are regulated by multi-site phosphorylation. However, the role that CaMKII phosphorylation plays in cancer cell metastasis has not been examined. We demonstrate herein that CaMKII expression and phosphorylation at T286 is increased in breast cancer when compared to normal breast tissue, and that increased CAMK2 mRNA is associated with poor breast cancer patient prognosis (worse overall and distant metastasis free survival). Additionally, we show that overexpression of WT, T286D and T286V forms of CaMKII in MDA-MB-231 and MCF-7 breast cancer cells increases invasion, migration and anchorage independent growth, and that overexpression of the T286D phosphomimic leads to a further increase in the invasive, migratory and anchorage independent growth capacity of these cells. Pharmacological inhibition of CaMKII decreases MDA-MB-231 migration and invasion. Furthermore, we demonstrate that overexpression of T286D, but not WT or T286V-CaMKII, leads to phosphorylation of FAK, STAT5a, and Akt. These results demonstrate a novel function for phosphorylation of CaMKII at T286 in the control of breast cancer metastasis, offering a promising target for the development of therapeutics to prevent breast cancer metastasis. PMID:27605043

  3. Phosphorylation of calcium/calmodulin-stimulated protein kinase II at T286 enhances invasion and migration of human breast cancer cells

    Science.gov (United States)

    Chi, Mengna; Evans, Hamish; Gilchrist, Jackson; Mayhew, Jack; Hoffman, Alexander; Pearsall, Elizabeth Ann; Jankowski, Helen; Brzozowski, Joshua Stephen; Skelding, Kathryn Anne

    2016-01-01

    Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a multi-functional kinase that controls a range of cellular functions, including proliferation, differentiation and apoptosis. The biological properties of CaMKII are regulated by multi-site phosphorylation. However, the role that CaMKII phosphorylation plays in cancer cell metastasis has not been examined. We demonstrate herein that CaMKII expression and phosphorylation at T286 is increased in breast cancer when compared to normal breast tissue, and that increased CAMK2 mRNA is associated with poor breast cancer patient prognosis (worse overall and distant metastasis free survival). Additionally, we show that overexpression of WT, T286D and T286V forms of CaMKII in MDA-MB-231 and MCF-7 breast cancer cells increases invasion, migration and anchorage independent growth, and that overexpression of the T286D phosphomimic leads to a further increase in the invasive, migratory and anchorage independent growth capacity of these cells. Pharmacological inhibition of CaMKII decreases MDA-MB-231 migration and invasion. Furthermore, we demonstrate that overexpression of T286D, but not WT or T286V-CaMKII, leads to phosphorylation of FAK, STAT5a, and Akt. These results demonstrate a novel function for phosphorylation of CaMKII at T286 in the control of breast cancer metastasis, offering a promising target for the development of therapeutics to prevent breast cancer metastasis. PMID:27605043

  4. GIPC1 Interacts with MyoGEF and Promotes MDA-MB-231 Breast Cancer Cell Invasion*

    OpenAIRE

    Wu, Di; Haruta, Akiko; Wei, Qize

    2010-01-01

    GIPC1/synectin, a single PDZ domain-containing protein, binds to numerous proteins and is involved in multiple biological processes, including cell migration. We reported previously that MyoGEF, a guanine nucleotide exchange factor, plays a role in regulating breast cancer cell polarization and invasion. Here, we identify GIPC1 as an interacting partner of MyoGEF. Both in vitro and in vivo binding assays show that the GIPC1 PDZ domain binds to the PDZ-binding motif at the C terminus of MyoGEF...

  5. Gelatin Methacrylate Hydrogels as Biomimetic Three-Dimensional Matrixes for Modeling Breast Cancer Invasion and Chemoresponse in Vitro.

    Science.gov (United States)

    Arya, Anuradha D; Hallur, Pavan M; Karkisaval, Abhijith G; Gudipati, Aditi; Rajendiran, Satheesh; Dhavale, Vaibhav; Ramachandran, Balaji; Jayaprakash, Aravindakshan; Gundiah, Namrata; Chaubey, Aditya

    2016-08-31

    Recent studies have shown that three-dimensional (3D) culture environments allow the study of cellular responses in a setting that more closely resembles the in vivo milieu. In this context, hydrogels have become popular scaffold options for the 3D cell culture. Because the mechanical and biochemical properties of culture matrixes influence crucial cell behavior, selecting a suitable matrix for replicating in vivo cellular phenotype in vitro is essential for understanding disease progression. Gelatin methacrylate (GelMA) hydrogels have been the focus of much attention because of their inherent bioactivity, favorable hydration and diffusion properties, and ease-of-tailoring of their physicochemical characteristics. Therefore, in this study we examined the efficacy of GelMA hydrogels as a suitable platform to model specific attributes of breast cancer. We observed increased invasiveness in vitro and increased tumorigenic ability in vivo in breast cancer cells cultured on GelMA hydrogels. Further, cells cultured on GelMA matrixes were more resistant to paclitaxel treatment, as shown by the results of cell-cycle analysis and gene expression. This study, therefore, validates GelMA hydrogels as inexpensive, cell-responsive 3D platforms for modeling key characteristics associated with breast cancer metastasis, in vitro. PMID:27494432

  6. Ductal carcinoma in situ diagnosed at US-guided 14-gauge core-needle biopsy for breast mass: Preoperative predictors of invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ah Young; Gweon, Hye Mi; Son, Eun Ju; Yoo, Miri; Kim, Jeong-Ah; Youk, Ji Hyun, E-mail: jhyouk@yuhs.ac

    2014-04-15

    Objectives: To identify preoperative features that could be used to predict invasive breast cancer in women with a diagnosis of ductal carcinoma in situ (DCIS) at ultrasound (US)-guided 14-gauge core needle biopsy (CNB). Methods: A total of 86 DCIS lesions that were diagnosed at US-guided 14-gauge CNB and excised surgically in 84 women were assessed. We retrospectively reviewed the patients’ medical records, mammography, US, and MR imaging. We compared underestimation rates of DCIS for the collected clinical and radiologic variables and determined the preoperative predictive factors for upstaging to invasive cancer. Results: Twenty-seven (31.4%) of 86 DCIS lesions were upgraded to invasive cancer. Preoperative features that showed a significantly higher underestimation of DCIS were palpability or nipple discharge (p = 0.040), number of core specimens less than 5 (p = 0.011), mammographic maximum lesion size of 25 mm or larger (p = 0.022), mammographic mass size of 40 mm or larger (p = 0.046), sonographic mass size of 32 mm or larger (p = 0.009), lesion size of 30 mm on MR (p = 0.004), lower signal intensity (SI) on fat-saturated T2-weighted MR images (FS-T2WI) (p = 0.005), heterogeneous or rim enhancement on MR images (p = 0.009), and apparent diffusion coefficient (ADC) values lower than 1.04 × 10{sup −3} mm{sup 2}/s on diffusion-weighted MR imaging (DWI) (p < 0.001). Conclusion: Clinical symptom of palpability or nipple discharge, number of core specimen, mammographic maximum lesion or mass size, SI on FS-T2WI, heterogeneous or rim enhancement on MR, and ADC value may be helpful in predicting the upgrade to invasive breast cancer for DCIS diagnosed at US-guided 14-gauge CNB.

  7. PKCζ Promotes Breast Cancer Invasion by Regulating Expression of E-cadherin and Zonula Occludens-1 (ZO-1) via NFκB-p65

    Science.gov (United States)

    Paul, Arindam; Danley, Marsha; Saha, Biswarup; Tawfik, Ossama; Paul, Soumen

    2015-01-01

    Atypical Protein Kinase C zeta (PKCζ) forms Partitioning-defective (PAR) polarity complex for apico-basal distribution of membrane proteins essential to maintain normal cellular junctional complexes and tissue homeostasis. Consistently, tumor suppressive role of PKCζ has been established for multiple human cancers. However, recent studies also indicate pro-oncogenic function of PKCζ without firm understanding of detailed molecular mechanism. Here we report a possible mechanism of oncogenic PKCζ signaling in the context of breast cancer. We observed that depletion of PKCζ promotes epithelial morphology in mesenchymal-like MDA-MB-231 cells. The induction of epithelial morphology is associated with significant upregulation of adherens junction (AJ) protein E-cadherin and tight junction (TJ) protein Zonula Occludens-1 (ZO-1). Functionally, depletion of PKCζ significantly inhibits invasion and metastatic progression. Consistently, we observed higher expression and activation of PKCζ signaling in invasive and metastatic breast cancers compared to non-invasive diseases. Mechanistically, an oncogenic PKCζ– NFκB-p65 signaling node might be involved to suppress E-cadherin and ZO-1 expression and ectopic expression of a constitutively active form of NFκB-p65 (S536E-NFκB-p65) significantly rescues invasive potential of PKCζ-depleted breast cancer cells. Thus, our study discovered a PKCζ - NFκB-p65 signaling pathway might be involved to alter cellular junctional dynamics for breast cancer invasive progression. PMID:26218882

  8. Expression of p16 and pRB in invasive breast cancer.

    Science.gov (United States)

    Shin, Eunah; Jung, Woo-Hee; Koo, Ja-Seung

    2015-01-01

    We aimed to assess protein expressions of p16 and pRB in breast cancer and explore the clinicopathologic implications. Tissue microarray (TMA) was constructed with 406 cases of breast cancer. The cases were subgrouped into luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) based on the results of immunohistochemical stains for ER, PR, HER-2, and Ki-67 and fluorescent in situ hybridization (FISH) for HER-2. One hundred and sixty-eight cases were allocated to the subgroup luminal A; 87 cases to the luminal B; 32 cases to the HER-2; and 119 cases to the TNBC. The TNBC group showed the highest negative rate for p16, and the luminal B and HER-2 groups showed the highest positive rate for p16 (P pRB expression rate was the highest in the HER-2 group and lowest in the luminal A group. In addition, p16(+)/pRB(+) type was the most common in the luminal B group, p16(+)/pRB(-) in the luminal A group, and p16(-)/pRB(+) in the TNBC group (P pRB(+) and non-altered p16/pRB(+) type was the most common in the luminal B, and altered p16/pRB(-) and non-altered p16/pRB(+) type was the most common in the luminal A (P pRB positivity was correlated with PR negativity (P = 0.009), HER-2 positivity (P = 0.001), and higher Ki-67 LI (P pRB differ according to the molecular subgroups of breast cancer and they subsequently correlate with clnicopathologic factors.

  9. Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Lyng, Maria Bibi; Binder, Harald;

    2014-01-01

    specific algorithm based on the 9 miRNA signature, the risk for future individuals can be predicted. Since microRNAs are highly stable in blood components, this signature might be useful in the development of a blood-based multi-marker test to improve early detection of breast cancer. Such a test could......INTRODUCTION: There are currently no highly sensitive and specific minimally invasive biomarkers for detection of early-stage breast cancer. MicroRNAs (miRNAs) are present in the circulation and may be unique biomarkers for early diagnosis of human cancers. The aim of this study was to investigate...... the differential expression of miRNAs in the serum of breast cancer patients and healthy controls. METHODS: Global miRNA analysis was performed on serum from 48 patients with ER-positive early-stage breast cancer obtained at diagnosis (24 lymph node-positive and 24 lymph node-negative) and 24 age...

  10. ERβ and PEA3 co-activate IL-8 expression and promote the invasion of breast cancer cells.

    Science.gov (United States)

    Chen, Ying; Chen, Li; Li, Ji-Yu; Mukaida, Naofumi; Wang, Qiaoqiao; Yang, Chen; Yin, Wen-Jin; Zeng, Xiao-Hua; Jin, Wei; Shao, Zhi-ming

    2011-03-01

    Metastasis represents the major remaining cause of mortality in human breast cancer. Interleukin-8 (IL-8), a proinflammatory chemokine, plays an important role during tumor angiogenesis and metastasis. In this study, we found that IL-8 and ERβ showed positive association. Overexpression of ERβ or PEA3 could up-regulate IL-8 promoter activity, mRNA and secretion; silencing of ERβ or PEA3 decreased IL-8 mRNA and secretion. ERβ and PEA3 increased IL-8 expression through binding to the IL-8 promoter and increased cell invasion. HER2 could increase ERβ and PEA3 expression and their binding to the IL-8 promoter. We conclude that ERβ and PEA3 play important roles in tumor invasion by regulating IL-8 expression, and HER2 maybe the upstream of ERβ and PEA3 - IL-8 pathway.

  11. Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity

    Directory of Open Access Journals (Sweden)

    Giovanna Ferrari-Amorotti

    2014-12-01

    Full Text Available Most triple-negative breast cancers (TNBCs exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT, a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1; thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic spread of TNBC cell lines. We show here that PCPA treatment induces the expression of E-cadherin and other epithelial markers and markedly suppresses migration and invasion of TNBC cell lines MDA-MB-231 and BT-549. These effects were phenocopied by Slug or LSD1 silencing. In two models of orthotopic breast cancer, PCPA treatment reduced local tumor growth and the number of lung metastases. In mice injected directly in the blood circulation with MDA-MB-231 cells, PCPA treatment or Slug silencing markedly inhibited bone metastases but had no effect on lung infiltration. Thus, blocking Slug activity may suppress the metastatic spread of TNBC and, perhaps, specifically inhibit homing/colonization to the bone.

  12. 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

  13. 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 ...

  14. Bilateral invasive lobular breast cancer in a female teenager: a rare finding of a common disease - case report and review of literature

    Directory of Open Access Journals (Sweden)

    Ndumbe Peter

    2010-07-01

    Full Text Available Management of cancer patients in low-resource communities presents enormous challenges. Breast cancer is a public health problem in Cameroon and occurs mostly in elderly women. The predominant histological type is a duct carcinoma. Lobular carcinoma in teenagers is rare. In this report we present a case of bilateral invasive lobular carcinoma of the breast that was confirmed on biopsies in a 22-year-old female. We present this rare finding and review the pathological, clinical and radiographic challenges of the disease. Nodules in the breast from patients of any age should be submitted for histology. Public education is beneficial and should be intensified

  15. Breast cancer in situ. From pre-malignant lesion of uncertain significance to well-defined non-invasive malignant lesion. The Danish Breast Cancer Cooperative Group Register 1977-2007 revisited

    DEFF Research Database (Denmark)

    Laenkholm, A.V.; Jensen, Maiken Brit; Kroman, N.;

    2008-01-01

    In addition to nationwide standardized pathology forms for operable primary invasive breast cancer, the Danish Breast Cancer cooperative Group (DBCG) in 1982 introduced pathology forms for breast cancer in situ (CIS). The histological reporting form was used primarily for ductal cancer in situ...... receptor (ER) and Progesteron receptor (PR) status. Also mastectomy specimens were included. In 2004 the previous malignancy grading was replaced by the Van Nuys classification, and information on microcalcifications was introduced. The axillary status now included the sentinel node technique only. In 2006...... the pleomorphic subtype of LCIS was added to histological subtypes. The present work reviews the DBCG guidelines and recommendations concerning CIS adding a brief characterization of the Danish CIS population. It also refers to the introduction of modern molecular pathology and distinction between low...

  16. 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.

  17. Comparison of intraoperative frozen section analysis for sentinel lymph node biopsy during breast cancer surgery for invasive lobular carcinoma and invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    Povoski Stephen P

    2009-03-01

    Full Text Available Abstract Background Sentinel lymph node (SLN biopsy is the standard of care for the surgical assessment of the axilla during breast cancer surgery. However, the diagnostic accuracy of intraoperative frozen section analysis for confirming metastatic involvement of SLNs in cases of invasive lobular carcinoma (ILC versus that of invasive ductal carcinoma (IDC has generated controversy secondary to a frequently low-grade cytologic appearance and an often discohesive pattern displayed by metastatic lymph nodes in ILC. In the current report, we present a comparison of intraoperative frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC. Methods We evaluated the results of 131 consecutive cases of ILC from 1997 to 2008 and 133 cases of IDC (selected by a random sequence generator program from amongst 1163 consecutive cases of IDC from the same time period. All cases had at least one SLN that had both intraoperative frozen section analysis and confirmatory permanent section analysis performed. Results No statistically significant difference was found in the sensitivity (67% vs. 75%, P = 0.385, specificity (100% vs. 100%, accuracy (86% vs. 92%, P = 0.172, false negative rate (33% vs. 25%, P = 0.385, negative predictive value (81% vs. 89%, P = 0.158, and positive predictive value (100% vs. 100% for frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC. Conclusion Since there was no statistically significant difference in sensitivity, specificity, accuracy, false negative rate, negative predictive value, and positive predictive value between frozen section analysis of SLNs for patients with ILC and IDC, the clinical accuracy of confirming metastatic involvement of SLNs on frozen section analysis for ILC should not be considered inferior to the clinical accuracy for IDC. Therefore, frozen section analysis

  18. Inhibition of MDA-MB-231 breast cancer cell migration and invasion activity by andrographolide via suppression of nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

    Science.gov (United States)

    Zhai, Zanjing; Qu, Xinhua; Li, Haowei; Ouyang, Zhengxiao; Yan, Wei; Liu, Guangwang; Liu, Xuqiang; Fan, Qiming; Tang, Tingting; Dai, Kerong; Qin, An

    2015-02-01

    Breast cancer is one of the most common types of cancer worldwide. The majority of patients with cancer succumb to the disease as a result of distant metastases (for example, in the bones), which cause severe complications. Despite advancements in breast cancer treatment, chemotherapeutic outcomes remain far from satisfactory, prompting a search for effective natural agents with few side‑effects. Andrographolide (AP), a natural diterpenoid lactone isolated from Andrographis paniculata, inhibits cancer cell growth. The current study aimed to examine the effect of AP on breast cancer cell proliferation, survival and progression in vitro and also its inhibitory activity on breast cancer bone metastasis in vivo. To achieve this, CCK8, flow cytometry, migration, invasion, western blot, PCR and luciferase reporter assay analyses were performed in vitro as well as establishing intratibial xenograft model of breast cancer bone metastasis in vivo. The results demonstrated that AP inhibits the migration and invasion of the MBA‑MD‑231 aggressive breast cancer cell line at non‑lethal concentrations, in addition to suppressing proliferation and inducing apoptosis at high concentrations in vitro. In vivo, AP significantly inhibited the growth of tumors planted in bone and attenuated cancer‑induced osteolysis. Tartrate‑resistant acid phosphatase staining revealed osteoclast activation in tumor‑bearing mice and AP was observed to attenuate this activation. The anti‑tumor activity of AP in vitro and in vivo correlates with the downregulation of the nuclear factor κB signaling pathway and the inhibition of matrix metalloproteinase‑9 expression levels. These results indicate that AP may be an effective anti‑tumor agent for the treatment of breast cancer bone metastasis. PMID:25374279

  19. Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2016-02-01

    Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

  20. Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2016-02-01

    Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP. PMID:26715289

  1. Basal Subtype of Invasive Breast Cancer Is Associated With a Higher Risk of True Recurrence After Conventional Breast-Conserving Therapy

    International Nuclear Information System (INIS)

    Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1–T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT). Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1–T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ or PR+ and HER-2 negative [HER-2−]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER− and PR− and HER-2+), and basal (ER− and PR− and HER-2− ) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR. Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8, p = 0.01), younger age at diagnosis (HR, 0.97; p = 0.05), and increasing tumor size (HR, 2.1; p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95; p = 0.01) significantly predicted for ELR. Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1–T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce

  2. Basal Subtype of Invasive Breast Cancer Is Associated With a Higher Risk of True Recurrence After Conventional Breast-Conserving Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hattangadi-Gluth, Jona A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Wo, Jennifer Y. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Nguyen, Paul L. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Abi Raad, Rita F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Sreedhara, Meera [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Freer, Phoebe E. [Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Georgian-Smith, Dianne [Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Bellon, Jennifer R.; Wong, Julia S. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Smith, Barbara L. [Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Harris, Jay R. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2012-03-01

    Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1-T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT). Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1-T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ or PR+ and HER-2 negative [HER-2-]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER- and PR- and HER-2+), and basal (ER- and PR- and HER-2- ) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR. Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8, p = 0.01), younger age at diagnosis (HR, 0.97; p = 0.05), and increasing tumor size (HR, 2.1; p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95; p = 0.01) significantly predicted for ELR. Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1-T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce TR in basal

  3. Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells

    Directory of Open Access Journals (Sweden)

    Wernet Peter

    2010-08-01

    Full Text Available Abstract Background The miR-200c/141 cluster has recently been implicated in the epithelial to mesenchymal transition (EMT process. The expression of these two miRNAs is inversely correlated with tumorigenicity and invasiveness in several human cancers. The role of these miRNAs in cancer progression is based in part on their capacity to target the EMT activators ZEB1 and ZEB2, two transcription factors, which in turn repress expression of E-cadherin. Little is known about the regulation of the mir200c/141 cluster, whose targeting has been proposed as a promising new therapy for the most aggressive tumors. Findings We show that the miR-200c/141 cluster is repressed by DNA methylation of a CpG island located in the promoter region of these miRNAs. Whereas in vitro methylation of the miR-200c/141 promoter led to shutdown of promoter activity, treatment with a demethylating agent caused transcriptional reactivation in breast cancer cells formerly lacking expression of miR-200c and miR-141. More importantly, we observed that DNA methylation of the identified miR-200c/141 promoter was tightly correlated with phenotype and the invasive capacity in a panel of 8 human breast cancer cell lines. In line with this, in vitro induction of EMT by ectopic expression of the EMT transcription factor Twist in human immortalized mammary epithelial cells (HMLE was accompanied by increased DNA methylation and concomitant repression of the miR-200c/141 locus. Conclusions The present study demonstrates that expression of the miR-200c/141 cluster is regulated by DNA methylation, suggesting epigenetic regulation of this miRNA locus in aggressive breast cancer cell lines as well as untransformed mammary epithelial cells. This epigenetic silencing mechanism might represent a novel component of the regulatory circuit for the maintenance of EMT programs in cancer and normal cells.

  4. 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 ...

  5. 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 ...

  6. 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. ...

  7. Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs

    Directory of Open Access Journals (Sweden)

    Ringnér Markus

    2008-07-01

    Full Text Available Abstract Background Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors. Methods 32 K tiling microarray-based comparative genomic hybridization (aCGH was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters. Results Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 × 10-5 unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29 displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses. Conclusion Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and

  8. Breast conserving treatment for breast cancer: dosimetric comparison of different non-invasive techniques for additional boost delivery

    International Nuclear Information System (INIS)

    Today it is unclear which technique for delivery of an additional boost after whole breast radiotherapy for breast conserved patients should be state of the art. We present a dosimetric comparison of different non-invasive treatment techniques for additional boost delivery. For 10 different tumor bed localizations, 7 different non-invasive treatment plans were made. Dosimetric comparison of PTV-coverage and dose to organs at risk was performed. The Vero system achieved an excellent PTV-coverage and at the same time could minimize the dose to the organs at risk with an average near-maximum-dose (D2) to the heart of 0.9 Gy and the average volume of ipsilateral lung receiving 5 Gy (V5) of 1.5%. The TomoTherapy modalities delivered an average D2 to the heart of 0.9 Gy for the rotational and of 2.3 Gy for the static modality and an average V5 to the ipsilateral lung of 7.3% and 2.9% respectively. A rotational technique offers an adequate conformity at the cost of more low dose spread and a larger build-up area. In most cases a 2-field technique showed acceptable PTV-coverage, but a bad conformity. Electrons often delivered a worse PTV-coverage than photons, with the planning requirements achieved only in 2 patients and with an average D2 to the heart of 2.8 Gy and an average V5 to the ipsilateral lung of 5.8%. We present advices which can be used as guidelines for the selection of the best individualized treatment

  9. Diagnosis of breast cancer by tissue analysis

    Institute of Scientific and Technical Information of China (English)

    Debnath Bhattacharyya; Samir Kumar Bandyopadhyay; Tai-hoon Kim

    2013-01-01

    In this paper,we propose a technique to locate abnormal growth of cells in breast tissue and suggest further pathological test,when require.We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps.Normal ductal epithelial cells and ductal/lobular invasive carcinogenic cells also consider for comparison here in this paper.In fact,features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue.We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some extent.

  10. Effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences after treatment for early-stage invasive breast cancer : A meta-analysis and systematic review

    NARCIS (Netherlands)

    de Bock, GH; Bonnema, J; van der Hage, J; Kievit, J; van de Velde, CJH

    2004-01-01

    Purpose To review the effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences in asymptomatic patients after treatment for early-stage invasive breast cancer. Methods Systematic review and meta-analysis. The proportion of isolated locoregional recurrences dia

  11. Zerumbone suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells.

    Science.gov (United States)

    Han, Jeonghun; Bae, Soo Youn; Oh, Soo-Jin; Lee, Jeongmin; Lee, Jun Ho; Lee, Hyun-Chul; Lee, Se Kyung; Kil, Won Ho; Kim, Seok Won; Nam, Seok Jin; Kim, Sangmin; Lee, Jeong Eon

    2014-11-01

    Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)-1β is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL-1β-induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL-1β-induced cell migration and invasion in breast cancer cells. The levels of IL-8 and matrix metalloproteinase (MMP)-3 mRNA were analyzed by real-time polymerase chain reaction. The levels of secreted IL-8 and MMP-3 protein were analyzed by enzyme-linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL-8 and MMP-3 expression were significantly increased by IL-1β treatment in Hs578T and MDA-MB231 cells. On the other hand, IL-1β-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL-1β-induced cell migration and invasion were decreased by ZER in Hs578T and MDA-MB231 cells. ZER suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 expression and MMP-3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple-negative breast cancer patients.

  12. Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells.

    Science.gov (United States)

    Park, Geun-Soo; Kim, Jae-Hong

    2015-03-20

    Inflammation and local inflammatory mediators are inextricably linked to tumor progression through complex pathways in the tumor microenvironment. Lipopolysaccharide (LPS) exposure to tumor cells has been suggested to promote tumor invasiveness and metastasis. However, the detailed signaling mechanism involved has not been elucidated. In this study, we showed that LPS upregulated the expression of leukotriene B4 receptor-2 (BLT2) and the synthesis of BLT2 ligands in MDA-MB-231 and MDA-MB-435 breast cancer cells, thereby promoting invasiveness. BLT2 depletion with siRNA clearly attenuated LPS-induced invasiveness. In addition, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies upstream of BLT2 in LPS-potentiated invasiveness and that this 'MyD88-BLT2' cascade mediates activation of NF-κB and the synthesis of IL-6 and IL-8, which are critical for the invasiveness and aggression of breast cancer cells. LPS-driven metastasis of MDA-MB-231 cells was also markedly suppressed by the inhibition of BLT2. Together, our results demonstrate, for the first time, that LPS potentiates the invasiveness and metastasis of breast cancer cells via a 'MyD88-BLT2'-linked signaling cascade.

  13. Strong adverse effect of epidermal growth factor receptor 2 overexpression on prognosis of patients with invasive lobular breast cancer: a comparative study with invasive ductal breast cancer in Chinese population.

    Science.gov (United States)

    Wang, Tong; Ma, Yuanyuan; Wang, Liang; Liu, Hong; Chen, Meixuan; Niu, Ruifang

    2015-08-01

    The data on the outcome of breast invasive lobular carcinoma (ILC) are conflicting. In addition, the prognostic effect of molecular subtypes on ILC remains unclear. In this study, the clinicopathological and prognostic data between 269 ILC and 816 invasive ductal carcinoma (IDC) cases in a Chinese population were extensively compared, with a median follow-up time of 7.8 years. Compared with the IDC group, ILC tumors had more lymph node invasion, hormonal receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity. ILC patients showed overall survival (OS) and recurrence/metastasis-free survival (RFS) rates similar to those of IDC patients but exhibited worse disease-free survival (DFS) rate because of the higher rate of contralateral breast cancer (BC). Further analysis showed that OS, RFS, and DFS were similar between ILC and IDC patients in the subgroups of luminal A and triple-negative BC with HER2 negativity but were worse in ILC patients than those in IDC patients in the subgroups of luminal B and HER2 overexpression with positive HER2 expression. Multivariate analysis indicated HER2 positivity as an independent risk factor for OS, RFS, and DFS of ILC patients, which increased the risk in the ILC group than that in IDC group. The interaction of HER2 and ILC was also defined as an independent risk factor for OS, RFS, and DFS of the entire population. In conclusion, overexpression of HER2 exhibited stronger negative effect on the prognosis of ILC patients than that in IDC patients, suggesting that treatment targeting HER2 is crucial for this BC subgroup. PMID:25804795

  14. Interleukin-19 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2013-01-01

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

  15. Invasive breast cancer following bilateral subcutaneous mastectomy in a BRCA2 mutation carrier: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Galvez Maria

    2005-08-01

    Full Text Available Abstract Background Primary prevention of breast cancer through prophylactic mastectomy can reduce the risk of malignancy in high-risk individuals. No type of mastectomy completely removes all breast tissue, but a subcutaneous mastectomy leaves more tissue in situ than does a simple mastectomy. Case presentation We report a case of invasive breast cancer in a BRCA2-positive woman 33 years after bilateral subcutaneous mastectomy. To our knowledge, only one case of primary breast cancer after prophylactic mastectomy in a BRCA1-positive patient has been reported in the literature and none in BRCA2-positive individuals. Conclusion Careful documentation and long follow-up is essential to fully assess the benefits and risks of preventive surgical procedures in BRCA1 and BRCA2 mutation carriers.

  16. Bioguided discovery and pharmacophore modeling of the mycotoxic indole diterpene alkaloids penitrems as breast cancer proliferation, migration, and invasion inhibitors

    Science.gov (United States)

    Sallam, Asmaa A.; Houssen, Wael E.; Gissendanner, Chris R.; Orabi, Khaled Y.; Foudah, Ahmed I.; El Sayed, Khalid A.

    2013-01-01

    Marine-derived fungi have proven to be important sources of bioactive natural organohalides. The genus Penicillium is recognized as a rich source of chemically diverse bioactive secondary metabolites. This study reports the fermentation, isolation and identification of a marine-derived Penicillium species. Bioassay-guided fractionation afforded the indole diterpene alkaloids penitrems A, B, D, E and F as well as paspaline and emnidole SB (1–7). Supplementing the fermentation broth of the growing fungus with KBr afforded the new 6-bromopenitrem B (8) and the known 6-bromopenitrem E (9). These compounds showed good antiproliferative, antimigratory and anti-invasive properties against human breast cancer cells. Penitrem B also showed a good activity profile in the NCI-60 DTP human tumor cell line screen. The nematode Caenorhabditis elegans was used to assess the BK channel inhibitory activity and toxicity of select compounds. A pharmacophore model was generated to explain the structural relationships of 1–9 with respect to their antiproliferative activity against the breast cancer MCF-7 cells. The structurally less complex biosynthetic precursors, paspaline (6) and emindole SB (7), were identified as potential hits suitable for future studies. PMID:24273638

  17. c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis

    Directory of Open Access Journals (Sweden)

    Knopfová Lucia

    2012-03-01

    Full Text Available Abstract Background The c-Myb transcription factor is essential for the maintenance of stem-progenitor cells in bone marrow, colon epithelia, and neurogenic niches. c-Myb malfunction contributes to several types of malignancies including breast cancer. However, the function of c-Myb in the metastatic spread of breast tumors remains unexplored. In this study, we report a novel role of c-Myb in the control of specific proteases that regulate the matrix-dependent invasion of breast cancer cells. Results Ectopically expressed c-Myb enhanced migration and ability of human MDA-MB-231 and mouse 4T1 mammary cancer cells to invade Matrigel but not the collagen I matrix in vitro. c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP 9 and significantly downregulated MMP1. The gene coding for cathepsin D was suggested as the c-Myb-responsive gene and downstream effector of the migration-promoting function of c-Myb. Finally, we demonstrated that c-Myb delayed the growth of mammary tumors in BALB/c mice and affected the metastatic potential of breast cancer cells in an organ-specific manner. Conclusions This study identified c-Myb as a matrix-dependent regulator of invasive behavior of breast cancer cells.

  18. Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions

    Institute of Scientific and Technical Information of China (English)

    Wei Yan; Bing Tu; Yun-yun Liu; Ting-yu Wang; Han Qiao; Zan-jing Zhai; Hao-wei Li; Ting-ting Tang

    2013-01-01

    Objective:The aim of this study was to investigate the effects of plumbagin (PL), a naphthoquinone derived from the medicinal plant plumbago zeylanica, on the invasion and migration of human breast cancer cells. Methods:Human breast cancer MDA-MB-231SArfp cells were treated with different concentrations of plum-bagin for 24 h. The effects of plumbagin on the migration and invasion were observed by a transwell method. The expressions of IL-1α, IL-1β, IL-6, IL-8, TGF-β, TNFα, MMP-2 and MMP-9 mRNA in M DA-MB-231SArfp cells were detected using Real-Time PCR. MDA-MB-231SArfp cells were treated with plumbagin at different concentrations for 45 minutes. The activation of STAT3 was detected by western blot. Following this analysis, STAT3 in MDA-MB-231SArfp cells was knocked out using specific siRNA. mRNA levels of IL-1α, TGF-β, MMP-2 and MMP-9 were then detected. Consequently, MDA-MB-231SArfp cells were injected intracardially into BALB/c nude mice to construct a breast cancer bone metastatic model. The mice were injected intra-peritoneally with plumbagin. Non-invasive in vivo monitoring, X-ray imaging and histological staining were performed to investigate the effects of plumbagin on the invasion and migration of breast cancer cells in vivo. Results: The in vitro results showed that plumbagin could suppress the migration and invasion of breast cancer cells and down-regulate mRNA expressions of IL-1α, TGF-β, MMP-2 and MMP-9. Western blotting demonstrated that plumbagin inhibited the activation of STAT3 signaling in MDA-MB-231SArfp cells. The inactivation of STAT3 was found to have an inhibitory effect on the expressions of IL-1α, TGF-β, MMP-2 and MMP-9. In vivo studies showed that plumbagin inhibited the metastasis of breast cancer cells and decreased osteolytic bone metastases, as well as the secretion of MMP-2 and MMP-9 by tumor cells at metastatic lesions. Conclusions:Plumbagin can suppress the invasion and migration of breast cancer cells via the inhibition

  19. Upregulated WDR26 serves as a scaffold to coordinate PI3K/ AKT pathway-driven breast cancer cell growth, migration, and invasion.

    Science.gov (United States)

    Ye, Yuanchao; Tang, Xiaoyun; Sun, Zhizeng; Chen, Songhai

    2016-04-01

    The phosphatidylinositol 3-kinase (PI3K)/AKT pathway transmits signals downstream of receptor tyrosine kinases and G protein-coupled receptors (GPCRs), and is one of the most dysregulated pathways in breast cancer. PI3Ks and AKTs consist of multiple isoforms that play distinct and even opposite roles in breast cancer cell growth and metastasis. However, it remains unknown how the activities of various PI3K and AKT isoforms are coordinated during breast cancer progression. Previously, we showed WDR26 is a novel WD40 protein that binds Gβγ and promotes Gβγ signaling. Here, we demonstrate that WDR26 is overexpressed in highly malignant breast tumor cell lines and human breast cancer samples, and that WDR26 overexpression correlates with shortened survival of breast cancer patients. In highly malignant cell lines (MDA-MB231, DU4475 and BT549), downregulation of WDR26 expression selectively alleviated GPCR- but not EGF receptor-stimulated PI3K/AKT signaling and tumor cell growth, migration and invasion. In contrast, in a less malignant cell line (MCF7), WDR26 overexpression had the opposite effect. Additional studies indicate that downstream of GPCR stimulation, WDR26 serves as a scaffold that fosters assembly of a specific signaling complex consisting of Gβγ, PI3Kβ and AKT2. In an orthotopic xenograft mouse model of breast cancer, disrupting formation of this complex, by overexpressing WDR26 mutants in MDA-MB231 cells, abrogated PI3K/AKT activation and tumor cell growth and metastasis. Together, our results identify a novel mechanism regulating GPCR-dependent activation of the PI3K/AKT signaling axis in breast tumor cells, and pinpoint WDR26 as a potential therapeutic target for breast cancer.

  20. Risk assessment model for invasive breast cancer in Hong Kong women

    Science.gov (United States)

    Wang, Feng; Dai, Juncheng; Li, Mengjie; Chan, Wing-cheong; Kwok, Carol Chi-hei; Leung, Siu-lan; Wu, Cherry; Li, Wentao; Yu, Wai-cho; Tsang, Koon-ho; Law, Sze-hong; Lee, Priscilla Ming-yi; Wong, Carmen Ka-man; Shen, Hongbing; Wong, Samuel Yeung-shan; Yang, Xiaohong R.; Tse, Lap Ah

    2016-01-01

    Abstract No risk assessment tool is available for identifying high risk population of breast cancer (BCa) in Hong Kong. A case–control study including 918 BCa cases and 923 controls was used to develop the risk assessment model among Hong Kong Chinese women. Each participant received an in-depth interview to obtain their lifestyle and environmental risk factors. Least absolute shrinkage and selection operator (LASSO) selection model was used to select the optimal risk factors (LASSO-model). A risk score system was constructed to evaluate the cumulative effects of selected factors. Bootstrap simulation was used to test the internal validation of the model. Model performance was evaluated by receiver-operator characteristic curves and the area under the curve (AUC). Age, number of parity, number of BCa cases in 1st-degree relatives, exposure to light at night, and sleep quality were the common risk factors for all women. Alcohol drinking was included for premenopausal women; body mass index, age at menarche, age at 1st give birth, breast feeding, using of oral contraceptive, hormone replacement treatment, and history of benign breast diseases were included for postmenopausal women. The AUCs were 0.640 (95% CI, 0.598–0.681) and 0.655 (95% CI, 0.621–0.653) for pre- and postmenopausal women, respectively. Further subgroup evaluation revealed that the model performance was better for women aged 50 to 70 years or ER-positive. This BCa risk assessment tool in Hong Kong Chinese women based on LASSO selection is promising, which shows a slightly higher discriminative accuracy than those developed in other populations. PMID:27512870

  1. Risk assessment model for invasive breast cancer in Hong Kong women.

    Science.gov (United States)

    Wang, Feng; Dai, Juncheng; Li, Mengjie; Chan, Wing-Cheong; Kwok, Carol Chi-Hei; Leung, Siu-Lan; Wu, Cherry; Li, Wentao; Yu, Wai-Cho; Tsang, Koon-Ho; Law, Sze-Hong; Lee, Priscilla Ming-Yi; Wong, Carmen Ka-Man; Shen, Hongbing; Wong, Samuel Yeung-Shan; Yang, Xiaohong R; Tse, Lap Ah

    2016-08-01

    No risk assessment tool is available for identifying high risk population of breast cancer (BCa) in Hong Kong. A case-control study including 918 BCa cases and 923 controls was used to develop the risk assessment model among Hong Kong Chinese women.Each participant received an in-depth interview to obtain their lifestyle and environmental risk factors. Least absolute shrinkage and selection operator (LASSO) selection model was used to select the optimal risk factors (LASSO-model). A risk score system was constructed to evaluate the cumulative effects of selected factors. Bootstrap simulation was used to test the internal validation of the model. Model performance was evaluated by receiver-operator characteristic curves and the area under the curve (AUC).Age, number of parity, number of BCa cases in 1st-degree relatives, exposure to light at night, and sleep quality were the common risk factors for all women. Alcohol drinking was included for premenopausal women; body mass index, age at menarche, age at 1st give birth, breast feeding, using of oral contraceptive, hormone replacement treatment, and history of benign breast diseases were included for postmenopausal women. The AUCs were 0.640 (95% CI, 0.598-0.681) and 0.655 (95% CI, 0.621-0.653) for pre- and postmenopausal women, respectively. Further subgroup evaluation revealed that the model performance was better for women aged 50 to 70 years or ER-positive.This BCa risk assessment tool in Hong Kong Chinese women based on LASSO selection is promising, which shows a slightly higher discriminative accuracy than those developed in other populations. PMID:27512870

  2. Breast cancer in situ. From pre-malignant lesion of uncertain significance to well-defined non-invasive malignant lesion

    DEFF Research Database (Denmark)

    Laenkholm, Anne-Vibeke; Jensen, Maj-Britt; Kroman, Niels;

    2008-01-01

    In addition to nationwide standardized pathology forms for operable primary invasive breast cancer, the Danish Breast Cancer cooperative Group (DBCG) in 1982 introduced pathology forms for breast cancer in situ (CIS). The histological reporting form was used primarily for ductal cancer in situ...... receptor (ER) and Progesteron receptor (PR) status. Also mastectomy specimens were included. In 2004 the previous malignancy grading was replaced by the Van Nuys classification, and information on microcalcifications was introduced. The axillary status now included the sentinel node technique only. In 2006...... the pleomorphic subtype of LCIS was added to histological subtypes. The present work reviews the DBCG guidelines and recommendations concerning CIS adding a brief characterization of the Danish CIS population. It also refers to the introduction of modern molecular pathology and distinction between low...

  3. 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 ...

  4. Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB‑231 partly through suppression of the Akt pathway.

    Science.gov (United States)

    Jin, Hana; Lee, Won Sup; Eun, So Young; Jung, Ji Hyun; Park, Hyeon-Soo; Kim, Gonsup; Choi, Yung Hyun; Ryu, Chung Ho; Jung, Jin Myung; Hong, Soon Chan; Shin, Sung Chul; Kim, Hye Jung

    2014-10-01

    Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB‑231 breast cancer cells from low doses (50 µM) without cytotoxicity. In addition, morin changed MDA-MB‑231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB‑231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB‑231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB‑231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB‑231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.

  5. Radiotherapy in the management of early breast cancer

    OpenAIRE

    Wang, Wei

    2013-01-01

    Radiotherapy is an indispensible part of the management of all stages of breast cancer. In this article, the common indications for radiotherapy in the management of early breast cancer (stages 0, I, and II) are reviewed, including whole-breast radiotherapy as part of breast-conserving treatment for early invasive breast cancer and pre-invasive disease of ductal carcinoma in situ, post-mastectomy radiotherapy, locoregional radiotherapy, and partial breast irradiation. Key clinical studies tha...

  6. Analysis of factors influencing the degree of detectability on diffusion-weighted MRI and diffusion background signals in patients with invasive breast cancer.

    Science.gov (United States)

    Hahn, Soo Yeon; Ko, Eun Sook; Han, Boo-Kyung; Lim, Yaeji; Gu, Seonhye; Ko, Eun Young

    2016-07-01

    To determine the factors influencing the degree of detectability of lesions and diffusion background signals on magnetic resonance diffusion-weighted imaging (DWI) in invasive breast cancer.Institutional review board approval was obtained and patient consent was waived. Patients with newly diagnosed invasive ductal carcinoma, who underwent preoperative breast magnetic resonance imaging with DWI were included in this study (n = 167). Lesion detectability on DWI and contrast-enhanced subtracted T1-weighted images, the degree of background parenchymal enhancement (BPE), and diffusion background signal were qualitatively rated. Detectability of lesions on DWI was compared with clinicopathological findings including menopausal status, mammographic density, and molecular subtype of breast cancer. Multivariate linear regression analysis was performed to determine variables independently associated with detectability of lesions on DWI and diffusion background signals.Univariate analysis showed that the detectability of lesions on DWI was significantly associated with lesion size (P = 0.001), diffuse background signal (P breast cancer. Only BPE was correlated with the amount of diffusion background signal on DWI (P breast cancers, detectability on DWI was significantly affected by the diffusion background signal. BPE, menopausal status, menstrual cycle, or mammographic density did not show statistically significant correlation with the diffusion detectability of lesions on DWI. PMID:27399100

  7. 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 ...

  8. Bisphenol A Increases the Migration and Invasion of Triple-Negative Breast Cancer Cells via Oestrogen-related Receptor Gamma.

    Science.gov (United States)

    Zhang, Xiao-Lin; Liu, Na; Weng, Shan-Fan; Wang, Hong-Sheng

    2016-10-01

    Triple-negative breast cancer (TNBC) is characterized by great metastasis and invasion capability. Our study revealed that nanomolar bisphenol A (BPA), one of the most ubiquitous endocrine disruptors, can increase wound closure and invasion of both MDA-MB-231 and BT-549 cells. BPA treatment can increase protein and mRNA expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, while had no effect on the expression of vimentin (Vim) and fibronectin (FN) in TNBC cells. The expression of G-protein-coupled receptor (GPER), which has been suggested to mediate rapid oestrogenic signals, was not varied in BPA-treated MDA-MB-231 and BT-549 cells. Its inhibitor G15 also had no effect on BPA-induced MMPs expression and cell invasion. Interestingly, BPA treatment can significantly increase the mRNA and protein expressions of oestrogen-related receptor γ (ERRγ), but not ERRα or ERRβ, in both MDA-MB-231 and BT-549 cells. The knock-down of ERRγ can markedly attenuate BPA-induced expression of MMP-2 and MMP-9 in TNBC cells. BPA treatment can activate both ERK1/2 and Akt in TNBC cells. Both inhibitors of ERK1/2 (PD98059) and Akt (LY294002) can attenuate BPA-induced ERRγ expression and cell invasion of MDA-MB-231 cells. Collectively, our data revealed that BPA can increase the expression of MMPs and in vitro motility of TNBC cells via ERRγ. Both activation of ERK1/2 and Akt participated in this process. Our study suggests that more attention should be paid to the roles of xenoestrogens such as BPA in the development and progression of TNBC. PMID:27038254

  9. Shear-wave elastography and immunohistochemical profiles in invasive breast cancer: Evaluation of maximum and mean elasticity values

    Energy Technology Data Exchange (ETDEWEB)

    Ganau, Sergi, E-mail: sganau@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Andreu, Francisco Javier, E-mail: xandreu@tauli.cat [Pathology Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Escribano, Fernanda, E-mail: fescribano@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Martín, Amaya, E-mail: amartino@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Tortajada, Lidia, E-mail: ltortajada@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Villajos, Maite, E-mail: mvillajos@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); and others

    2015-04-15

    Highlights: •Shear wave elastography provides a quantitative assessment of the hardness of breast lesions. •The hardness of breast lesions correlates with lesion size: larger lesions are harder than smaller ones. •Histologic type and grade do not correlate clearly with elastography parameters. •HER2, luminal B HER2+, and triple-negative tumors have lower maximum hardness and mean hardness than other tumor types. •Half the tumors classified as BI-RADS 3 were luminal A and half were HER2. -- Abstract: Purpose: To evaluate the correlations of maximum stiffness (Emax) and mean stiffness (Emean) of invasive carcinomas on shear-wave elastography (SWE) with St. Gallen consensus tumor phenotypes. Methods: We used an ultrasound system with SWE capabilities to prospectively study 190 women with 216 histologically confirmed invasive breast cancers. We obtained one elastogram for each lesion. We correlated Emax and Emean with tumor size, histologic type and grade, estrogen and progesterone receptors, HER2 expression, the Ki67 proliferation index, and the five St. Gallen molecular subtypes: luminal A, luminal B without HER2 overexpression (luminal B HER2−), luminal B with HER2 overexpression (luminal B HER2+), HER2, and triple negative. Results: Lesions larger than 20 mm had significantly higher Emax (148.04 kPa) and Emean (118.32 kPa) (P = 0.005) than smaller lesions. We found no statistically significant correlations between elasticity parameters and histologic type and grade or molecular subtypes, although tumors with HER2 overexpression regardless whether they expressed hormone receptors (luminal B HER2+ and HER2 phenotypes) and triple-negative tumors had lower Emax and Emean than the others. We assessed the B-mode ultrasound findings of the lesions with some of the Emax or Emean values less than or equal to 80 kPa; only four of these had ultrasound findings suggestive of a benign lesion (two with luminal A phenotype and two with HER2 phenotype). Conclusions: We

  10. Shear-wave elastography and immunohistochemical profiles in invasive breast cancer: Evaluation of maximum and mean elasticity values

    International Nuclear Information System (INIS)

    Highlights: •Shear wave elastography provides a quantitative assessment of the hardness of breast lesions. •The hardness of breast lesions correlates with lesion size: larger lesions are harder than smaller ones. •Histologic type and grade do not correlate clearly with elastography parameters. •HER2, luminal B HER2+, and triple-negative tumors have lower maximum hardness and mean hardness than other tumor types. •Half the tumors classified as BI-RADS 3 were luminal A and half were HER2. -- Abstract: Purpose: To evaluate the correlations of maximum stiffness (Emax) and mean stiffness (Emean) of invasive carcinomas on shear-wave elastography (SWE) with St. Gallen consensus tumor phenotypes. Methods: We used an ultrasound system with SWE capabilities to prospectively study 190 women with 216 histologically confirmed invasive breast cancers. We obtained one elastogram for each lesion. We correlated Emax and Emean with tumor size, histologic type and grade, estrogen and progesterone receptors, HER2 expression, the Ki67 proliferation index, and the five St. Gallen molecular subtypes: luminal A, luminal B without HER2 overexpression (luminal B HER2−), luminal B with HER2 overexpression (luminal B HER2+), HER2, and triple negative. Results: Lesions larger than 20 mm had significantly higher Emax (148.04 kPa) and Emean (118.32 kPa) (P = 0.005) than smaller lesions. We found no statistically significant correlations between elasticity parameters and histologic type and grade or molecular subtypes, although tumors with HER2 overexpression regardless whether they expressed hormone receptors (luminal B HER2+ and HER2 phenotypes) and triple-negative tumors had lower Emax and Emean than the others. We assessed the B-mode ultrasound findings of the lesions with some of the Emax or Emean values less than or equal to 80 kPa; only four of these had ultrasound findings suggestive of a benign lesion (two with luminal A phenotype and two with HER2 phenotype). Conclusions: We

  11. A case-control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer

    International Nuclear Information System (INIS)

    Overexpression of the HER2 proto-oncogene in human cancer cells has been associated with a poor prognosis, and survival improves with therapy targeting the HER2 gene. Animal studies and protein modeling suggest that the Ile655Val polymorphism located in the transmembrane domain of the HER2 protein might influence breast cancer development by altering the efficiency of homodimerization. To investigate this genetic polymorphism, incident cases of invasive breast cancer (N = 1,094) and population controls of a similar age (N = 976) were interviewed during 2001 to 2003 regarding their risk factors for breast cancer. By using DNA collected from buccal samples mailed by the participants, the HER2 Ile655Val polymorphism was evaluated with the Applied Biosystems allelic discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression adjusted for numerous breast cancer risk factors. Analysis was restricted to women with self-reported European descent. Prevalence of the Val/Val genotype was 5.6% in cases and 7.1% in controls. In comparison with the Ile/Ile genotype, the Ile/Val genotype was not significantly associated with breast cancer risk (OR 0.97, 95% CI 0.79 to 1.18), whereas the Val/Val genotype was associated with a reduced risk (OR 0.63, 95% CI 0.42 to 0.92). This inverse association seemed strongest in older women (OR 0.51, 95% CI 0.29 to 0.89 for women aged more than 55 years), women without a family history of breast cancer (OR 0.54, 95% CI 0.35 to 0.84), postmenopausal women with greater body mass index (OR 0.43, 95% CI 0.20 to 0.91 for a body mass index of 25.3 kg/m2 or more), and cases diagnosed with non-localized breast cancer (OR 0.49, 95% CI 0.26 to 0.90). Although results from our population-based case-control study show an inverse association between the HER2 Ile655Val polymorphism and risk of invasive breast cancer, most other studies of this single-nucleotide polymorphism suggest an overall null

  12. 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.

  13. Toll-like receptor 4 prompts human breast cancer cells invasiveness via lipopolysaccharide stimulation and is overexpressed in patients with lymph node metastasis.

    Directory of Open Access Journals (Sweden)

    Huan Yang

    Full Text Available Toll-like receptor (TLR4-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. This study investigated the expression and biological role of TLR4 in human breast cancer metastasis. MCF-7 and MDA-MB-231 are human breast cancer cell lines with low and high metastatic potential, respectively. Using lipopolysaccharide (LPS to stimulate MCF-7 and MDA-MB-231 cells, expression of TLR4 mRNA and protein increased compared with that in control cells. TLR4 activation notably up-regulated expression of matrix metalloproteinase (MMP-2, MMP-9 and vascular endothelial growth factor(VEGF mRNA and their secretion in the supernatants of both cell lines. LPS enhanced invasion of MDA-MB-231 cells by transwell assay and MCF-7 cells by wound healing assay. LPS triggered increased expression of TLR4 downstream signaling pathway protein myeloid differentiation factor 88(MyD88 and resulted in interleukin (IL-6 and IL-10 higher production by human breast cancer cells. Stimulation of TLR4 with LPS promoted tumorigenesis and formed metastatic lesions in liver of nude mice. Moreover, expression of TLR4 and MyD88 as well as invasiveness and migration of the cells could be blocked by TLR4 antagonist. Combined with clinicopathological parameters, TLR4 was overexpressed in human breast cancer tissue and correlated with lymph node metastasis. These findings indicated that TLR4 may participate in the progression and metastasis of human breast cancer and provide a new therapeutic target.

  14. Toll-like receptor 4 prompts human breast cancer cells invasiveness via lipopolysaccharide stimulation and is overexpressed in patients with lymph node metastasis.

    Science.gov (United States)

    Yang, Huan; Wang, Bo; Wang, Tao; Xu, Longjiang; He, Chunyan; Wen, Huiyan; Yan, Jie; Su, Honghong; Zhu, Xueming

    2014-01-01

    Toll-like receptor (TLR)4-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. This study investigated the expression and biological role of TLR4 in human breast cancer metastasis. MCF-7 and MDA-MB-231 are human breast cancer cell lines with low and high metastatic potential, respectively. Using lipopolysaccharide (LPS) to stimulate MCF-7 and MDA-MB-231 cells, expression of TLR4 mRNA and protein increased compared with that in control cells. TLR4 activation notably up-regulated expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor(VEGF) mRNA and their secretion in the supernatants of both cell lines. LPS enhanced invasion of MDA-MB-231 cells by transwell assay and MCF-7 cells by wound healing assay. LPS triggered increased expression of TLR4 downstream signaling pathway protein myeloid differentiation factor 88(MyD88) and resulted in interleukin (IL)-6 and IL-10 higher production by human breast cancer cells. Stimulation of TLR4 with LPS promoted tumorigenesis and formed metastatic lesions in liver of nude mice. Moreover, expression of TLR4 and MyD88 as well as invasiveness and migration of the cells could be blocked by TLR4 antagonist. Combined with clinicopathological parameters, TLR4 was overexpressed in human breast cancer tissue and correlated with lymph node metastasis. These findings indicated that TLR4 may participate in the progression and metastasis of human breast cancer and provide a new therapeutic target.

  15. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese;

    2012-01-01

    The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells...... become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors....... We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed...

  16. Elevated STAT3 Signaling-Mediated Upregulation of MMP-2/9 Confers Enhanced Invasion Ability in Multidrug-Resistant Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Fei Zhang

    2015-10-01

    Full Text Available The development of multidrug resistance greatly impedes effective cancer therapy. Recent advances in cancer research have demonstrated that acquisition of multidrug resistance by cancer cells is usually accompanied by enhanced cell invasiveness. Several lines of evidence indicated that cross activation of other signaling pathways during development of drug resistance may increase invasive potential of multidrug-resistant (MDR cancer cells. However, the accurate mechanism of this process is largely undefined. In this study, to better understand the associated molecular pathways responsible for cancer progression induced by drug resistance, a MDR human breast cancer cell line SK-BR-3/EPR with P-glycoprotein overexpression was established using stepwise long-term exposure to increasing concentration of epirubicin. The SK-BR-3/EPR cell line exhibited decreased cell proliferative activity, but enhanced cell invasive capacity. We showed that the expression of metastasis-related matrix metalloproteinase (MMP-2/9 was elevated in SK-BR-3/EPR cells. Moreover, SK-BR-3/EPR cells showed elevated activation of STAT3. Activation of STAT3 signaling is responsible for enhanced invasiveness of SK-BR-3/EPR cells through upregulation of MMP-2/9. STAT3 is a well-known oncogene and is frequently implicated in tumorigenesis and chemotherapeutic resistance. Our findings augment insight into the mechanism underlying the functional association between MDR and cancer invasiveness.

  17. Downregulation of COX-2 and CYP 4A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis resistance, migration and invasion.

    Science.gov (United States)

    Zheng, Hao; Li, Ying; Wang, Yuzhong; Zhao, Haixia; Zhang, Jing; Chai, Hongyan; Tang, Tian; Yue, Jiang; Guo, Austin M; Yang, Jing

    2014-10-01

    Flavonoids exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Anoikis resistance occurs at multiple key stages of the metastatic cascade. Here, we demonstrate that isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, inhibits human breast cancer metastasis by preventing anoikis resistance, migration and invasion through downregulating cyclooxygenase (COX)-2 and cytochrome P450 (CYP) 4A signaling. ISL induced anoikis in MDA-MB-231 and BT-549 human breast cancer cells as evidenced by flow cytometry and the detection of caspase cleavage. Moreover, ISL inhibited the mRNA expression of phospholipase A2, COX-2 and CYP 4A and decreased the secretion of prostaglandin E2 (PGE2) and 20-hydroxyeicosatetraenoic acid (20-HETE) in detached MDA-MB-231 cells. In addition, it decreased the levels of phospho-PI3K (Tyr(458)), phospho-PDK (Ser(241)) and phospho-Akt (Thr(308)). Conversely, the exogenous addition of PGE2, WIT003 (a 20-HETE analog) and an EP4 agonist (CAY10580) or overexpression of constitutively active Akt reversed ISL-induced anoikis. ISL exerted the in vitro anti-migratory and anti-invasive activities, whereas the addition of PGE2, WIT003 and CAY10580 or overexpression of constitutively active Akt reversed the in vitro anti-migratory and anti-invasive activities of ISL in MDA-MB-231 cells. Notably, ISL inhibited the in vivo lung metastasis of MDA-MB-231 cells, together with decreased intratumoral levels of PGE2, 20-HETE and phospho-Akt (Thr(308)). In conclusion, ISL inhibits breast cancer metastasis by preventing anoikis resistance, migration and invasion via downregulating COX-2 and CYP 4A signaling. It suggests that ISL could be a promising multi-target agent for preventing breast cancer metastasis, and anoikis could represent a novel mechanism through which flavonoids may exert the anti-metastatic activities.

  18. Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer

    International Nuclear Information System (INIS)

    Purpose: To convene a multidisciplinary panel of breast experts to examine the relationship between margin width and ipsilateral breast tumor recurrence (IBTR) and develop a guideline for defining adequate margins in the setting of breast conserving surgery and adjuvant radiation therapy. Methods and Materials: A multidisciplinary consensus panel used a meta-analysis of margin width and IBTR from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. Results: Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a 2-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. Conclusions: The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs

  19. Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Moran, Meena S. [Department of Therapeutic Radiology, Yale School of Medicine, Yale University, New Haven, Connecticut (United States); Schnitt, Stuart J. [Department of Pathology, Harvard Medical School, Boston, Massachusetts (United States); Giuliano, Armando E. [Department of Surgery, Cedars Sinai Medical Center, Los Angeles, California (United States); Harris, Jay R. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Khan, Seema A. [Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (United States); Horton, Janet [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Klimberg, Suzanne [Department of Surgery, University of Arkansas for Medical Sciences, Fayetteville, Arkansas (United States); Chavez-MacGregor, Mariana [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Freedman, Gary [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (United States); Houssami, Nehmat [School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales (Australia); Johnson, Peggy L. [Advocate in Science, Susan G. Komen, Wichita, Kansas (United States); Morrow, Monica, E-mail: morrowm@mskcc.org [Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-03-01

    Purpose: To convene a multidisciplinary panel of breast experts to examine the relationship between margin width and ipsilateral breast tumor recurrence (IBTR) and develop a guideline for defining adequate margins in the setting of breast conserving surgery and adjuvant radiation therapy. Methods and Materials: A multidisciplinary consensus panel used a meta-analysis of margin width and IBTR from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. Results: Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a 2-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. Conclusions: The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

  20. High levels of γ-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer

    International Nuclear Information System (INIS)

    Previously, we performed analysis of gene expression in 46 axillary lymph node negative tumors and identified molecular gene signatures that resulted in different clinical outcomes. The aim of this study was to determine the correlation of γ-glutamyl hydrolase (GGH), fatty acid amide hydrolase (FAAH), Pirin (PIR) and TAF5-like RNA polymerase II, p300/CBP-associated factor (PCAF)-associated factor, 65 kDa (TAF5L), selected from identified gene signatures, with clinical outcomes as well as classical clinicopathological characteristics in primary invasive breast cancer patients. The protein levels of GGH, FAAH, PIR and TAF5L were assessed by immunohistochemistry (IHC) on a panel of 80 primary invasive breast tumors. Quantitative real-time PCR (qRT-PCR) and western blot analysis were performed to verify the expression levels of the candidate biomarkers. Patient disease-specific survival (DSS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. The prognostic biomarkers were identified by univariate analysis with a log-rank test and by multivariate analysis with Cox proportional hazards regression models. The GGH and FAAH protein levels were significantly up-regulated in invasive breast cancer tumors compared with adjacent non-cancerous tissues. Furthermore, the protein levels of GGH and FAAH were significantly correlated in tumor tissues. Tumoral GGH protein expression was significantly correlated with shorter DSS and RFS. Furthermore, the protein expression of GGH was positively correlated with undifferentiated tumors (BRE grade III) and ER/PR expressing tumors. Multivariate regression analysis showed that only GGH protein expression independently predicts DSS. No such correlations were found for FAAH, PIR and TAF5L protein expression. However, elevated protein levels of FAAH were positively associated with high number of lymph node involvement and upregulated levels of PIR were positively related with lymph node metastasis. The TAF5L was

  1. Dioxin emissions from a municipal solid waste incinerator and risk of invasive breast cancer: a population-based case-control study with GIS-derived exposure

    Directory of Open Access Journals (Sweden)

    Challier Bruno

    2008-01-01

    Full Text Available Abstract Background To date, few epidemiologic studies have examined the relationship between environmental PCDD/F exposure and breast cancer in human populations. Dioxin emissions from municipal solid waste incinerators (MSWIs are one of the major sources of environmental dioxins and are therefore an exposure source of public concern. The purpose of this study was to examine the association between dioxins emitted from a polluting MSWI and invasive breast cancer risk among women residing in the area under direct influence of the facility. Methods We compared 434 incident cases of invasive breast cancer diagnosed between 1996 and 2002, and 2170 controls randomly selected from the 1999 population census. A validated dispersion model was used as a proxy for dioxin exposure, yielding four exposure categories. The latter were linked to individual places of residence, using Geographic Information System technology. Results The age distribution at diagnosis for all cases combined showed a bimodal pattern with incidence peaks near 50 and 70 years old. This prompted us to run models separately for women aged 20–59 years, and women aged 60 years or older. Among women younger than 60 years old, no increased or decreased risk was found for any dioxin exposure category. Conversely, women over 60 years old living in the highest exposed zone were 0.31 time less likely (95% confidence interval, 0.08–0.89 to develop invasive breast cancer. Conclusion Before speculating that this decreased risk reflects a dioxin anti-estrogenic activity with greater effect on late-onset acquired breast cancer, some residual confounding must be envisaged.

  2. Prognostic Value of Primary Tumor Uptake on F 18 FDG PET/CT in Patients with Invasive Ductal Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Song, Bong Il; Hong, Chae Moon; Lee, Hong Je; Kang, Sungmin; Jeong, Shin Young; Kim, Hae Won; Chae, Yee Soo; Park, Ji Young; Lee, Sang Woo; Ahn, Byeong Cheol; Lee, Jaetae [Kyungpook National Univ. Hospital, Daegu (Korea, Republic of)

    2011-06-15

    To determine the prognostic implications of pretreatment F 18 FDG PET/CT in patients with invasive ductal breast cancer (IDC), we evaluated the relationship between FDG uptake of the primary tumor and known prognostic parameters of breast cancer. Prognostic significance of tumoral FDG uptake for the prediction of progression free survival (PFS) was also assessed. Fifty five female patients with IDC who underwent pretreatment F 18 FDG PET/CT were enrolled. The maximum standardized uptake value of the primary tumor (pSUVmax) was compared with clinico pathological parameters including tumor size, grade, estrogen receptor (ER), Progesterone receptor (PR), human epidermal growth factor receptor2 (HER2), axillary lymph node (LN) metastasis, and stage. The prognostic value of pSUVmax for PFS was assessed using the Kaplan Meier method. A high pSUVmax was significantly related to a higher stage of tumor size (P<0.05), grade (P<0.001), and stage (P<0.001). pSUVmax was significantly higher in ER negative tumors (P<0.001), PR negative tumors (P<0.001), and positive LN metastasis (P<0.01), but not different according to HER2 status. pSUVmax was significantly higher in patients with progression compared to patients who were disease free (10.6{+-}5.1 vs. 4.7{+-}3.5, P<0.001). A receiver operating characteristic curve demonstrated a pSUVmax of 6.6 to be the optimal cutoff for predicting PFS (sensitivity; 86.7%, specificity; 82.5%). The patients with a high pSUVmax (more than 6.6) had significantly shorter PFS compared to patients with a low pSUVmax (P<0.0001). pSUVmax on pretreatment F 18 FDG PET/CT could be used as a good surrogate marker for the prediction of progression in patients with IDC.

  3. Surgical Procedures for Breast Cancer - Mastectomy and Breast Conserving Therapy (Beyond the Basics)

    Science.gov (United States)

    ... performed BCT procedure in the United States and Canada. (See "Breast conserving therapy" .) Radiation therapy Invasive breast ... breast cancer The following organizations also provide reliable health ... and undertakings, oral or written, are hereby expressly superseded and canceled. ...

  4. Downregulation of COX-2 and CYP 4A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis resistance, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Hao; Li, Ying [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Wang, Yuzhong [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079 (China); Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Yue, Jiang [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Guo, Austin M., E-mail: Austin_Guo@nymc.edu [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China)

    2014-10-01

    Flavonoids exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Anoikis resistance occurs at multiple key stages of the metastatic cascade. Here, we demonstrate that isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, inhibits human breast cancer metastasis by preventing anoikis resistance, migration and invasion through downregulating cyclooxygenase (COX)-2 and cytochrome P450 (CYP) 4A signaling. ISL induced anoikis in MDA-MB-231 and BT-549 human breast cancer cells as evidenced by flow cytometry and the detection of caspase cleavage. Moreover, ISL inhibited the mRNA expression of phospholipase A2, COX-2 and CYP 4A and decreased the secretion of prostaglandin E{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE) in detached MDA-MB-231 cells. In addition, it decreased the levels of phospho-PI3K (Tyr{sup 458}), phospho-PDK (Ser{sup 241}) and phospho-Akt (Thr{sup 308}). Conversely, the exogenous addition of PGE{sub 2}, WIT003 (a 20-HETE analog) and an EP4 agonist (CAY10580) or overexpression of constitutively active Akt reversed ISL-induced anoikis. ISL exerted the in vitro anti-migratory and anti-invasive activities, whereas the addition of PGE{sub 2}, WIT003 and CAY10580 or overexpression of constitutively active Akt reversed the in vitro anti-migratory and anti-invasive activities of ISL in MDA-MB-231 cells. Notably, ISL inhibited the in vivo lung metastasis of MDA-MB-231 cells, together with decreased intratumoral levels of PGE{sub 2}, 20-HETE and phospho-Akt (Thr{sup 308}). In conclusion, ISL inhibits breast cancer metastasis by preventing anoikis resistance, migration and invasion via downregulating COX-2 and CYP 4A signaling. It suggests that ISL could be a promising multi-target agent for preventing breast cancer metastasis, and anoikis could represent a novel mechanism through which flavonoids may exert the anti-metastatic activities. - Highlights: • Isoliquiritigenin induces anoikis and suppresses

  5. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Bostanci, Zeynep, E-mail: zbostanci@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Alam, Samina, E-mail: sra116@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Soybel, David I., E-mail: dsoybel@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States); Kelleher, Shannon L., E-mail: slk39@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States)

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  6. 17β-estradiol promotes the invasion and migration of nuclear estrogen receptor-negative breast cancer cells through cross-talk between GPER1 and CXCR1.

    Science.gov (United States)

    Jiang, Qi-Feng; Wu, Ting-Ting; Yang, Jun-Yan; Dong, Chao-Ran; Wang, Ni; Liu, Xiao-Hua; Liu, Zhi-Min

    2013-11-01

    G protein-coupled estrogen receptor 1 (GPER1) is widely expressed in human breast cancers correlating with increased tumor size and malignancy. Although estrogen signaling via GPER1 was extensively studied in recent years, the underlying molecular mechanism of GPER1-associated metastasis of breast cancer still remains unclear. In this study, the main aims were focused on the potential role of GPER1 in regulating migration and invasion of nuclear estrogen receptor (ER)-negative breast cancer cells upon 17β-estradiol (E2) stimulation and the involved signaling pathway. Key events in estrogen signaling were chosen for our studies, such as the activation of ERK and AKT, nuclear translocation of NF-κB and secretion of Interleukin-8 (IL-8). The migration and invasion activities upon E2 stimulation were also examined in ER-negative SKBR3 and BT-20 breast cancer cells. Compared with ER-positive MCF-7 breast cancer cells, both SKBR3 and BT-20 cells had very similar expression of GPER1, but relatively high expression of CXC receptor-1 (CXCR1), which is considered as an active regulator for cancer metastasis upon binding IL-8. Results showed that E2 facilitated the activation of ERK, AKT and NF-κB, which could be significantly attenuated by GPER1 blockage or knock-down in both SKBR3 and BT-20 cells. Moreover, increased secretion of IL-8 induced by E2 was also inhibited either by specific inhibitors for GPER1, ERK, AKT, and NF-κB, or by knock-down for GPER1. Furthermore, E2 could activate the migration and invasion of both SKBR3 and BT-20 cells, which in turn could also be inhibited by blocking GPER1, ERK, AKT, NF-κB, and CXCR1, respectively, or knock-down for GPER1 and CXCR1. In conclusion, we demonstrated that estrogen signaling via GPER1 associated with the metastasis of breast cancer, which might be through GPER1/ERK&AKT/NF-κB/IL-8/CXCR1 cascade. The cross-talk between GPER1 and CXCR1 could be another potential target for the therapy of metastatic breast cancer.

  7. Nuclear β-catenin and CD44 upregulation characterize invasive cell populations in non-aggressive MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    In breast cancer cells, the metastatic cell state is strongly correlated to epithelial-to-mesenchymal transition (EMT) and the CD44+/CD24- stem cell phenotype. However, the MCF-7 cell line, which has a luminal epithelial-like phenotype and lacks a CD44+/CD24- subpopulation, has rare cell populations with higher Matrigel invasive ability. Thus, what are the potentially important differences between invasive and non-invasive breast cancer cells, and are the differences related to EMT or CD44/CD24 expression? Throughout the sequential selection process using Matrigel, we obtained MCF-7-14 cells of opposite migratory and invasive capabilities from MCF-7 cells. Comparative analysis of epithelial and mesenchymal marker expression was performed between parental MCF-7, selected MCF-7-14, and aggressive mesenchymal MDA-MB-231 cells. Furthermore, using microarray expression profiles of these cells, we selected differentially expressed genes for their invasive potential, and performed pathway and network analysis to identify a set of interesting genes, which were evaluated by RT-PCR, flow cytometry or function-blocking antibody treatment. MCF-7-14 cells had enhanced migratory and invasive ability compared with MCF-7 cells. Although MCF-7-14 cells, similar to MCF-7 cells, expressed E-cadherin but neither vimentin nor fibronectin, β-catenin was expressed not only on the cell membrane but also in the nucleus. Furthermore, using gene expression profiles of MCF-7, MCF-7-14 and MDA-MB-231 cells, we demonstrated that MCF-7-14 cells have alterations in signaling pathways regulating cell migration and identified a set of genes (PIK3R1, SOCS2, BMP7, CD44 and CD24). Interestingly, MCF-7-14 and its invasive clone CL6 cells displayed increased CD44 expression and downregulated CD24 expression compared with MCF-7 cells. Anti-CD44 antibody treatment significantly decreased cell migration and invasion in both MCF-7-14 and MCF-7-14 CL6 cells as well as MDA-MB-231 cells. MCF-7-14 cells are a

  8. Breast cancer surveillance.

    Science.gov (United States)

    Rachetta, Eleonora; Osano, Silvia; Astegiano, Francesco; Martincich, Laura

    2016-10-01

    Since several studies have demonstrated the inadequate diagnostic performance of mammography in high risk women, over the past two decades, different breast imaging tests have been evaluated as additional diagnostic methods to mammography, and the most relevant ones are the techniques that do not imply the use of X-rays, considering the young age of these patients and the higher radio-sensitivity. Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has risen growing interest not only because of the absence of use of X-rays, but also because it provides morpho-functional features, which may depict biological characteristics of breast tissues, including invasive and in situ cancers. Different multicenter non-randomized prospective studies aimed to evaluate breast DCE-MRI as an integral part of surveillance programs, agreed about the evidence that in high risk women screening with DCE-MRI is more effective than either mammography and/or ultrasound. Moreover, this modality leads to the identifications of cancers at a more favorable stage, allowing a real advantage in terms of tumor size and nodal involvement. The medical community is evaluating to suggest DCE-MRI alone as screening modality in high-risk women, as it was reported that in these cases the sensitivity of MRI plus conventional imaging was not significantly higher than that of MRI alone. Breast MRI is now recommended as part of screening program for high risk women by both European and American guidelines. PMID:26924173

  9. Effect of Melatonin in Epithelial Mesenchymal Transition Markers and Invasive Properties of Breast Cancer Stem Cells of Canine and Human Cell Lines.

    Science.gov (United States)

    Gonçalves, Naiane do Nascimento; Colombo, Jucimara; Lopes, Juliana Ramos; Gelaleti, Gabriela Bottaro; Moschetta, Marina Gobbe; Sonehara, Nathália Martins; Hellmén, Eva; Zanon, Caroline de Freitas; Oliani, Sônia Maria; Zuccari, Debora Aparecida Pires de Campos

    2016-01-01

    Cancer stem cells (CSCs) have been associated with metastasis and therapeutic resistance and can be generated via epithelial mesenchymal transition (EMT). Some studies suggest that the hormone melatonin acts in CSCs and may participate in the inhibition of the EMT. The objectives of this study were to evaluate the formation of mammospheres from the canine and human breast cancer cell lines, CMT-U229 and MCF-7, and the effects of melatonin treatment on the modulation of stem cell and EMT molecular markers: OCT4, E-cadherin, N-cadherin and vimentin, as well as on cell viability and invasiveness of the cells from mammospheres. The CMT-U229 and MCF-7 cell lines were subjected to three-dimensional culture in special medium for stem cells. The phenotype of mammospheres was first evaluated by flow cytometry (CD44(+)/CD24(low/-) marking). Cell viability was measured by MTT colorimetric assay and the expression of the proteins OCT4, E-cadherin, N-cadherin and vimentin was evaluated by immunofluorescence and quantified by optical densitometry. The analysis of cell migration and invasion was performed in Boyden Chamber. Flow cytometry proved the stem cell phenotype with CD44(+)/CD24(low/-) positive marking for both cell lines. Cell viability of CMT-U229 and MCF-7 cells was reduced after treatment with 1mM melatonin for 24 h (Pmelatonin for 24 hours. Moreover, treatment with melatonin was able to reduce cell migration and invasion in both cell lines when compared to control group (Pmelatonin shows an inhibitory role in the viability and invasiveness of breast cancer mammospheres as well as in modulating the expression of proteins related to EMT in breast CSCs, suggesting its potential anti-metastatic role in canine and human breast cancer cell lines. PMID:26934679

  10. Pyruvate Carboxylase Is Up-Regulated in Breast Cancer and Essential to Support Growth and Invasion of MDA-MB-231 Cells.

    Directory of Open Access Journals (Sweden)

    Phatchariya Phannasil

    Full Text Available Pyruvate carboxylase (PC is an anaplerotic enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate, which is crucial for replenishing tricarboxylic acid cycle intermediates when they are used for biosynthetic purposes. We examined the expression of PC by immunohistochemistry of paraffin-embedded breast tissue sections of 57 breast cancer patients with different stages of cancer progression. PC was expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. We also found statistical association between the levels of PC expression and tumor size and tumor stage (P < 0.05. The involvement of PC with these two parameters was further studied in four breast cancer cell lines with different metastatic potentials; i.e., MCF-7, SKBR3 (low metastasis, MDA-MB-435 (moderate metastasis and MDA-MB-231 (high metastasis. The abundance of both PC mRNA and protein in MDA-MB-231 and MDA-MB-435 cells was 2-3-fold higher than that in MCF-7 and SKBR3 cells. siRNA-mediated knockdown of PC expression in MDA-MB-231 and MDA-MB-435 cells resulted in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of PC in MCF-7 cells resulted in a 2-fold increase in their proliferation rate, migration and invasion abilities. Taken together the above results suggest that anaplerosis via PC is important for breast cancer cells to support their growth and motility.

  11. Increased risk for invasive breast cancer associated with hormonal therapy: a nation-wide random sample of 65,723 women followed from 1997 to 2008.

    Directory of Open Access Journals (Sweden)

    Jung-Nien Lai

    Full Text Available BACKGROUND: Hormonal therapy (HT either estrogen alone (E-alone or estrogen plus progesterone (E+P appears to increase the risk for breast cancer in Western countries. However, limited information is available on the association between HT and breast cancer in Asian women characterized mainly by dietary phytoestrogens intake and low prevalence of contraceptive pills prescription. METHODOLOGY: A total of 65,723 women (20-79 years of age without cancer or the use of Chinese herbal products were recruited from a nation-wide one-million representative sample of the National Health Insurance of Taiwan and followed from 1997 to 2008. Seven hundred and eighty incidents of invasive breast cancer were diagnosed. Using a reference group that comprised 40,052 women who had never received a hormone prescription, Cox proportional hazard models were constructed to determine the hazard ratios for receiving different types of HT and the occurrence of breast cancer. CONCLUSIONS: 5,156 (20% women ever used E+P, 2,798 (10.8% ever used E-alone, and 17,717 (69% ever used other preparation types. The Cox model revealed adjusted hazard ratios (HRs of 2.05 (95% CI 1.37-3.07 for current users of E-alone and 8.65 (95% CI 5.45-13.70 for current users of E+P. Using women who had ceased to take hormonal medication for 6 years or more as the reference group, the adjusted HRs were significantly elevated and greater than current users and women who had discontinued hormonal medication for less than 6 years. Current users of either E-alone or E+P have an increased risk for invasive breast cancer in Taiwan, and precautions should be taken when such agents are prescribed.

  12. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

    International Nuclear Information System (INIS)

    Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In vitro, IGFBP-3's mechanisms of action may involve cell membrane binding and nuclear translocation. To evaluate tumour-specific IGFBP-3 expression and its subcellular localisation, this study examined immunohistochemical IGFBP-3 expression in a series of invasive ductal breast cancers (IDCs) with synchronous ductal carcinomas in situ (DCIS) in relation to clinicopathological variables and patient outcome. Immunohistochemical expression of IGFBP-3 was evaluated with the sheep polyclonal antiserum (developed in house) with staining performed as described previously. IGFBP-3 was evaluable in 101 patients with a variable pattern of cytoplasmic expression (positivity of 1+/2+ score) in 85% of invasive and 90% of DCIS components. Strong (2+) IGFBP-3 expression was evident in 32 IDCs and 40 cases of DCIS. A minority of invasive tumours (15%) and DCIS (10%) lacked IGFBP-3 expression. Nuclear IGFBP-3 expression was not detectable in either invasive cancers or DCIS, with a consistent similarity in IGFBP-3 immunoreactivity in IDCs and DCIS. Positive IGFBP-3 expression showed a possible trend in association with increased proliferation (P = 0.096), oestrogen receptor (ER) negativity (P = 0.06) and HER-2 overexpression (P = 0.065) in invasive tumours and a strong association with ER negativity (P = 0.037) in DCIS. Although IGFBP-3 expression was not an independent prognosticator, IGFBP-3-positive breast cancers may have shorter disease-free and overall survivals, although these did not reach

  13. Breast cancer in Kumasi, Ghana

    International Nuclear Information System (INIS)

    Breast cancer is the leading cause of cancer deaths in Ghanaian women.To describes the characteristics of breast cancer patients attending the Komfo Anokye Teaching Hospital in Kumasi, Ghana.The study was conducted at the Komfo Anokye Teaching Hospital. Between July 1st 2004 and June 30th 2009 patients presenting with breast lumps were assessed by clinical examination, imaging studies and pathological examination. Relevant clinical and pathological were recorded prospectively data on all patients with microscopically proven breast cancer. The cancers were graded according to the modified Bloom-Richardson system. Tissue immunoperoxidase stains for oestrogen, progesterone receptors and c-erb2 oncogene were performed with commercially prepared antigens and reagents.Nineteen thousand four hundred and twenty – three (19,423) patients were seen during the study period. There were 330 (1.7%) patients with histologically proven breast cancer. The mean age was 49.1 years. A palpable breast lump was detected in 248 patients (75.2%). Two hundred and eighty –one patients (85.2%) presented with Stages III and IV , 271 (82.1%) invasive and 230 ( 85.2%) high grade carcinomas. Oestrogen and progesterone receptors were positive in 32 and 9 cases respectively. Her2 protein was positive in 11 cases. In Kumasi, as in other parts of Ghana, breast cancer affects mostly young pre-menopausal who present with advanced disease. The cancers have unfavourable prognostic features and are unlikely to respond to hormonal therapy. (au)

  14. Virtual Touch tissue quantification cannot assess breast cancer lesions except for ductal carcinomas in situ and small invasive cancers: a retrospective study

    OpenAIRE

    Tada, Keiichiro; Nishioka, Kotoe; Kikuchi, Yasuko; Niwa, Takayoshi; Seto, Yasuyuki

    2015-01-01

    Background Virtual Touch tissue quantification (VTTQ) is a promising new technology that quantitatively determines the stiffness of tissue. However, the clinical impact of this device on the assessment of breast cancer is unclear. Methods This study aimed to review the ultrasound records of patients with breast lesions where VTTQ was used to assess 123 normal breast tissues, 18 benign tumors, and 117 histopathologically confirmed breast cancers in a total of 129 patients. To determine the VTT...

  15. Occult Invasive Lobular Carcinoma of Breast Detected by Stomach Metastasis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    KIm, So Jung; Jung, Hae Kyoung; Ko, Kyung Hee; Yoon, Jung Hyun [Dept. of Radiology, Bundang CHA general Hospital, CHA University College of Medicine, Seongnam (Korea, Republic of)

    2012-02-15

    Gastric metastasis from primary breast cancer is a rare phenomenon that is more prevalent in the invasive lobular type of breast cancer. We describe a very rare case of occult invasive lobular cancer of the breast detected by the initial presentation of gastric metastasis in a patient without a history of breast cancer. A 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) which showed increased FDG uptake in the stomach, abdominal mesentery and the right breast, and played pivotal roles in the detection of occult primary breast cancer and a diagnosis of gastric metastasis as an ancillary method for obtaining histological results and immunohistochemical stains.

  16. Occult Invasive Lobular Carcinoma of Breast Detected by Stomach Metastasis: A Case Report

    International Nuclear Information System (INIS)

    Gastric metastasis from primary breast cancer is a rare phenomenon that is more prevalent in the invasive lobular type of breast cancer. We describe a very rare case of occult invasive lobular cancer of the breast detected by the initial presentation of gastric metastasis in a patient without a history of breast cancer. A 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) which showed increased FDG uptake in the stomach, abdominal mesentery and the right breast, and played pivotal roles in the detection of occult primary breast cancer and a diagnosis of gastric metastasis as an ancillary method for obtaining histological results and immunohistochemical stains.

  17. Breast Cancer Risk Assessment SAS Macro (Gail Model)

    Science.gov (United States)

    A SAS macro (commonly referred to as the Gail Model) that projects absolute risk of invasive breast cancer according to NCI’s Breast Cancer Risk Assessment Tool (BCRAT) algorithm for specified race/ethnic groups and age intervals.

  18. Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Jensen, Maj-Britt; Rank, Fritz;

    2009-01-01

    characteristics and therapy. All statistical tests were two-sided. RESULTS: Complete follow-up was achieved for 15,659 patients. The median estimated potential follow-up was 6.4 years for invasive disease-free interval and 7.7 years for overall survival. Invasive disease-free interval and overall survival were...

  19. Exogenous Expression of N-Cadherin in Breast Cancer Cells Induces Cell Migration, Invasion, and Metastasis

    OpenAIRE

    Hazan, Rachel B.; Phillips, Greg R.; Qiao, Rui Fang; Norton, Larry; Aaronson, Stuart A.

    2000-01-01

    E- and N-cadherin are calcium-dependent cell adhesion molecules that mediate cell–cell adhesion and also modulate cell migration and tumor invasiveness. The loss of E-cadherin–mediated adhesion has been shown to play an important role in the transition of epithelial tumors from a benign to an invasive state. However, recent evidence indicates that another member of the cadherin family, N-cadherin, is expressed in highly invasive tumor cell lines that lacked E-cadherin expression. These findin...

  20. 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 ...

  1. 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. ...

  2. Role of the Copper(II) Complex Cu[15]pyN5 in Intracellular ROS and Breast Cancer Cell Motility and Invasion.

    Science.gov (United States)

    Fernandes, Ana S; Flórido, Ana; Saraiva, Nuno; Cerqueira, Sara; Ramalhete, Sérgio; Cipriano, Madalena; Cabral, Maria Fátima; Miranda, Joana P; Castro, Matilde; Costa, Judite; Oliveira, Nuno G

    2015-10-01

    Multiple mechanisms related to metastases undergo redox regulation. Cu[15]pyN5 is a redox-active copper(II) complex previously studied as a chemotherapy sensitizer in mammary cells. The effects of a cotreatment with Cu[15]pyN5 and doxorubicin (dox) were evaluated in two human breast cancer cell lines: MCF7 (low aggressiveness) and MDA-MB-231 (highly aggressive). Cu[15]pyN5 decreased MCF7-directed cell migration. In addition, a cotreatment with dox and Cu[15]pyN5 reduced the proteolytic invasion of MDA-MB-231 cells. Cell detachment was not affected by exposure to these agents. Cu[15]pyN5 and dox significantly increased intracellular ROS in both cell lines. This increase could be at least partially due to H2 O2 accumulation. The combination of Cu[15]pyN5 with dox may be beneficial in breast cancer treatment as it could help reduce cancer cell migration and invasion. Moreover, the ligand [15]pyN5 has a high affinity for copper(II) and displays potential anti-angiogenic properties. Overall, we present a potential drug that might arrest the progression of breast cancer by different and complementary mechanisms.

  3. Research advances of MMPs and invasion and metastasis of breast cancer%MMPs与乳腺癌侵袭转移研究的现状

    Institute of Scientific and Technical Information of China (English)

    邓晓莉; 张文海

    2011-01-01

    目的:探讨基质金属蛋白酶(MMPs)在肿瘤侵袭和转移过程中的作用机制及其在乳腺癌临床诊断与治疗中的应用价值.方法:以乳腺癌、侵袭转移和MMPs为关键词,检索近几年PubMed全文.纳入标准:1)肿瘤转移机制的最新研究进展;2)MMPs结构及生物学特性的研究;3)与乳腺癌相关的MMPs的最新研究进展.根据纳入标准,最后纳入分析28篇文献.结果:MMPs不仅降解细胞外基质,还促进或抑制肿瘤血管的新生,以及诱导肿瘤细胞免疫耐受.MMPs在乳腺癌中的特异性高表达,为乳腺癌的早期诊断与治疗提供了一种新思路.结论:MMPs与乳腺癌侵袭转移关系尤为密切,将有望成为乳腺癌临床研究中重要的诊断及判断预后的指标.%OBJECTIVE, To investigate the matrix metallopro-teinases (MMPs) in tumor invasion and metastasis and its mechanism in breast cancer diagnosis and treatment of value. METHODS: Breast cancer, invasion, metastasis, and MMPs as key words, full text were searched in PubMed. Inclusion criteria: 1) tumor metastasis of the latest research advances; 2) MMPs structure and biological characteristics; 3) MMPs associated with breasj cancer latest research progress. Aceorading to the inclusion criteria, foreign documents were selected, 28 articles included in the analysis. RESULTS: MMPs not only degrade the extracellular matrix, but also promote or inhibit tumor angiogenesis and immune tolerance induced by tumor cells. Its high specificity in the expression of breast cancer for early diagnosis and treatment of breast cancer provides a new idea. CONCLUSION: MMPs is closely associated with invasion and metastasis of breast cancer, and expected to become an important clinical research in breast cancer diagnostic and prognostic indicator.

  4. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro.

    Science.gov (United States)

    Aumsuwan, Pranapda; Khan, Shabana I; Khan, Ikhlas A; Ali, Zulfiqar; Avula, Bharathi; Walker, Larry A; Shariat-Madar, Zia; Helferich, William G; Katzenellenbogen, Benita S; Dasmahapatra, Asok K

    2016-02-01

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to find out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast cancer cells. MCF-7 and MDA-MB-231 cells were treated in the absence/presence of various concentrations of DS and subjected to gene analysis by RT-qPCR, immunoblotting, and immunocytochemistry. We determined the ability of MDA-MB-231 cells to migrate into wound area and examined the effects of DS on cellular invasion using invasion assay. DS reduced cell viability of both cell lines in a concentration and time-dependent manner. GATA3 expression was enhanced by DS (5.76 μM) in MDA-MB-231 cells. DS (5.76 μM)-treated MDA-MB-231 cells exhibited the morphological characteristic of epithelial-like cells; mRNA expression of DNMT3A, TET2, TET3, ZFPM2 and E-cad were increased while TET1, VIM and MMP9 were decreased. Cellular invasion of MDA-MB-231 was reduced by 65 ± 5% in the presence of 5.76 μM DS. Our data suggested that DS-mediated pathway could promote GATA3 expression at transcription and translation levels. We propose that DS has potential to be used as an anti-invasive agent in breast cancer. PMID:26682631

  5. Standardized and reproducible methodology for the comprehensive and systematic assessment of surgical resection margins during breast-conserving surgery for invasive breast cancer

    International Nuclear Information System (INIS)

    The primary goal of breast-conserving surgery (BCS) is to completely excise the tumor and achieve 'adequate' or 'negative' surgical resection margins while maintaining an acceptable level of postoperative cosmetic outcome. Nevertheless, precise determination of the adequacy of BCS has long been debated. In this regard, the aim of the current paper was to describe a standardized and reproducible methodology for comprehensive and systematic assessment of surgical resection margins during BCS. Retrospective analysis of 204 BCS procedures performed for invasive breast cancer from August 2003 to June 2007, in which patients underwent a standard BCS resection and systematic sampling of nine standardized re-resection margins (superior, superior-medial, superior-lateral, medial, lateral, inferior, inferior-medial, inferior-lateral, and deep-posterior). Multiple variables (including patient, tumor, specimen, and follow-up variables) were evaluated. 6.4% (13/204) of patients had positive BCS specimen margins (defined as tumor at inked edge of BCS specimen) and 4.4% (9/204) of patients had close margins (defined as tumor within 1 mm or less of inked edge but not at inked edge of BCS specimen). 11.8% (24/204) of patients had at least one re-resection margin containing additional disease, independent of the status of the BCS specimen margins. 7.1% (13/182) of patients with negative BCS specimen margins (defined as no tumor cells seen within 1 mm or less of inked edge of BCS specimen) had at least one re-resection margin containing additional disease. Thus, 54.2% (13/24) of patients with additional disease in a re-resection margin would not have been recognized by a standard BCS procedure alone (P < 0.001). The nine standardized resection margins represented only 26.8% of the volume of the BCS specimen and 32.6% of the surface area of the BCS specimen. Our methodology accurately assesses the adequacy of surgical resection margins for determination of which

  6. 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 ...

  7. Invasive lobular carcinoma: a rare presentation in the male breast.

    Science.gov (United States)

    Melo Abreu, Elisa; Pereira, Pedro; Marques, José Carlos; Esteves, Gonçalo

    2016-01-01

    Breast cancer in men is uncommon, accounting for ratio and familial history (BRCA 2 and 1). The authors present a case of a 52-year-old man with no relevant predisposing factors to breast cancer, who presented with a painless, firm nodule, fixed to the nipple on the left breast, associated with nipple retraction and ulceration, and fully characterised by mammogram and ultrasound. Histopathological and immunohistochemical analysis revealed the diagnosis of invasive lobular breast carcinoma and the patient underwent left radical mastectomy, followed by adjuvant chemotherapy, radiotherapy and hormonotherapy. A brief review of the literature is presented. PMID:27151060

  8. Local recurrence after breast-conserving therapy for invasive breast cancer: High incidence in young patients and association with poor survival

    International Nuclear Information System (INIS)

    Purpose: To study risk factors for local recurrence (LR) after breast-conserving therapy (BCT) for invasive breast cancer and, for patients with an LR, the mode of detection, location, treatment, influence of radiation therapy, and impact on survival. Methods and Materials: 1360 patients (median age 52 years; range 24-88) with a total of 1393 pT1-2 N0-1 tumors treated with BCT between 1980-1994 were studied (median follow-up 52 months). The adequacy of radiation treatment of the patients developing LR was studied in a quality control study. The impact of LR on overall survival and distant metastasis was studied in a Cox regression model with LR as a time-dependent covariate. Results: A total of 88 LR occurred with a 5- and 10-year LR risk of 8 and 12%. Age was the only significant risk factor. Compared to patients >65 years old, patients <45 years old and patients 45-65 years old had a relative risk (RR) of 4.09 and 2.41, respectively, of developing LR. Risk on LR was found to increase gradually with younger age. Radiation therapy was considered adequate and did not play a role in influencing the LR rate. Almost 65% of the LR were true or marginal recurrences. Of all LR, 80% appeared during the first 5 years and were detected with equal frequency by the patient herself, the physician, and annual mammography. LR was a major predictor for distant metastasis (RR: 4.90; 3.15-7.62) and death (RR: 4.29; 2.93-6.28). Conclusion: Young age is a major risk factor for LR and there is a significant gradual increase in LR with decreasing age. LR is associated with a higher risk of distant metastasis and death. Whether LR is the cause of or a marker for distant metastasis remains unresolved

  9. RECURRENCE PATTERN FOLLOWING BREAST - CONSERVING SURGERY FOR EARLY BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Govindaraj

    2015-08-01

    Full Text Available OBJECTIVE: To study the Local Recurrence and metastasis pattern after Breast - Conserving Surgery for early breast cancer. MATERIALS AND METHODS: From 2010 to 2014 in department of surgery in VIMS Bellary, 70 patients with stage I or II invasive breast carcinoma were treated with breast - conserving surgery, radiation and chemotherapy. In this study we investigated the prognostic value of clinical and pathological factors in early breast cancer patients treated with BCS. All of the surgeries were performed by a single surgical team. Recurrence and its risk factors were evaluated.

  10. Inhibition of breast cancer invasion by TIS21/BTG2/Pc3-Akt1-Sp1-Nox4 pathway targeting actin nucleators, mDia genes.

    Science.gov (United States)

    Choi, J-A; Jung, Y S; Kim, J Y; Kim, H M; Lim, I K

    2016-01-01

    The mammalian homolog of Drosophila diaphanous (mDia), actin nucleator, has been known to participate in the process of invasion and metastasis of cancer cells via regulating a number of actin-related biological processes. We have previously reported that tumor suppressor TIS21(/BTG2/Pc3) (TIS21) inhibits invadopodia formation by downregulating reactive oxygen species (ROS) in MDA-MB-231 cells. We herein report that TIS21(/BTG2/Pc3) downregulates diaphanous-related formin (DRF) expression via reducing NADPH oxidase 4 (Nox4)-derived ROS generation by Akt1 activation and subsequently impairs invasion activity of the highly invasive breast cancer cells. Knockdown of Akt1 by RNA interference recovered the TIS21(/BTG2/Pc3)-inhibited F-actin remodeling and ROS generation by recovering Nox4 expression. Furthermore, Sp1-mediated Nox4 transcription was downregulated by TIS21(/BTG2/Pc3)-Akt1 signals, leading to the inhibition of cancer cell invasion via F-actin remodeling by mDia genes. To our best knowledge, this is the first study to show that TIS21(/BTG2/Pc3)-Akt1 inhibited Sp1-Nox4-ROS cascade, subsequently reducing invasion activity via inhibition of mDia family genes.

  11. Aromatic-turmerone attenuates invasion and expression of MMP-9 and COX-2 through inhibition of NF-κB activation in TPA-induced breast cancer cells.

    Science.gov (United States)

    Park, Sun Young; Kim, Young Hun; Kim, YoungHee; Lee, Sang-Joon

    2012-12-01

    Recent evidence suggests that breast cancer is one of the most common forms of malignancy in females, and metastasis from the primary cancer site is the main cause of death. Aromatic (ar)-turmerone is present in Curcuma longa and is a common remedy and food. In the present study, we investigated the inhibitory effects of ar-turmerone on expression and enzymatic activity levels of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase (MMP)-9 and cyclooxygenaase-2 (COX-2) in breast cancer cells. Our data indicated that ar-turmerone treatment significantly inhibited enzymatic activity and expression of MMP-9 and COX-2 at non-cytotoxic concentrations. However, the expression of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, MMP-2, and COX-1 did not change upon ar-turmerone treatment. We found that ar-turmerone inhibited the activation of NF-κB, whereas it did not affect AP-1 activation. Moreover, The ChIP assay revealed that in vivo binding activities of NF-κB to the MMP-9 and COX-2 promoter were significantly inhibited by ar-turmerone. Our data showed that ar-turmerone reduced the phosphorylation of PI3K/Akt and ERK1/2 signaling, whereas it did not affect phosphorylation of JNK or p38 MAPK. Thus, transfection of breast cancer cells with PI3K/Akt and ERK1/2 siRNAs significantly decreased TPA-induced MMP-9 and COX-2 expression. These results suggest that ar-turmerone suppressed the TPA-induced up-regulation of MMP-9 and COX-2 expression by blocking NF-κB, PI3K/Akt, and ERK1/2 signaling in human breast cancer cells. Furthermore, ar-turmerone significantly inhibited TPA-induced invasion, migration, and colony formation in human breast cancer cells.

  12. Evaluation of the Ca 1 antibody in the diagnosis of invasive breast cancer.

    OpenAIRE

    Clough, D G; Coghill, G R; Holley, M. P.

    1984-01-01

    An evaluation of Ca 1 antibody staining was performed on paraffin sections from 136 breast lesions (64 benign and 72 malignant). Although cytoplasmic staining was encountered significantly more often in malignant lesions, the false negative rate was 6.9% and the false positive rate 56.2%. Benign lesions which showed positive staining included gynaecomastia, cystic mastopathy and fibroadenomata. Various other monoclonal antibodies showed staining similar to Ca 1 antibody. Ca 1 antibody was obs...

  13. The diagnosis and management of pre-invasive breast disease: Genetic alterations in pre-invasive lesions

    OpenAIRE

    Reis-Filho, Jorge S; Lakhani, Sunil R.

    2003-01-01

    The development of modern molecular genetic techniques has allowed breast cancer researchers to clarify the multistep model of breast carcinogenesis. Laser capture microdissection coupled with comparative genomic hybridisation and/or loss-of-heterozygosity methods have confirmed that many pre-invasive lesions of the breast harbour chromosomal abnormalities at loci known to be altered in invasive breast carcinomas. Current data do not provide strong evidence for ductal hyperplasia of usual typ...

  14. Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status

    International Nuclear Information System (INIS)

    Black women are more likely than white women to have an aggressive subtype of breast cancer that is associated with higher mortality and this may contribute to the observed black-white difference in mortality. However, few studies have investigated the black-white disparity in mortality risk stratified by breast cancer subtype, defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Furthermore, it is not known whether additional consideration of p53 protein status influences black-white differences in mortality risk observed when considering subtypes defined by ER, PR and HER2 status. Four biomarkers were assessed by immunohistochemistry in paraffin-embedded breast tumor tissue from 1,204 (523 black, 681 white) women with invasive breast cancer, aged 35–64 years at diagnosis, who accrued a median of 10 years’ follow-up. Multivariable Cox proportional hazards regression models were fit to assess subtype-specific black-white differences in mortality risk. No black-white differences in mortality risk were observed for women with triple negative (ER-negative [ER-], PR-, and HER2-) subtype. However, older (50–64 years) black women had greater overall mortality risk than older white women if they had been diagnosed with luminal A (ER-positive [ER+] or PR+ plus HER2-) breast cancer (all-cause hazard ratio, HR, 1.88; 95% confidence interval, CI, 1.18 to 2.99; breast cancer-specific HR, 1.51; 95% CI, 0.83 to 2.74). This black-white difference among older women was further confined to those with luminal A/p53- tumors (all-cause HR, 2.22; 95% CI, 1.30 to 3.79; breast cancer-specific HR, 1.89; 95% CI, 0.93 to 3.86). Tests for homogeneity of race-specific HRs comparing luminal A to triple negative subtype and luminal A/p53- to luminal A/p53+ subtype did not achieve statistical significance, although statistical power was limited. Our findings suggest that the subtype-specific black-white difference in

  15. 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 ...

  16. The lipid-reactive oxygen species phenotype of breast cancer. Raman spectroscopy and mapping, PCA and PLSDA for invasive ductal carcinoma and invasive lobular carcinoma. Molecular tumorigenic mechanisms beyond Warburg effect.

    Science.gov (United States)

    Surmacki, Jakub; Brozek-Pluska, Beata; Kordek, Radzislaw; Abramczyk, Halina

    2015-04-01

    Vibrational signatures of human breast tissue (invasive ductal carcinoma and invasive lobular carcinoma) were used to identify, characterize and discriminate structures in normal (noncancerous) and cancerous tissues by confocal Raman imaging, Raman spectroscopy and IR spectroscopy. The most important differences between normal and cancerous tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives. K-means clustering and basis analysis followed by PCA and PLSDA is employed to analyze Raman spectroscopic maps of human breast tissue and for a statistical analysis of the samples (82 patients, 164 samples). Raman maps successfully identify regions of carotenoids, fatty acids, and proteins. The intensities, frequencies and profiles of the average Raman spectra differentiate the biochemical composition of normal and cancerous tissues. The paper demonstrates that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The sensitivity and specificity obtained directly from PLSLD and cross validation are equal to 90.5% and 84.8% for calibration and 84.7% and 71.9% for cross-validation respectively.

  17. Immunostaining with D2–40 improves evaluation of lymphovascular invasion, but may not predict sentinel lymph node status in early breast cancer

    Directory of Open Access Journals (Sweden)

    Vassallo José

    2009-04-01

    Full Text Available Abstract Background Sentinel lymph node (SLN biopsy is a widely used diagnostic procedure in the management of early breast cancer. When SLN is free of metastasis, complete axillary dissection may be skipped for staging in clinically N0 patients, allowing a more conservative procedure. Histological tumor features that could reliably predict SLN status have not yet been established. Since the degree of tumor lymphangiogenesis and vascularization may theoretically be related to the risk of lymph node metastasis, we sought to evaluate the relationship between lymph vessel invasion (LVI, lymphatic microvascular density (LVD, microvascular density (MVD and VEGF-A expression, with SLN status and other known adverse clinical risk factors. Methods Protein expression of D2–40, CD34, and VEGF-A was assessed by immunohistochemistry on paraffin-embedded sections of primary breast cancer specimens from 92 patients submitted to SLN investigation. The presence of LVI, the highest number of micro vessels stained for D2–40 and CD34, and the protein expression of VEGF-A were compared to SLN status, clinicopathological features and risk groups. Results LVI was detected in higher ratios by immunostaining with D2–40 (p Conclusion Assessment of LVI in breast carcinoma may be significantly increased by immunostaining with D2–40, but the clinical relevance of altering the risk category using this parameter may not be advocated according to our results, neither can the use of LVI and LVD as predictors of SLN macrometastasis in early breast cancer.

  18. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    DEFF Research Database (Denmark)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos;

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast can...

  19. Using hair to screen for breast cancer

    Science.gov (United States)

    James, Veronica; Kearsley, John; Irving, Tom; Amemiya, Yoshiyuki; Cookson, David

    1999-03-01

    We have studied hair using fibre X-ray diffraction studies with synchrotron radiation and find that hair from breast-cancer patients has a different intermolecular structure to hair from healthy subjects. These changes are seen in all samples of scalp and pubic hair taken from women diagnosed with breast cancer. All the hair samples from women who tested positive for a mutation of the BRCA1 gene, which is associated with a higher risk of breast cancer, also show these changes. Because our results are so consistent, we propose that such hair analyses may be used as a simple, non-invasive screening method for breast cancer.

  20. The diagnosis and management of pre-invasive breast disease: Promise of new technologies in understanding pre-invasive breast lesions

    OpenAIRE

    Jeffrey, Stefanie S; Jonathan R Pollack

    2003-01-01

    Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-invasive breast lesions is discussed, including methods that facilitate their implementation. Data indicate that atypical ductal hyperplasia and ductal carcinoma in situ are precurs...

  1. p300 and p53 levels determine activation of HIF-1 downstream targets in invasive breast cancer

    NARCIS (Netherlands)

    Vleugel, M.M.; Shvarts, D.; Wall, E. van der; Diest, P.J. van

    2006-01-01

    In previous studies, we noted that overexpression of hypoxia-inducible factor (HIF)–1a in breast cancer, especially the diffuse form, does not always lead to functional activation of its downstream genes. Transcriptional activity of HIF-1 may be repressed by p53 through competition for transcription

  2. miR-564 acts as a dual inhibitor of PI3K and MAPK signaling networks and inhibits proliferation and invasion in breast cancer

    Science.gov (United States)

    Mutlu, Merve; Saatci, Özge; Ansari, Suhail A.; Yurdusev, Emre; Shehwana, Huma; Konu, Özlen; Raza, Umar; Şahin, Özgür

    2016-01-01

    Dysregulation of PI3K and MAPK pathways promotes uncontrolled cell proliferation, apoptotic inhibition and metastasis. Individual targeting of these pathways using kinase inhibitors has largely been insufficient due to the existence of cross-talks between these parallel cascades. MicroRNAs are small non-coding RNAs targeting several genes simultaneously and controlling cancer-related processes. To identify miRNAs repressing both PI3K and MAPK pathways in breast cancer, we re-analyzed our previous miRNA mimic screen data with reverse phase protein array (RPPA) output, and identified miR-564 inhibiting both PI3K and MAPK pathways causing markedly decreased cell proliferation through G1 arrest. Moreover, ectopic expression of miR-564 blocks epithelial-mesenchymal transition (EMT) and reduces migration and invasion of aggressive breast cancer cells. Mechanistically, miR-564 directly targets a network of genes comprising AKT2, GNA12, GYS1 and SRF, thereby facilitating simultaneous repression of PI3K and MAPK pathways. Notably, combinatorial knockdown of these target genes using a cocktail of siRNAs mimics the phenotypes exerted upon miR-564 expression. Importantly, high miR-564 expression or low expression of target genes in combination is significantly correlated with better distant relapse-free survival of patients. Overall, miR-564 is a potential dual inhibitor of PI3K and MAPK pathways, and may be an attractive target and prognostic marker for breast cancer. PMID:27600857

  3. miR-564 acts as a dual inhibitor of PI3K and MAPK signaling networks and inhibits proliferation and invasion in breast cancer

    Science.gov (United States)

    Mutlu, Merve; Saatci, Özge; Ansari, Suhail A.; Yurdusev, Emre; Shehwana, Huma; Konu, Özlen; Raza, Umar; Şahin, Özgür

    2016-09-01

    Dysregulation of PI3K and MAPK pathways promotes uncontrolled cell proliferation, apoptotic inhibition and metastasis. Individual targeting of these pathways using kinase inhibitors has largely been insufficient due to the existence of cross-talks between these parallel cascades. MicroRNAs are small non-coding RNAs targeting several genes simultaneously and controlling cancer-related processes. To identify miRNAs repressing both PI3K and MAPK pathways in breast cancer, we re-analyzed our previous miRNA mimic screen data with reverse phase protein array (RPPA) output, and identified miR-564 inhibiting both PI3K and MAPK pathways causing markedly decreased cell proliferation through G1 arrest. Moreover, ectopic expression of miR-564 blocks epithelial-mesenchymal transition (EMT) and reduces migration and invasion of aggressive breast cancer cells. Mechanistically, miR-564 directly targets a network of genes comprising AKT2, GNA12, GYS1 and SRF, thereby facilitating simultaneous repression of PI3K and MAPK pathways. Notably, combinatorial knockdown of these target genes using a cocktail of siRNAs mimics the phenotypes exerted upon miR-564 expression. Importantly, high miR-564 expression or low expression of target genes in combination is significantly correlated with better distant relapse-free survival of patients. Overall, miR-564 is a potential dual inhibitor of PI3K and MAPK pathways, and may be an attractive target and prognostic marker for breast cancer.

  4. Rack1 Mediates the Interaction of P-Glycoprotein with Anxa2 and Regulates Migration and Invasion of Multidrug-Resistant Breast Cancer Cells

    Science.gov (United States)

    Yang, Yi; Wu, Na; Wang, Zhiyong; Zhang, Fei; Tian, Ran; Ji, Wei; Ren, Xiubao; Niu, Ruifang

    2016-01-01

    The emergence of multidrug resistance is always associated with more rapid tumor recurrence and metastasis. P-glycoprotein (P-gp), which is a well-known multidrug-efflux transporter, confers enhanced invasion ability in drug-resistant cells. Previous studies have shown that P-gp probably exerts its tumor-promoting function via protein-protein interaction. These interactions were implicated in the activation of intracellular signal transduction. We previously showed that P-gp binds to Anxa2 and promotes the invasiveness of multidrug-resistant (MDR) breast cancer cells through regulation of Anxa2 phosphorylation. However, the accurate mechanism remains unclear. In the present study, a co-immunoprecipitation coupled with liquid chromatography tandem mass spectrometry-based interactomic approach was performed to screen P-gp binding proteins. We identified Rack1 as a novel P-gp binding protein. Knockdown of Rack1 significantly inhibited proliferation and invasion of MDR cancer cells. Mechanistic studies demonstrated that Rack1 functioned as a scaffold protein that mediated the binding of P-gp to Anxa2 and Src. We showed that Rack1 regulated P-gp activity, which was necessary for adriamycin-induced P-gp-mediated phosphorylation of Anxa2 and Erk1/2. Overall, the findings in this study augment novel insights to the understanding of the mechanism employed by P-gp for promoting migration and invasion of MDR cancer cells. PMID:27754360

  5. Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion

    OpenAIRE

    Rietkötter, Eva; Menck, Kerstin; Bleckmann, Annalen; Farhat, Katja; Schaffrinski, Meike; Schulz, Matthias; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias

    2013-01-01

    The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether this is due to direct toxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ ...

  6. [CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH INVASIVE BREAST CANCER--CROATIAN ONCOLOGY SOCIETY].

    Science.gov (United States)

    Šeparović, Robert; Ban, Marija; Silovska, Tajana; Oresković, Lidija Beketić; Soldić, Željko; Podolski, Paula; Pleština, Stjepko; Gugić, Damir; Petković, Marija; Jakić-Razumović, Jasminka; Vojnović, Zeljko; Miše, Branka Petrić; Tomić, Snježana; Stanec, Zdenko; Vrdoljak, Danko Velemir; Drinković, Ivan; Brkljačić, Boris; Mustać, Elvira; Utrobičić, Ivan; Vrdoljak, Eduard

    2015-01-01

    Breast cancer is the most common cancer in women. It can be diagnosed in early stage through screening, early detection and educational programs, and when diagnosed early it can be efficiently treated. Treatment modalities include surgery, chemotherapy, radiotherapy, hormonal therapy and targeted biologic therapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and monitoring of patients with breast cancer in the Republic of Croatia. PMID:26380471

  7. MiR-182 promotes proliferation and invasion and elevates the HIF-1α-VEGF-A axis in breast cancer cells by targeting FBXW7.

    Science.gov (United States)

    Chiang, Chi-Hsiang; Chu, Pei-Yi; Hou, Ming-Feng; Hung, Wen-Chun

    2016-01-01

    The feature of imperfect complementary effect of miRNAs to mRNAs implies that miRNAs may simultaneously target different mRNAs to affect multiple aspects of tumorigenesis. In our previous results, we demonstrated that miR-182 was over-expressed in breast cancer cell lines and clinical tumor tissues and its up-regulation increased tumorigenicity and invasiveness by repressing a tumor suppressor RECK. In this study, we showed that overexpression miR-182 regulated actin distribution and filopodia formation to increase invasiveness of breast cancer cells. In addition, miR-182 enhanced cell cycle progression and proliferation. We further identified the E3 ubiquitin-protein ligase FBXW7 as a target gene of miR-182. We also demonstrated that miR-182-overexpressing cells were highly sensitive to hypoxia. Under hypoxic condition, HIF-1α and VEGF-A proteins were significantly upregulated in these cells. In addition, the conditioned medium of miR-182-overexpressing cells contained more VEGF-A than the control cells and induced angiogenesis more efficiently in vitro. All these effects could be counteracted by ectopic expression of FBXW7 in cells or neutralization of VEGF-A in the conditioned media by specific antibody. Finally, our data showed that miR-182 expression was inversely correlated with FBXW7 in breast tumor tissues. In conclusion, our study explores a novel mechanism by which miR-182 elevates HIF-1α expression to promote breast cancer progression. PMID:27648365

  8. miRNAs as potential biomarkers in early breast cancer detection following mammography

    OpenAIRE

    Fu, Sidney W.; Lee, Woojin; Coffey, Caitrin; Lean, Alexa; Wu, Xiaoling; Tan, Xiaohui; Man, Yan-Gao; Brem, Rachel F.

    2016-01-01

    Breast cancer is the most common cancer among American women, except for skin cancers. About 12 % women in the United States will develop invasive breast cancer during their lifetime. Currently one of the most accepted model/theories is that ductal breast cancer (most common type of breast cancer) follows a linear progression: from normal breast epithelial cells to ductal hyperplasia to atypical ductal hyperplasia (ADH) to ductal carcinoma in situ (DCIS), and finally to invasive ductal carcin...

  9. Effect of Melatonin in Epithelial Mesenchymal Transition Markers and Invasive Properties of Breast Cancer Stem Cells of Canine and Human Cell Lines.

    Directory of Open Access Journals (Sweden)

    Naiane do Nascimento Gonçalves

    Full Text Available Cancer stem cells (CSCs have been associated with metastasis and therapeutic resistance and can be generated via epithelial mesenchymal transition (EMT. Some studies suggest that the hormone melatonin acts in CSCs and may participate in the inhibition of the EMT. The objectives of this study were to evaluate the formation of mammospheres from the canine and human breast cancer cell lines, CMT-U229 and MCF-7, and the effects of melatonin treatment on the modulation of stem cell and EMT molecular markers: OCT4, E-cadherin, N-cadherin and vimentin, as well as on cell viability and invasiveness of the cells from mammospheres. The CMT-U229 and MCF-7 cell lines were subjected to three-dimensional culture in special medium for stem cells. The phenotype of mammospheres was first evaluated by flow cytometry (CD44(+/CD24(low/- marking. Cell viability was measured by MTT colorimetric assay and the expression of the proteins OCT4, E-cadherin, N-cadherin and vimentin was evaluated by immunofluorescence and quantified by optical densitometry. The analysis of cell migration and invasion was performed in Boyden Chamber. Flow cytometry proved the stem cell phenotype with CD44(+/CD24(low/- positive marking for both cell lines. Cell viability of CMT-U229 and MCF-7 cells was reduced after treatment with 1mM melatonin for 24 h (P<0.05. Immunofluorescence staining showed increased E-cadherin expression (P<0.05 and decreased expression of OCT4, N-cadherin and vimentin (P<0.05 in both cell lines after treatment with 1 mM melatonin for 24 hours. Moreover, treatment with melatonin was able to reduce cell migration and invasion in both cell lines when compared to control group (P<0.05. Our results demonstrate that melatonin shows an inhibitory role in the viability and invasiveness of breast cancer mammospheres as well as in modulating the expression of proteins related to EMT in breast CSCs, suggesting its potential anti-metastatic role in canine and human breast cancer

  10. Selection of a MCF-7 Breast Cancer Cell Subpopulation with High Sensitivity to IL-1β: Characterization of and Correlation between Morphological and Molecular Changes Leading to Increased Invasiveness

    OpenAIRE

    Eloy Andres Pérez-Yépez; Jorge-Tonatiuh Ayala-Sumuano; Alicia Maria Reveles-Espinoza; Isaura Meza

    2012-01-01

    Cancer and inflammation are closely related in tumor malignancy prognosis. Breast cancer MCF-7 cells have a poor invasive phenotype, although, under IL-1 β stimulus, acquire invasive features. Cell response heterogeneity has precluded precise evaluation of the malignant transition. MCF-7A3 cells were selected for high sensitivity to IL-1 β stimulus, uniform expression of CXCR4, and stability of IL1-RI. Structural changes, colony formation ability, proliferation rate, chemotaxis, Matrigel inva...

  11. 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 ...

  12. lacZ transduced human breast cancer xenografts as an in vivo model for the study of invasion and metastasis

    DEFF Research Database (Denmark)

    Brünner, N; Thompson, E W; Spang-Thomsen, M;

    1992-01-01

    A number of human cancer cell lines have been described as being invasive and metastatic in immune incompetent animals. However, it is difficult to assess metastatic spread of a subcutaneously injected or inoculated cell line, since an exact detection of all microfoci of human tumour cells in the...

  13. PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer.

    Science.gov (United States)

    Yan, Li-Xu; Liu, Yan-Hui; Xiang, Jian-Wen; Wu, Qi-Nian; Xu, Lei-Bo; Luo, Xin-Lan; Zhu, Xiao-Lan; Liu, Chao; Xu, Fang-Ping; Luo, Dong-Lan; Mei, Ping; Xu, Jie; Zhang, Ke-Ping; Chen, Jie

    2016-02-01

    We have previously shown that dysregulation of miR-21 functioned as an oncomiR in breast cancer. The aim of the present study was to elucidate the mechanisms by which miR-21 regulate breast tumor migration and invasion. We applied pathway analysis on genome microarray data and target-predicting algorithms for miR-21 target screening, and used luciferase reporting assay to confirm the direct target. Thereafter, we investigated the function of the target gene phosphoinositide-3-kinase, regulatory subunit 1 (α) (PIK3R1), and detected PIK3R1 coding protein (p85α) by immunohistochemistry and miR-21 by RT-qPCR on 320 archival paraffin-embedded tissues of breast cancer to evaluate the correlation of their expression with prognosis. First, we found that PIK3R1 suppressed growth, invasiveness, and metastatic properties of breast cancer cells. Next, we identified the PIK3R1 as a direct target of miR-21 and showed that it was negatively regulated by miR-21. Furthermore, we demonstrated that p85α overexpression phenocopied the suppression effects of antimiR-21 on breast cancer cell growth, migration and invasion, indicating its tumor suppressor role in breast cancer. On the contrary, PIK3R1 knockdown abrogated antimiR‑21-induced effect on breast cancer cells. Notably, antimiR-21 induction increased p85α, accompanied by decreased p-AKT level. Besides, antimiR-21/PIK3R1-induced suppression of invasiveness in breast cancer cells was mediated by reversing epithelial-mesenchymal transition (EMT). p85α downregulation was found in 25 (7.8%) of the 320 breast cancer patients, and was associated with inferior 5-year disease-free survival (DFS) and overall survival (OS). Taken together, we provide novel evidence that miR-21 knockdown suppresses cell growth, migration and invasion partly by inhibiting PI3K/AKT activation via direct targeting PIK3R1 and reversing EMT in breast cancer. p85α downregulation defined a specific subgroup of breast cancer with shorter 5-year DFS and OS

  14. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  15. Characterization of a Test for Invasive Breast Cancer Using X-ray Diffraction of Hair - Results of a Clinical Trial

    Directory of Open Access Journals (Sweden)

    Gary L. Corino

    2009-11-01

    Full Text Available Objective: To assess the performance of a test for breast cancer utilizing synchrotron x-ray diffraction analysis of scalp hair from women undergoing diagnostic radiology assessment. Design and Setting: A double-blinded clinical trial of women who attended diagnostic radiology clinics in Australia. Patients: 1796 women referred for diagnostic radiology, with no previous history of cancer. Main Outcome Measures: Sensitivity, specificity and accuracy of the hair test analysis compared to the gold standard of imaging followed by biopsy where indicated. Results: The hair-based assay had an overall accuracy of >77% and a negative predictive value of 99%. For all women, the sensitivity of both mammography and x-ray diffraction alone was 64%, but when used together the sensitivity rose to 86%. The sensitivity of the hair test for women under the age of 70 was 74%. Conclusion: In this large population trial the association between the presence of breast cancer and an altered hair fibre X-ray diffraction pattern previously reported has been confirmed. It appears that mammography and X-ray diffraction of hair detect different populations of breast cancers, and are synergistic when used together.

  16. 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...

  17. 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...

  18. European Breast Cancer Service Screening Outcomes

    DEFF Research Database (Denmark)

    Paci, Eugenio; Broeders, Mireille; Hofvind, Solveig;

    2014-01-01

    A recent comprehensive review has been carried out to quantify the benefits and harms of the European population-based mammographic screening programs. Five literature reviews were conducted on the basis of the observational published studies evaluating breast cancer mortality reduction, breast...... seven to nine breast cancer deaths are avoided, four cases are overdiagnosed, 170 women have at least one recall followed by noninvasive assessment with a negative result, and 30 women have at least one recall followed by invasive procedures yielding a negative result. The chance of a breast cancer...

  19. Overexpression of ubiquitin carboxyl terminal hydrolase-L1 enhances multidrug resistance and invasion/metastasis in breast cancer by activating the MAPK/Erk signaling pathway.

    Science.gov (United States)

    Wang, Wenjuan; Zou, Liping; Zhou, Danmei; Zhou, Zhongwen; Tang, Feng; Xu, Zude; Liu, Xiuping

    2016-09-01

    Multidrug resistant (MDR) cancer cells overexpressing P-glycoprotein (P-gp) exhibit enhanced invasive/metastatic ability as compared with the sensitive cells. We aimed to clarify the mechanism underlying this observation and found that during the development of drug resistance to adriamycin in MCF7 cells, the elevated expression of UCH-L1 coincides with the up-regulation of MDR1, CD147, MMP2, and MMP9 as well as increased cellular migration/invasion. Overexpression of UCH-L1 in MCF7 cells up-regulated MDR1, CD147, MMP2, and MMP9, which conferred MDR and promoted migration/invasion. On the other hand, silencing of UCH-L1 in MCF7/Adr cells led to the opposite effect. Immunohistochemistry in 203 breast cancer samples revealed that UCH-L1 expression is positively correlated with P-gp, CD147, MMP2, and MMP9 expression and standard tumor spread indicators. Kaplan-Meier survival analysis indicated a correlation between UCH-L1 expression and shorter recurrent and survival times. Moreover, UCH-L1-overexpressing clones treated with U0126 (an Erk1/2-specific inhibitor) significantly decreased the expression of MDR1, CD147, MMP2, and MMP9. These data indicate that UCH-L1 may assume a dual role, because it had intrinsic stimulatory effects on tumor migration/invasion and increased MDR. © 2015 Wiley Periodicals, Inc. PMID:26293643

  20. PRL-3 engages the focal adhesion pathway in triple-negative breast cancer cells to alter actin structure and substrate adhesion properties critical for cell migration and invasion.

    Science.gov (United States)

    Gari, Hamid H; DeGala, Gregory D; Ray, Rahul; Lucia, M Scott; Lambert, James R

    2016-10-01

    Triple-negative breast cancers (TNBCs) are among the most aggressive cancers characterized by a high propensity to invade, metastasize and relapse. We previously reported that the TNBC-specific inhibitor, AMPI-109, significantly impairs the ability of TNBC cells to migrate and invade by reducing levels of the metastasis-promoting phosphatase, PRL-3. Here, we examined the mechanisms by which AMPI-109 and loss of PRL-3 impede cell migration and invasion. AMPI-109 treatment or knock down of PRL-3 expression were associated with deactivation of Src and ERK signaling and concomitant downregulation of RhoA and Rac1/2/3 GTPase protein levels. These cellular changes led to rearranged filamentous actin networks necessary for cell migration and invasion. Conversely, overexpression of PRL-3 promoted TNBC cell invasion by upregulating matrix metalloproteinase 10, which resulted in increased TNBC cell adherence to, and degradation of, the major basement membrane component laminin. Our data demonstrate that PRL-3 engages the focal adhesion pathway in TNBC cells as a key mechanism for promoting TNBC cell migration and invasion. Collectively, these data suggest that blocking PRL-3 activity may be an effective method for reducing the metastatic potential of TNBC cells. PMID:27452906

  1. Is there different correlation with prognostic factors between “non-mass” and “mass” type invasive ductal breast cancers?

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Lei, E-mail: jiang_belinder@sina.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Zhou, Yiming, E-mail: zhou_belly@sina.com [Radiology Department, Chaoyang Hospital, Capital University, Baijiazhuang Road 8#, Chaoyang District, Beijing 100020 (China); Wang, Zheng, E-mail: wangzhengmay@163.com [Pathology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Lu, Xu, E-mail: luxu01@sina.cn [Surgery Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Chen, Min, E-mail: chenmin62@yahoo.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Zhou, Cheng, E-mail: Chengzhou2000@yahoo.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China)

    2013-09-15

    Purpose: To investigate the association between non-mass type breast cancer and common clinical–pathological prognostic factors, compared with mass type breast cancer. Materials and methods: After institutional review board approval, retrospective blind review of contrast-enhanced breast MRI was carried out for 88 histologically proven breast invasive ductal carcinoma (IDC) patients, presenting from January 2008 to December 2011. Two radiologists assessed the images of each lesion for the morphologic enhancement type [mass enhancement or non-mass-like enhancement (NMLE)] and the distribution/internal enhancement of NMLE. Two pathologists evaluated the histological grade of IDC, presence or absence of ductal carcinoma in situ (DCIS), lymph node status, presence or absence of vascular invasion, and expression status of estrogen receptor (ER)/progesterone receptor (PR)/HER-2/p53 tumor suppressor gene (p53)/Ki-67. Inter-observer agreement was assessed with kappa test. Chi-square test and Spearman rank correlation were performed to explore the associations of morphologic enhancement type with the age, lesion size and the above pathological prognostic factors Results: Inter-observer agreement was excellent, with kappa > 0.75. Morphologic enhancement type was significantly correlated with age (P = 0.02), with NMLE more commonly seen in women less than 50 y/o. The size of NMLE was larger than that of mass and, with the increase of lesion size, proportion of NMLE among the cases increased (P = 0.001). NMLE was also significantly correlated with low histologic grade of IDC (P = 0.003) and presence of DCIS (P < 0.001). There was no significant correlation between morphologic enhancement type and lymph node status, vascular invasion, ER/PR/HER-2/p53/Ki-67 status. The histological grade was higher in clumped enhancement than non-clumped (P = 0.011). There was no correlation between enhancement distribution and prognostic factors Conclusions: Non-mass type breast cancer may

  2. Epithelial-Mesenchymal Transition and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yanyuan Wu

    2016-01-01

    Full Text Available Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges.

  3. Detection of pAkt protein in imprint cytology of invasive breast cancer: Correlation with HER2/neu, hormone receptors, and other clinicopathological variables

    Directory of Open Access Journals (Sweden)

    Olympia Vasou

    2015-01-01

    Full Text Available Purpose: Akt is a serine/threonine protein kinase and has emerged as a crucial regulator of widely divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Activation of Akt/protein kinase B has been positively associated with human epidermal growth-factor receptor 2 (HER2/neu overexpression in breast carcinoma and a worse outcome among endocrine treated patients. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Methods: Archival tumor tissues from 100 patients with invasive breast carcinoma were analyzed by immunocytochemistry. This study describes the results of immunocytochemical pAkt expression in breast carcinoma imprints, prepared from cut surfaces of freshly removed tumors . Both nuclear and cytoplasmic expressions were evaluated for pAkt. Results: Nuclear and cytoplasmic positive scores of 72% (72/100 and 42% (42/100, respectively, were found. Coexistence of nuclear and cytoplasmic staining was observed in 32 cases (32/100. Nuclear positive staining correlated with HER2/neu overexpression (P = 0.043 and was significantly associated with positive involvement of axillary lymph nodes (P = 0.013. No correlation was found between cytoplasmic pAkt rate and clinicopathological parameters, estrogen receptor, progesterone receptor or HER2/neu expression. Conclusions: pAkt expression can be evaluated in cytological material and may add valuable information to current prognostic models for breast cancer. pAkt overexpression appears to be linked with potentially aggressive tumor phenotype in invasive breast carcinoma.

  4. Immunohistochemical analysis of Metadherin in proliferative and cancerous breast tissue

    OpenAIRE

    Zhang Qinghui; Su Peng; Yang Qifeng

    2010-01-01

    Abstract Background Metadherin (MTDH) has been reported to be associated with cancer progression in various types of human cancers including breast cancer. Whether MTDH contributes to carcinogenesis of breast cancer is still unknown. In the present study, we investigated the expression of MTDH in normal, UDH (usual ductal hyperplasia), ADH (atypical ductal hyperplasia), DCIS (ductal carcinoma in situ) and invasive cancer to explore the possible role of MTDH for breast cancer carcinogenesis. M...

  5. Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity123

    Science.gov (United States)

    Ferrari-Amorotti, Giovanna; Chiodoni, Claudia; Shen, Fei; Cattelani, Sara; Soliera, Angela Rachele; Manzotti, Gloria; Grisendi, Giulia; Dominici, Massimo; Rivasi, Francesco; Colombo, Mario Paolo; Fatatis, Alessandro; Calabretta, Bruno

    2014-01-01

    Most triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic spread of TNBC cell lines. We show here that PCPA treatment induces the expression of E-cadherin and other epithelial markers and markedly suppresses migration and invasion of TNBC cell lines MDA-MB-231 and BT-549. These effects were phenocopied by Slug or LSD1 silencing. In two models of orthotopic breast cancer, PCPA treatment reduced local tumor growth and the number of lung metastases. In mice injected directly in the blood circulation with MDA-MB-231 cells, PCPA treatment or Slug silencing markedly inhibited bone metastases but had no effect on lung infiltration. Thus, blocking Slug activity may suppress the metastatic spread of TNBC and, perhaps, specifically inhibit homing/colonization to the bone. PMID:25499218

  6. 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.

  7. A human breast cell model of pre-invasive to invasive transition

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  8. Interleukin-8 in breast cancer progression.

    Science.gov (United States)

    Todorović-Raković, Nataša; Milovanović, Jelena

    2013-10-01

    Interleukin-8 (IL-8) is a chemokine that has an autocrine and/or paracrine tumor-promoting role and significant potential as a prognostic and/or predictive cancer biomarker. In breast cancer, which is mostly determined by expression of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), IL-8 could play a specific role. IL-8 is highly expressed in ER- breast cancers, but it increases invasiveness and metastatic potential of both ER- and ER+ breast cancer cells. It is also highly expressed in HER2+ breast cancers. Because of the complex crosstalk between these receptors and IL-8, its role is mainly determined by delicate balance in their signaling pathways. Therefore, the main point of this review was to analyze the possible influence of IL-8 in breast cancer progression related to its interaction with ER and HER2 and the consequent therapeutic implications of these relations.

  9. 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...

  10. Primary synchronous bilateral breast cancer

    Directory of Open Access Journals (Sweden)

    R Krishnappa

    2014-01-01

    Full Text Available Background: Primary synchronous bilateral breast cancer (PSBBC is a rare clinical entity. The reported incidence ranges between 0.3% and 12%. There are several controversial issues regarding PSBBC pertaining to the diagnostic criteria, nomenclature, and management policies. Materials and Methods: Fourteen cases of PSBBC treated between 2001 to 2010 at our institute were retrospectively analysed in regards to demographic data, management and follow up. Results: PSBBC constituted 0.19% of total breast cancer patients at our institute. Age ranged from 28 to 78 years. PSBBC were detected by clinical examination in eight cases and by mammography in six cases. Twelve patients underwent bilateral modified radical mastectomy, one had unilateral mastectomy on one side and breast conservation on the other side and one patient has bilateral breast conservation. Majority of patients belonged to stage 2 and stage 3. All patients were found to have invasive ductal carcinoma. Five cases were ER/PR positive and 8 patients were triple hormone receptor negative. Eight patients received unilateral and six received bilateral adjuvant radiotherapy. Nine patients received adjuvant chemotherapy. 5 patients received adjuvant hormonal therapy. Median follow up of patients was 15.4 months. Conclusion: PSBBC is a rare event warranting awareness and screening of the contralateral breast in patients with unilateral breast cancer. These patients require individualized treatment planning based on the tumor factors of the index lesion. Further multi institutional prospective studies are needed for adequate understanding of management of PSBBC.

  11. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard;

    2010-01-01

    and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF...... tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria......ABSTRACT: Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development...

  12. 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

  13. 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 ...

  14. Interleukin-8 upregulates integrin β3 expression and promotes estrogen receptor-negative breast cancer cell invasion by activating the PI3K/Akt/NF-κB pathway.

    Science.gov (United States)

    Shao, Nan; Lu, Zhenhai; Zhang, Yunjian; Wang, Mian; Li, Wen; Hu, Ziye; Wang, Shenming; Lin, Ying

    2015-08-10

    Interleukin-8 (IL-8) possesses tumorigenic and proangiogenic properties and is overexpressed in many human cancers. The integrin family regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumors. However, the mechanisms of action of IL-8 and integrin in estrogen receptor-negative breast cancer are largely unknown. In this study, IL-8 and integrin β3 expression in human breast cancer cells and tissues was examined by real-time PCR, Western blot and immunochemistry analysis. Integrin β3 expression, invasive ability and the activation of PI3K/Akt and NF-κB pathways in IL-8 knockdown breast cancer cells were evaluated. In addition, reporter assay and ChIP were performed to assess integrin β3 promoter activity in IL-8 knockdown cells. We observed a positive correlation between integrin β3 and IL-8 expression, which was inversely correlated with ER status in breast cancer cell lines and tissues. IL-8 siRNA decreased the invasion and integrin β3 expression in human breast cancer cells. Moreover, IL-8 siRNA attenuated the phosphorylation of PI3K and Akt and inhibited NF-κB activity and binding on integrin β3 promoter. IL-8 siRNA diminished NF-κB nuclear translocation via blocking IκB phosphorylation in the cytoplasm. In conclusion, IL-8 activates the PI3K/Akt pathway, which in turn activates NF-κB, resulting in the upregulation of integrin β3 expression and increased invasion of estrogen receptor-negative breast cancer cells. IL-8/PI3K/Akt/NF-κB/integrin β3 axis may be exploited for therapeutic intervention to breast cancer metastasis.

  15. 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.

  16. 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 ...

  17. Prevalence of molecular subtypes and prognosis of invasive breast cancer in north-east of Morocco: retrospective study

    Directory of Open Access Journals (Sweden)

    Bennis Sanae

    2012-08-01

    Full Text Available Abstract Background Breast carcinoma is known as a heterogeneous disease because gene expression analyses identify several subtypes and the molecular profiles are prognostic and predictive for patients. Our aim, in this study, is to estimate the prevalence of breast cancer subtypes and to determine the relationship between clinico-pathological characteristics, overall survival (OS and disease free survival (DFS for patients coming from north-east of Morocco. Methods We reviewed 366 cases of breast cancer diagnosed between January 2007 to June 2010 at the Department of pathology. Age, size tumor, metastatic profile, node involvement profile, OS and DFS were analyzed on 181 patients. These last parameters were estimated by Kaplan-Meier analysis and log-rank test to estimate outcome differences among subgroups. Results The average age was 45 years, our patients were diagnosed late (57% stage III, 17.5% stage IV with a high average tumor size. Luminal A subtype was more prevalent (53.6% associated with favorable clinic-pathological characteristics, followed by luminal B (16.4%, Her2-overexpressing (12.6%, basal-like (12.6% and unclassified subtype (4.9%. Survival analysis showed a significant difference between subtypes. The triple negative tumors were associated with poor prognosis (49% OS, 39% DFS, whereas the luminal A were associated with a better prognosis (88% OS, 59% DFS. The luminal B and the Her2-overexpressing subtypes were associated with an intermediate prognosis (77% and 75% OS, and 41% and 38% DFS respectively. Conclusion This study showed that molecular classification by immunohistochemistry was necessary for therapeutic decision and prognosis of breast carcinoma. The luminal A subtype was associated with favorable biological characteristics and a better prognosis than triple negative tumors that were associated with a poor prognosis and unfavorable clinic-pathological characteristics.

  18. Isoalantolactone inhibits the migration and invasion of human breast cancer MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway.

    Science.gov (United States)

    Wang, Jing; Cui, Li; Feng, Liang; Zhang, Zhenhai; Song, Jie; Liu, Dan; Jia, Xiaobin

    2016-09-01

    Isoalantolactone is a bioactive sesquiterpene lactone isolated from the flowering plant Inula helenium L. This study was conducted to assess the anti-migratory and anti-invasive activities of isoalantolactone in MDA-MB-231 cells, and to explore the underlying mechanisms. Wound-healing and Transwell chambers assays demonstrated that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells. The activity and expression of MMP-2 and MMP-9 were downregulated by isoalantolactone in a dose-dependent manner. Additionally, isoalantolactone markedly decreased the p-p38 MAPK level, whereas no significant change in p-ERK1/2 and p-JNK1/2 was noted. The downregulation of MMP-2 and MMP-9 protein expression and suppression of in vitro invasion might be associated with the blockade of p38 MAPK activation. Furthermore, isoalantolactone blocked the translocation of NF-κB p65 from the cytoplasm into the nucleus. These results revealed that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway, and isoalantolactone might be an alternative treatment for breast cancer. PMID:27461575

  19. RAB2A controls MT1-MMP endocytic and E-cadherin polarized Golgi trafficking to promote invasive breast cancer programs.

    Science.gov (United States)

    Kajiho, Hiroaki; Kajiho, Yuko; Frittoli, Emanuela; Confalonieri, Stefano; Bertalot, Giovanni; Viale, Giuseppe; Di Fiore, Pier Paolo; Oldani, Amanda; Garre, Massimiliano; Beznoussenko, Galina V; Palamidessi, Andrea; Vecchi, Manuela; Chavrier, Philippe; Perez, Frank; Scita, Giorgio

    2016-07-01

    The mechanisms of tumor cell dissemination and the contribution of membrane trafficking in this process are poorly understood. Through a functional siRNA screening of human RAB GTPases, we found that RAB2A, a protein essential for ER-to-Golgi transport, is critical in promoting proteolytic activity and 3D invasiveness of breast cancer (BC) cell lines. Remarkably, RAB2A is amplified and elevated in human BC and is a powerful and independent predictor of disease recurrence in BC patients. Mechanistically, RAB2A acts at two independent trafficking steps. Firstly, by interacting with VPS39, a key component of the late endosomal HOPS complex, it controls post-endocytic trafficking of membrane-bound MT1-MMP, an essential metalloprotease for matrix remodeling and invasion. Secondly, it further regulates Golgi transport of E-cadherin, ultimately controlling junctional stability, cell compaction, and tumor invasiveness. Thus, RAB2A is a novel trafficking determinant essential for regulation of a mesenchymal invasive program of BC dissemination. PMID:27255086

  20. Epidermal growth factor (EGF and interleukin (IL-1β synergistically promote ERK1/2-mediated invasive breast ductal cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Ma Liqiang

    2012-10-01

    Full Text Available Abstract Background Patients with invasive breast ductal carcinoma (IBDC with metastasis have a very poor prognosis. Little is known about the synergistic action of growth and inflammatory factors in IBDC metastases. Methods The expression of activated extracellular signal-regulated kinase1/2 (phosphorylated or p-ERK1/2 was analyzed by immunohistochemistry in IBDC tissue samples from 80 cases. BT474 IBDC cell migration and invasion were quantified using the Transwell assay. Matrix metalloproteinase (MMP-9 expression and activity were analyzed by RT-PCR, Western blotting and zymography. Activator protein (AP-1 activity was measured with a luciferase reporter gene assay. The Wilcoxon signed-rank test, Chi-square test, the partition of Chi-square test, independent t-test, and Spearman’s method were used for the statistical analysis. Results Phosphorylated ERK1/2 was detected in 58/80 (72.5% IBDC tissues, and was associated with higher TNM stage and lymph node metastasis, but not patient age or tumor size. Individually, epidermal growth factor (EGF, and interleukin (IL-1β activated ERK1/2, increased cell migration and invasion, MMP-9 expression and activity, AP-1 activation in vitro and the expression of p-ERK1/2 was positively correlated with EGF expression levels, as well as IL-1β, MMP-9 and c-fos in IBDC tissue samples. Co-stimulation with EGF and IL-1β synergistically increased ERK1/2 and AP-1 activation, cell migration and invasion, and MMP-9 expression and activity. Inhibition of ERK1/2 using U0126 or siRNA abolished EGF and/or IL-1β-induced cell migration and invasion in a dose-dependent manner. Conclusion Activated ERK1/2 was associated with higher TNM stage and lymph node metastasis in IBDC. Both in vitro and in vivo studies indicated that ERK-1/2 activation may increase the metastatic ability of IBDC cells. Growth and inflammatory factors synergistically induced IBDC cell migration and invasion via ERK1/2 signaling, AP-1 activation

  1. 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 ...

  2. Development and evaluation of a prediction model for underestimated invasive breast cancer in women with ductal carcinoma in situ at stereotactic large core needle biopsy.

    Directory of Open Access Journals (Sweden)

    Suzanne C E Diepstraten

    Full Text Available BACKGROUND: We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery. METHODS: From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic large core needle biopsy, drawn from the prospective COBRA (Core Biopsy after RAdiological localization and COBRA2000 cohort studies, were used to fit the multivariable model and assess its overall performance, discrimination, and calibration. RESULTS: 348 women with large core needle biopsy-proven ductal carcinoma in situ were available for analysis. In 100 (28.7% patients invasive carcinoma was found at subsequent surgery. Nine predictors were included in the model. In the multivariable analysis, the predictors with the strongest association were lesion size (OR 1.12 per cm, 95% CI 0.98-1.28, number of cores retrieved at biopsy (OR per core 0.87, 95% CI 0.75-1.01, presence of lobular cancerization (OR 5.29, 95% CI 1.25-26.77, and microinvasion (OR 3.75, 95% CI 1.42-9.87. The overall performance of the multivariable model was poor with an explained variation of 9% (Nagelkerke's R(2, mediocre discrimination with area under the receiver operating characteristic curve of 0.66 (95% confidence interval 0.58-0.73, and fairly good calibration. CONCLUSION: The evaluation of our multivariable prediction model in a large, clinically representative study population proves that routine clinical and pathological variables are not suitable to select patients with large core needle biopsy-proven ductal carcinoma in situ for sentinel node biopsy during primary surgery.

  3. Male breast cancer.

    Science.gov (United States)

    Ottini, Laura; Palli, Domenico; Rizzo, Sergio; Federico, Mario; Bazan, Viviana; Russo, Antonio

    2010-02-01

    Male breast cancer (MaleBC) is a rare disease, accounting for development; low-penetrance gene mutations (i.e. CHEK-2) are more common but involve a lower risk increase. About 90% of all male breast tumors have proved to be invasive ductal carcinomas, expressing high levels of hormone receptors with evident therapeutic returns. The most common clinical sign of BC onset in men is a painless palpable retroareolar lump, which should be evaluated by means of mammography, ultrasonography and core biopsy or fine needle aspiration (FNA). To date, there are no published data from prospective randomized trials supporting a specific therapeutic approach in MaleBC. Tumor size together with the number of axillary nodes involved are the main prognostic factors and should guide the treatment choice. Locoregional approaches include surgery and radiotherapy (RT), depending upon the initial clinical presentation. When systemic treatment (adjuvant, neoadjuvant and metastatic) is delivered, the choice between hormonal and or chemotherapy (CT) should depend upon the clinical and biological features, according to the FBC management guidelines. However great caution is required because of high rates of age-related comorbidities. PMID:19427229

  4. MODERN VIEWS ON BILATERAL BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Ye. A. Fesik

    2014-01-01

    Full Text Available Presented modern literature data on the features of the pathogenesis, course, clinical and morphological expression and tumor characteristics, parameters and nodal metastasis of hematogenous bilateral breast cancer. Highlight the results of domestic and foreign studies in recent years to determine the prognostic factors and recurrence of synchronous and metachronous bilateral breast cancer. It was revealed that the frequency of bilateral breast tumor lesions varies widely, ranging from 0.1 to 20%, with metachronous tumors recorded significantly higher (69.6% than the synchronous (22.7%. The probability of occurrence of metachronous breast cancer is higher in women with a family history, as well as if they have a gene mutation BRCA-1. Found that the most common histological type of breast tumor with bilateral lesions is invasive ductal. However, the incidence of invasive lobular cancer and non-invasive lobular cancer is slightly higher among synchronous bilateral cancer compared with unilateral disease. Studies have shown that in a double-sided synchronous breast cancer tumor, as a rule, has a lower degree of differentiation, and the higher the expression level of estrogen receptors and progesterone receptors. Relevance of the issue because the identification of patterns in the study of lymphatic and hematogenous features bilateral metastasis of mammary tumors provides a basis for speculation about the differences in the progression of neoplastic disease in these groups and is a cause for further detailed research in this area to identify and evaluate the prognosis and also the choice of tactics of such patients.

  5. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Thomas W Owens

    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.

  6. Alcohol consumption before and after breast cancer diagnosis: associations with survival from breast cancer, cardiovascular disease, and other causes

    NARCIS (Netherlands)

    Newcomb, P.A.; Kampman, E.; Trentham-Dietz, A.; Egan, K.M.; Titus, L.J.; Baron, J.A.; Hampton, J.M.; Passarelli, M.N.; Willett, W.C.

    2013-01-01

    Purpose Alcohol intake is associated with increased risk of breast cancer. In contrast, the relation between alcohol consumption and breast cancer survival is less clear. Patients and Methods We assessed pre- and postdiagnostic alcohol intake in a cohort of 22,890 women with incident invasive breast

  7. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    NARCIS (Netherlands)

    E.J. Sawyer (Elinor); R. Roylance (Rebecca); C. Petridis (Christos); R.H. Brook; S. Nowinski (Salpie); E. Papouli (Efterpi); O. Fletcher (Olivia); S. Pinder (Sarah); A. Hanby (Andrew); K. Kohut (Kelly); P. Gorman (Patricia); M. Caneppele (Michele); J. Peto (Julian); I. dos Santos Silva (Isabel); N. Johnson (Nichola); R. Swann (Ruth); M. Dwek (Miriam); K.-A. Perkins (Katherine-Anne); C. Gillett (Cheryl); R. Houlston (Richard); G. Ross (Gillian); P. de Ieso (Paolo); M.C. Southey (Melissa); J.L. Hopper (John); E. Provenzano (Elena); C. Apicella (Carmel); J. Wesseling (Jelle); S. Cornelissen (Sten); J.N. Keeman; P.A. Fasching (Peter); S.M. Jud (Sebastian); A.B. Ekici (Arif); M.W. Beckmann (Matthias); M. Kerin (Michael); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); B. Burwinkel (Barbara); P. Guénel (Pascal); T. Truong (Thérèse); P. Laurent-Puig (Pierre); P. Kerbrat (Pierre); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); R.L. Milne (Roger); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); J. Benítez (Javier); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); P. Lichtner (Peter); R.K. Schmutzler (Rita); M. Lochmann (Magdalena); H. Brauch (Hiltrud); H.-P. Fischer; Y-D. Ko (Yon-Dschun); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); G. Chenevix-Trench (Georgia); D. Lambrechts (Diether); C. Weltens (Caroline); E. van Limbergen (Erik); S. Hatse (Sigrid); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P. Radice (Paolo); P. Peterlongo (Paolo); B. Bonnani (Bernardo); S. Volorio (Sara); G.G. Giles (Graham); G. Severi (Gianluca); L. Baglietto (Laura); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); V. Kristensen (Vessela); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); P. Devillee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); M. Kriege (Mieke); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); M.E. Sherman (Mark); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); C.H.M. van Deurzen (Carolien); J. Li (Jingmei); K. Czene (Kamila); M.K. Humphreys (Manjeet); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); M. Shah (Mitul); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); F.J. Couch (Fergus); B. Hallberg (Boubou); A. González-Neira (Anna); G. Pita (G.); M.R. Alonso (M Rosario); Y. Tessier (Yann); D. Vincent (Daniel); F. Bacot (Francois); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); A.M. Dunning (Alison); P. Hall (Per); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); M.K. Schmidt (Marjanka); I.P. Tomlinson (Ian); M. García-Closas (Montserrat)

    2014-01-01

    textabstractInvasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to b

  8. FAK activation is required for IGF1R-mediated regulation of EMT, migration, and invasion in mesenchymal triple negative breast cancer cells.

    Science.gov (United States)

    Taliaferro-Smith, LaTonia; Oberlick, Elaine; Liu, Tongrui; McGlothen, Tanisha; Alcaide, Tiffanie; Tobin, Rachel; Donnelly, Siobhan; Commander, Rachel; Kline, Erik; Nagaraju, Ganji Purnachandra; Havel, Lauren; Marcus, Adam; Nahta, Rita; O'Regan, Ruth

    2015-03-10

    Triple negative breast cancer (TNBC) is a highly metastatic disease that currently lacks effective prevention and treatment strategies. The insulin-like growth factor 1 receptor (IGF1R) and focal adhesion kinase (FAK) signaling pathways function in numerous developmental processes, and alterations in both are linked with a number of common pathological diseases. Overexpression of IGF1R and FAK are closely associated with metastatic breast tumors. The present study investigated the interrelationship between IGF1R and FAK signaling in regulating the malignant properties of TNBC cells. Using small hairpin RNA (shRNA)-mediated IGF1R silencing methods, we showed that IGF1R is essential for sustaining mesenchymal morphologies of TNBC cells and modulates the expression of EMT-related markers. We further showed that IGF1R overexpression promotes migratory and invasive behaviors of TNBC cell lines. Most importantly, IGF1R-driven migration and invasion is predominantly mediated by FAK activation and can be suppressed using pharmacological inhibitors of FAK. Our findings in TNBC cells demonstrate a novel role of the IGF1R/FAK signaling pathway in regulating critical processes involved in the metastatic cascade. These results may improve the current understanding of the basic molecular mechanisms of TNBC metastasis and provide a strong rationale for co-targeting of IGF1R and FAK as therapy for mesenchymal TNBCs. PMID:25749031

  9. Genetic determinants of breast cancer risk

    OpenAIRE

    Li, Jingmei

    2011-01-01

    The main purpose of this thesis was to identify genetic risk factors using both hypothesis-based and hypothesis-free approaches. In an attempt to identify common disease susceptibility alleles for breast cancer, we started off with a hypothesis-free approach, and performed a combined analysis of three genome-wide association studies (GWAS), involving 2,702 women of European ancestry with invasive breast cancer and 5,726 controls. As GWAS has been said to underperform for stu...

  10. Breast Cancer Chemoprevention: Old and New Approaches

    OpenAIRE

    Massimiliano Cazzaniga; Bernardo Bonanni

    2012-01-01

    In 1976, Sporn has defined chemoprevention as “the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred.” Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings i...

  11. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E;

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...... stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations...

  12. Invasive ductal carcinoma of the breast in a 14-year-old girl

    International Nuclear Information System (INIS)

    Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer. (orig.)

  13. Invasive ductal carcinoma of the breast in a 14-year-old girl

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joo Yeon; Kim, Yun Ju; Kim, Sung Hun; Kang, Bong Joo [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Department of Radiology, Seoul (Korea, Republic of); Song, Byung Joo [The Catholic University of Korea, Department of General Surgery, Seoul St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

    2014-11-15

    Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer. (orig.)

  14. Neighborhood socioeconomic deprivation, tumor subtypes, and causes of death after non-metastatic invasive breast cancer diagnosis: a multilevel competing-risk analysis.

    Science.gov (United States)

    Lian, Min; Pérez, Maria; Liu, Ying; Schootman, Mario; Frisse, Ann; Foldes, Ellen; Jeffe, Donna B

    2014-10-01

    The purpose of this study is to examine the associations of neighborhood socioeconomic deprivation and triple-negative breast cancer (TNBC) subtype with causes of death [breast cancer (BC)-specific and non-BC-specific] among non-metastatic invasive BC patients. We identified 3,312 patients younger than 75 years (mean age 53.5 years; 621 [18.8 %] TNBC) with first primary BC treated at an academic medical center from 1999 to 2010. We constructed a census-tract-level socioeconomic deprivation index using the 2000 U.S. Census data and performed a multilevel competing-risk analysis to estimate the hazard ratios (HR) and 95 % confidence intervals (CI) of BC-specific and non-BC-specific mortality associated with neighborhood socioeconomic deprivation and TNBC subtype. The adjusted models controlled for patient sociodemographics, health behaviors, tumor characteristics, comorbidity, and cancer treatment. With a median 62-month follow-up, 349 (10.5 %) patients died; 233 died from BC. In the multivariate models, neighborhood socioeconomic deprivation was independently associated with non-BC-specific mortality (the most- vs. the least-deprived quartile: HR = 2.98, 95 % CI = 1.33-6.66); in contrast, its association with BC-specific mortality was explained by the aforementioned patient-level covariates, particularly sociodemographic factors (HR = 1.15, 95 % CI = 0.71-1.87). TNBC subtype was independently associated with non-BC-specific mortality (HR = 2.15; 95 % CI = 1.20-3.84), while the association between TNBC and BC-specific mortality approached significance (HR = 1.42; 95 % CI = 0.99-2.03, P = 0.057). Non-metastatic invasive BC patients who lived in more socioeconomically deprived neighborhoods were more likely to die as a result of causes other than BC compared with those living in the least socioeconomically deprived neighborhoods. TNBC was associated with non-BC-specific mortality but not BC-specific mortality.

  15. Epidemiology of basal-like breast cancer

    OpenAIRE

    Millikan, Robert C.; Newman, Beth; Tse, Chiu-Kit; Moorman, Patricia G.; Conway, Kathleen; Smith, Lisa. V.; Labbok, Miriam H; Geradts, Joseph; Bensen, Jeannette T.; Jackson, Susan; Nyante, Sarah; Livasy, Chad; Carey, Lisa; Earp, H. Shelton; Perou, Charles M

    2007-01-01

    Risk factors for the newly identified “intrinsic” breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal growth factor receptor 2-positive/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based, case–control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive and in situ breast cancer, and case subtypes were compared to 2,022 controls. Luminal A, the most common s...

  16. NUCKS overexpression in breast cancer

    Directory of Open Access Journals (Sweden)

    Kittas Christos

    2009-08-01

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

  17. Is the presence of mammographic comedo calcification really a prognostic factor for small screen-detected invasive breast cancers?

    International Nuclear Information System (INIS)

    AIM: It has been suggested that the use of traditional prognostic factors such as histological grade and lymph node stage are not reliable predictors of outcome for small (2 = 9.68,P = 0.008). No significant association was demonstrated between the presence of comedo calcification and survival. Multivariate analysis confirmed lymph node stage as the only independent prognostic factor for these small screen-detected breast cancers (χ2 = 7.18,P = 0.007). There were significant associations between the presence of comedo calcification on the screening mammogram and high histological grade and small tumour size. CONCLUSION: Although the overall outcome for small screen-detected breast cancers (<15 mm diameter) is excellent, the presence of lymph node metastases is associated with a significant reduction in long-term survival. The presence of mammographic comedo calcification is not an independent prognostic factor, but is closely related to histological grade. James, J. J. et al. (2003). Clinical Radiology, 58, 54-62

  18. 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

  19. ELK3 Expression Correlates With Cell Migration, Invasion, and Membrane Type 1-Matrix Metalloproteinase Expression in MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Heo, Sun-Hee; Lee, Je-Yong; Yang, Kyung-Min; Park, Kyung-Soon

    2015-01-01

    ELK3 is a member of the Ets family of transcription factors. Its expression is associated with angiogenesis, vasculogenesis, and chondrogenesis. ELK3 inhibits endothelial migration and tube formation through the regulation of MT1-MMP transcription. This study assessed the function of ELK3 in breast cancer (BC) cells by comparing its expression between basal and luminal cells in silico and in vitro. In silico analysis showed that ELK3 expression was higher in the more aggressive basal BC cells than in luminal BC cells. Similarly, in vitro analysis showed that ELK3 mRNA and protein expression was higher in basal BC cells than in normal cells and luminal BC cells. To investigate whether ELK3 regulates basal cell migration or invasion, knockdown was achieved by siRNA in the basal BC cell line MDA-MB-231. Inhibition of ELK3 expression decreased cell migration and invasion and downregulated MT1-MMP, the expression of which is positively correlated with tumor cell invasion. In silico analysis revealed that ELK3 expression was associated with that of MT1-MMP in several BC cell lines (0.98 Pearson correlation coefficient). Though MT1-MMP expression was upregulated upon ELK3 nuclear translocation, ELK3 did not directly bind to the 1.3-kb promoter region of the MT1-MMP gene. These results suggest that ELK3 plays a positive role in the metastasis of BC cells by indirectly regulating MT1-MMP expression. PMID:26637400

  20. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment

    OpenAIRE

    Hsu, Ya-Ling; Hsieh, Chia-Jung; Tsai, Eing-Mei; HUNG, JEN-YU; CHANG, WEI-AN; Hou, Ming-Feng; Kuo, Po-Lin

    2015-01-01

    The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didym...

  1. Urinary estrogen metabolites and breast cancer

    DEFF Research Database (Denmark)

    Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A;

    2013-01-01

    Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1......), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvs...

  2. 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.)

  3. Genomic tumor evolution of breast cancer.

    Science.gov (United States)

    Sato, Fumiaki; Saji, Shigehira; Toi, Masakazu

    2016-01-01

    Owing to recent technical development of comprehensive genome-wide analysis such as next generation sequencing, deep biological insights of breast cancer have been revealed. Information of genomic mutations and rearrangements in patients' tumors is indispensable to understand the mechanism in carcinogenesis, progression, metastasis, and resistance to systemic treatment of breast cancer. To date, comprehensive genomic analyses illustrate not only base substitution patterns and lists of driver mutations and key rearrangements, but also a manner of tumor evolution. Breast cancer genome is dynamically changing and evolving during cancer development course from non-invasive disease via invasive primary tumor to metastatic tumor, and during treatment exposure. The accumulation pattern of base substitution and genomic rearrangement looks gradual and punctuated, respectively, in analogy with contrasting theories for evolution manner of species, Darwin's phyletic gradualism, and Eldredge and Gould's "punctuated equilibrium". Liquid biopsy is a non-invasive method to detect the genomic evolution of breast cancer. Genomic mutation patterns in circulating tumor cells and circulating cell-free tumor DNA represent those of tumors existing in patient body. Liquid biopsy methods are now under development for future application to clinical practice of cancer treatment. In this article, latest knowledge regarding breast cancer genome, especially in terms of 'tumor evolution', is summarized. PMID:25998191

  4. Alcohol and breast cancer tumor subtypes in a Spanish Cohort

    OpenAIRE

    Gago-Dominguez, Manuela; Castelao, J.Esteban; Gude, Francisco; Fernandez, Maite Peña; Miguel E. Aguado-Barrera; Ponte, Sara Miranda; Carmen M Redondo; Castelo, Manuel Enguix; Dominguez, Alejandro Novo; Garzón, Víctor Muñoz; Carracedo, Angel; Martínez, María Elena

    2016-01-01

    Although alcohol intake is an established risk factor for overall breast cancer, few studies have looked at the relationship between alcohol use and breast cancer risk by the four major subtypes of breast cancer and very few data exist in the alcohol-breast cancer relationship in Spanish women. A population-based case-control study was conducted in Galicia, Spain. A total of 1766 women diagnosed with invasive breast cancer between 1997 and 2014 and 833 controls participated in the study. Data...

  5. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    OpenAIRE

    Bruna Karina Banin Hirata; Julie Massayo Maeda Oda; Roberta Losi Guembarovski; Carolina Batista Ariza; Carlos Eduardo Coral de Oliveira; Maria Angelica Ehara Watanabe

    2014-01-01

    Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical m...

  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. 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 Imagery Hypnosis Massage Therapy Mindfulness-Based Stress Reduction Yoga and Breast Cancer Getting ...

  8. 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...

  9. The breast cancer conundrum

    OpenAIRE

    2013-01-01

    For decades, rates of breast cancer have been going up faster in rich countries than in poor ones. Scientists are beginning to understand more about its causes but unanswered questions remain. Patrick Adams reports.

  10. Human mammary fibroblasts stimulate invasion of breast cancer cells in a three-dimensional culture and increase stroma development in mouse xenografts

    International Nuclear Information System (INIS)

    Tumour phenotype is regulated in a complex fashion as a result of interactions between malignant cells and the tumour stroma. Fibroblasts are the most abundant and perhaps most active part of the tumour stroma. A better understanding of the changes that occur in fibroblasts in response to the presence of malignant cells may lead to the development of new strategies for cancer treatment. We explored the effects of fibroblasts on the growth and invasion of mammary carcinoma tumour cells in vitro and in vivo. In order to analyse secreted factors that affect invasive abilities of breast cancer cells we co-cultured human mammary fibroblasts (HMF3s) and cancer cells (MCF7S1) in three-dimensional (3D) growth conditions devoid of heterogeneous cell-cell contact. To study the possible influence of fibroblasts on MCF7S1 cancer cell growth in vivo we co-injected HMF3s and MCF7S1 cells in Balb/c nu/nu mice. In 3D co-culture both HMF3s and MCF7S1 cells demonstrated enhanced invasion into a Matrigel matrix. This was correlated with enhanced expression of the metastasis promoting S100A4 protein in fibroblasts, stimulation of the matrix metalloproteinase (MMP)-2 activity, and enhanced secretion of a range of different cytokines. Orthotopic injection of oestrogen-dependent MCF7S1 cancer cells together with fibroblasts showed stimulation of tumour growth in mice without an external oestrogen supply. The resulting tumours were characterized by increased development of extracellular matrix, as well as an increase of murine S100A4 concentration and activity of MMP-2 in the tumour interstitial fluid. Stimulation of the invasive phenotype of tumour cells in 3D co-cultures with fibroblasts could be correlated with increased production of S100A4 and MMP-2. We propose that enhanced development of mouse host-derived tumour stroma in a MCF7S1 co-injection xenograft model leads to oestrogen independency and is triggered by the initial presence of human fibroblasts

  11. Human mammary fibroblasts stimulate invasion of breast cancer cells in a three-dimensional culture and increase stroma development in mouse xenografts

    Directory of Open Access Journals (Sweden)

    Olsen Charlotta J

    2010-08-01

    Full Text Available Abstract Introduction Tumour phenotype is regulated in a complex fashion as a result of interactions between malignant cells and the tumour stroma. Fibroblasts are the most abundant and perhaps most active part of the tumour stroma. A better understanding of the changes that occur in fibroblasts in response to the presence of malignant cells may lead to the development of new strategies for cancer treatment. We explored the effects of fibroblasts on the growth and invasion of mammary carcinoma tumour cells in vitro and in vivo. Methods In order to analyse secreted factors that affect invasive abilities of breast cancer cells we co-cultured human mammary fibroblasts (HMF3s and cancer cells (MCF7S1 in three-dimensional (3D growth conditions devoid of heterogeneous cell-cell contact. To study the possible influence of fibroblasts on MCF7S1 cancer cell growth in vivo we co-injected HMF3s and MCF7S1 cells in Balb/c nu/nu mice. Results In 3D co-culture both HMF3s and MCF7S1 cells demonstrated enhanced invasion into a Matrigel matrix. This was correlated with enhanced expression of the metastasis promoting S100A4 protein in fibroblasts, stimulation of the matrix metalloproteinase (MMP-2 activity, and enhanced secretion of a range of different cytokines. Orthotopic injection of oestrogen-dependent MCF7S1 cancer cells together with fibroblasts showed stimulation of tumour growth in mice without an external oestrogen supply. The resulting tumours were characterized by increased development of extracellular matrix, as well as an increase of murine S100A4 concentration and activity of MMP-2 in the tumour interstitial fluid. Conclusion Stimulation of the invasive phenotype of tumour cells in 3D co-cultures with fibroblasts could be correlated with increased production of S100A4 and MMP-2. We propose that enhanced development of mouse host-derived tumour stroma in a MCF7S1 co-injection xenograft model leads to oestrogen independency and is triggered by the

  12. Role of KCNMA1 in breast cancer.

    Directory of Open Access Journals (Sweden)

    Martin Oeggerli

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

  13. 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.

  14. Lifetime grain consumption and breast cancer risk.

    Science.gov (United States)

    Farvid, Maryam S; Cho, Eunyoung; Eliassen, A Heather; Chen, Wendy Y; Willett, Walter C

    2016-09-01

    We evaluated individual grain-containing foods and whole and refined grain intake during adolescence, early adulthood, and premenopausal years in relation to breast cancer risk in the Nurses' Health Study II. Grain-containing food intakes were reported on a baseline dietary questionnaire (1991) and every 4 years thereafter. Among 90,516 premenopausal women aged 27-44 years, we prospectively identified 3235 invasive breast cancer cases during follow-up to 2013. 44,263 women reported their diet during high school, and from 1998 to 2013, 1347 breast cancer cases were identified among these women. Cox proportional hazards regression was used to estimate relative risks (RR) and 95 % confidence intervals (95 % CI) of breast cancer for individual, whole and refined grain foods. After adjusting for known breast cancer risk factors, adult intake of whole grain foods was associated with lower premenopausal breast cancer risk (highest vs. lowest quintile: RR 0.82; 95 % CI 0.70-0.97; P trend = 0.03), but not postmenopausal breast cancer. This association was no longer significant after further adjustment for fiber intake. The average of adolescent and early adulthood whole grain food intake was suggestively associated with lower premenopausal breast cancer risk (highest vs lowest quintile: RR 0.74; 95 % CI 0.56-0.99; P trend = 0.09). Total refined grain food intake was not associated with risk of breast cancer. Most individual grain-containing foods were not associated with breast cancer risk. The exceptions were adult brown rice which was associated with lower risk of overall and premenopausal breast cancer (for each 2 servings/week: RR 0.94; 95 % CI 0.89-0.99 and RR 0.91; 95 % CI 0.85-0.99, respectively) and adult white bread intake which was associated with increased overall breast cancer risk (for each 2 servings/week: RR 1.02; 95 % CI 1.01-1.04), as well as breast cancer before and after menopause. Further, pasta intake was inversely associated with

  15. Regulation of In Situ to Invasive Breast CarcinomaTransition

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Min; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen,Haiyan; Carrasco, Daniel; Richardson, Andrea; Bissell, Mina; Violette,Shelia; Gelman, Rebecca S.; Schnitt, Stuart; Polyak, Kornelia

    2007-03-13

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  16. Regulation of in situ to invasive breast carcinoma transition

    Energy Technology Data Exchange (ETDEWEB)

    Polyak, Kornelia; Hu, Min; Yao, Jun; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen, Haiyan; Carrasco, Daniel; Richardson, Andrea; Violette, Shelia; Gelman, Rebecca S.; Bissell, Mina J.; Schnitt, Stuart; Polyak, Kornelia

    2008-05-07

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  17. Breast metastasis from vaginal cancer.

    Science.gov (United States)

    Chandrasekaran, Neeraja; Scharifker, Daniel; Varsegi, George; Almeida, Zoyla

    2016-01-01

    Vaginal cancer is a rare malignancy accounting for 1-2% of all pelvic neoplasms. Dissemination usually occurs through local invasion and rarely metastasises to distal locations. Metastasis of vaginal cancer to the breast is extremely infrequent and unique. A 66-year-old Asian woman presented with vaginal bleeding and was found to have a vaginal mass and a left breast mass. Pathological assessment of the biopsies revealed identical squamous cell characteristics of both masses. We describe a very rare and novel case of a distally located vaginal carcinoma with metastasis to the breast Federation of Gynecology and Obstetrics (FIGO) stage IV (FIGO IVB). Robot-assisted extrafascial total hysterectomy with local vaginal mass excision and partial mastectomy of the left breast were performed. After surgery, the patient underwent adjuvant chemotherapy followed by breast and pelvic radiotherapy, with maintained complete remission after 3 years of follow-up. This combination of findings and treatment is very distinct with a unique and favourable response. PMID:27444140

  18. The prognostic significance of STAT3 in invasive breast cancer: analysis of protein and mRNA expressions in large cohorts.

    Science.gov (United States)

    Aleskandarany, Mohammed A; Agarwal, Devika; Negm, Ola H; Ball, Graham; Elmouna, Ahmed; Ashankyty, Ibraheem; Nuglozeh, Edem; Fazaludeen, Mohammad F; Diez-Rodriguez, Maria; Nolan, Christopher C; Tighe, Patrick J; Green, Andrew R; Ellis, Ian O; Rakha, Emad A

    2016-02-01

    Signal transducer and activator of transcription (STAT) transcription factors family are involved in diverse cellular biological functions. Reports regarding the prognostic impact of STAT3 expression in breast cancer (BC) are variable whether being a factor of poor or good prognosis. Immunohistochemical expression of phospho-STAT3 (pSTAT3) was studied in large series of invasive BC (n = 1270). pSTAT3 and STAT3 were quantified using reverse phase protein array (RPPA) on proteins extracted from macro-dissected FFPE tissues (n = 49 cases). STAT3 gene expression in the METABRIC cohort was also investigated. STAT3 gene expression prognostic impact was externally validated using the online BC gene expression data (n = 26 datasets, 4.177 patients). pSTAT3 was expressed in the nuclei and cytoplasm of invasive BC cells. Nuclear pSTAT3 overexpression was positively associated with smaller tumour size, lower grade, good NPI, negative lymphovascular invasion (LVI), ER+, PgR+, p53-, HER2-, and low Ki67LI and an improved breast cancer-specific survival (BCSS), independently of other factors. On RPPA, the mean pSTAT3 and STAT3 expressions were higher in ER+, PgR+, and smaller size tumours. Higher STAT3 transcripts in the METABRIC cohort were observed in cases with favourable prognostic criteria and as well as improved BCSS within the whole cohort, ER+ cohort with and without hormonal therapy, and ER- cohort including those who did not receive adjuvant chemotherapy. Pooled STAT3 gene expression data in the external validation cohort showed an association with improved patients' outcome (P < 0.001, HR = 0.84, 95 % CI 0.79-0.90). Results of this study suggest nuclear localisation of pSTAT3 as favourable prognostic marker in invasive BC, results re-enforced by analysis of STAT3 gene expression data. This good prognostic advantage was maintained in patients who received and who did not receive adjuvant therapy. Therefore, STAT3 could have context-dependent molecular roles of in BC

  19. Luteolin 8-C-β-fucopyranoside inhibits invasion and suppresses TPA-induced MMP-9 and IL-8 via ERK/AP-1 and ERK/NF-κB signaling in MCF-7 breast cancer cells.

    Science.gov (United States)

    Park, Su-Ho; Kim, Jung-Hee; Lee, Dong-Hun; Kang, Jeong-Woo; Song, Hyuk-Hwan; Oh, Sei-Ryang; Yoon, Do-Young

    2013-11-01

    Matrix metalloproteinase 9 (MMP-9) and interleukin-8 (IL-8) play major roles in tumor progression and invasion of breast cancer cells. The present study was undertaken to investigate the inhibitory mechanism of cell invasion by luteolin 8-C-β-fucopyranoside (named as LU8C-FP), a C-glycosylflavone, in human breast cancer cells. We investigated whether LU8C-FP would inhibit MMP-9 activation and IL-8 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 breast cancer cells. LU8C-FP suppressed TPA-induced MMP-9 and IL-8 secretion and mRNA expression via inhibition of the MAPK signaling pathway and down-regulation of nuclear AP-1 and NF-κB. TPA-induced phosphorylation of ERK 1/2 was suppressed by LU8C-FP, whereas JNK and p38 MAPK phosphorylation were unaffected. In addition, LU8C-FP blocked the ERK 1/2 pathways following expression of MMP-9 and IL-8. These results suggest LU8C-FP may function to suppress invasion of breast cancer cells through the ERK/AP-1 and ERK/NF-κB signaling cascades.

  20. The diagnosis and management of pre-invasive breast disease: Genetic alterations in pre-invasive lesions

    International Nuclear Information System (INIS)

    The development of modern molecular genetic techniques has allowed breast cancer researchers to clarify the multistep model of breast carcinogenesis. Laser capture microdissection coupled with comparative genomic hybridisation and/or loss-of-heterozygosity methods have confirmed that many pre-invasive lesions of the breast harbour chromosomal abnormalities at loci known to be altered in invasive breast carcinomas. Current data do not provide strong evidence for ductal hyperplasia of usual type as a precursor lesion, although some are monoclonal proliferations; however, atypical hyperplasia and in situ carcinoma appear to be nonobligate precursors. We review current knowledge and the contribution of molecular genetics in the understanding of breast cancer precursors and pre-invasive lesions

  1. Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation of p53-miR34a axis.

    Science.gov (United States)

    Avtanski, Dimiter B; Nagalingam, Arumugam; Tomaszewski, Joseph E; Risbood, Prabhakar; Difillippantonio, Michael J; Saxena, Neeraj K; Malhotra, Sanjay V; Sharma, Dipali

    2016-08-01

    The tumor suppressor p53 plays a critical role in suppressing cancer growth and progression and is an attractive target for the development of new targeted therapies. We synthesized several indolo-pyrido-isoquinolin based alkaloids to activate p53 function and examined their therapeutic efficacy using NCI-60 screening. Here, we provide molecular evidence that one of these compounds, 11-methoxy-2,3,4,13-tetrahydro-1H-indolo[2',3':3,4]pyrido[1,2-b]isoquinolin-6-ylium-bromide (termed P18 or NSC-768219) inhibits growth and clonogenic potential of cancer cells. P18 treatment results in downregulation of mesenchymal markers and concurrent upregulation of epithelial markers as well as inhibition of migration and invasion. Experimental epithelial-mesenchymal-transition (EMT) induced by exposure to TGFβ/TNFα is also completely reversed by P18. Importantly, P18 also inhibits mammosphere-formation along with a reduction in the expression of stemness factors, Oct4, Nanog and Sox2. We show that P18 induces expression, phosphorylation and accumulation of p53 in cancer cells. P18-mediated induction of p53 leads to increased nuclear localization and elevated expression of p53 target genes. Using isogenic cancer cells differing only in p53 status, we show that p53 plays an important role in P18-mediated alteration of mesenchymal and epithelial genes, inhibition of migration and invasion of cancer cells. Furthermore, P18 increases miR-34a expression in p53-dependent manner and miR-34a is integral for P18-mediated inhibition of growth, invasion and mammosphere-formation. miR-34a mimics potentiate P18 efficacy while miR-34a antagomirs antagonize P18. Collectively, these data provide evidence that P18 may represent a promising therapeutic strategy for the inhibition of growth and progression of breast cancer and p53-miR-34a axis is important for P18 function. PMID:27259808

  2. Can the addition of regional radiotherapy counter-balance important risk factors in breast cancer patients with extracapsular invasion of axillary lymph-node metastases?

    International Nuclear Information System (INIS)

    Purpose: To evaluate if locoregional radiotherapy (RT) versus local irradiation only can alter the pattern of failure in breast cancer patients with extranodal invasion. Patients and Methods: From 08/1988 to 06/1998, 81 patients with extranodal invasion were treated with adjuvant RT (median total dose: 50.4 Gy), 46/81 only locally, 35/81 locoregionally due to presumed adverse parameters. The mean number of resected (positive) lymph nodes was 17 (seven). 78 patients received adjuvant systemic treatment(s). Results: Patients treated with locoregional RT had significantly more often lymphatic vessel invasion (LVI; 63% vs. 28%; p = 0.003), T3/T4 tumors (43% vs. 17%; p = 0.014), and four or more positive lymph nodes (91% vs. 46%; p < 0.001) than patients irradiated only locally. Disease progression occurred in 24/81 patients (locoregional RT: 26% vs. local RT: 33%). The above risk factors were highly significant of worse outcome. Despite their overrepresentation in the locoregional RT group, no difference was found between both groups in regard to disease-free survival (DFS; p = 0.83) and overall survival (OS; p = 0.56), suggesting that regional RT was able to counterbalance the increased risk. There was even a trend toward a better 3-year DFS, 61% in locoregional RT and 37% in local RT, in the subgroup of patients with four or more positive lymph nodes. In a Cox regression model, higher T-stage, four or more positive lymph nodes, and LVI remained significant. For DFS and distant metastasis-free survival (DMFS), the absence of estrogen receptors and the omission of regional RT were also significant. Conclusion: Our data suggest that the addition of regional RT might be beneficial in selected subgroups of patients with extranodal invasion and other poor prognostic factors. (orig.)

  3. Viruses and Breast Cancer

    Directory of Open Access Journals (Sweden)

    James S. Lawson

    2010-04-01

    Full Text Available Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

  4. Viruses and Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, James S., E-mail: james.lawson@unsw.edu.au; Heng, Benjamin [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney (Australia)

    2010-04-30

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

  5. Viruses and Breast Cancer

    International Nuclear Information System (INIS)

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix

  6. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis

    International Nuclear Information System (INIS)

    Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a vital transcription factor that regulates multiple important biological processes, including the epithelial–mesenchymal transition (EMT) and metastasis of breast cancer. Sinomenine is an isoquinoline well known for its remarkable curative effect on rheumatic and arthritic diseases and can induce apoptosis of several cancer cell types. Recently, sinomenine was reported as a tumor suppressor via inhibiting cell proliferation and inducing apoptosis. However, the role and mechanism of sinomenine in invasion and metastasis of breast cancer are largely unknown. Here, we report that sinomenine suppressed the invasion and migration of MDA-MB-231 and 4T1 breast cancer cells in a dose-dependent manner. We detected binding of NF-κB to the inhibitor of NF-κB (IκB) after the MDA-MB-231 cells were treated with 0.25, 0.5, and 1 mM sinomenine. Co-IP analysis revealed that sinomenine enhanced the binding of NF-κB and IκB in a dose-dependent manner, suggesting that sinomenine had an effect on inactivation of NF-κB. Western blotting and ELISA approaches indicated that the suppression effect was closely associated with the phosphorylation of IκB kinase (IKK) and its negative regulator CUEDC2. Sinomenine treatment decreased miR-324-5p expression, thus increased the level of its target gene CUEDC2, and then blocked the phosphorylation of IKK through altering the upstream axis. Finally, transfection of a miR-324-5p mimic inhibited the suppression of invasion and metastasis of MDA-MB-231 and 4T1 cell by sinomenine, providing evidence that sinomenine treatment suppressed breast cancer cell invasion and metastasis via regulation of the IL4/miR-324-5p/CUEDC2 axis. Our findings reveal a novel mechanism by which sinomenine suppresses cancer cell invasion and metastasis, i.e., blocking NF-κB activation. - Highlights: • Sinomenine reduced invasion and migration of MDA-MB-231 and 4T1 breast cancer cells.

  7. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis

    Energy Technology Data Exchange (ETDEWEB)

    Song, Lingqin, E-mail: qinlingsongxa@163.com [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China); Liu, Di; Zhao, Yang [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China); He, Jianjun [Department of Surgical Oncology, The First Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710061 (China); Kang, Huafeng; Dai, Zhijun; Wang, Xijing; Zhang, Shuqun; Zan, Ying [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China)

    2015-08-28

    Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a vital transcription factor that regulates multiple important biological processes, including the epithelial–mesenchymal transition (EMT) and metastasis of breast cancer. Sinomenine is an isoquinoline well known for its remarkable curative effect on rheumatic and arthritic diseases and can induce apoptosis of several cancer cell types. Recently, sinomenine was reported as a tumor suppressor via inhibiting cell proliferation and inducing apoptosis. However, the role and mechanism of sinomenine in invasion and metastasis of breast cancer are largely unknown. Here, we report that sinomenine suppressed the invasion and migration of MDA-MB-231 and 4T1 breast cancer cells in a dose-dependent manner. We detected binding of NF-κB to the inhibitor of NF-κB (IκB) after the MDA-MB-231 cells were treated with 0.25, 0.5, and 1 mM sinomenine. Co-IP analysis revealed that sinomenine enhanced the binding of NF-κB and IκB in a dose-dependent manner, suggesting that sinomenine had an effect on inactivation of NF-κB. Western blotting and ELISA approaches indicated that the suppression effect was closely associated with the phosphorylation of IκB kinase (IKK) and its negative regulator CUEDC2. Sinomenine treatment decreased miR-324-5p expression, thus increased the level of its target gene CUEDC2, and then blocked the phosphorylation of IKK through altering the upstream axis. Finally, transfection of a miR-324-5p mimic inhibited the suppression of invasion and metastasis of MDA-MB-231 and 4T1 cell by sinomenine, providing evidence that sinomenine treatment suppressed breast cancer cell invasion and metastasis via regulation of the IL4/miR-324-5p/CUEDC2 axis. Our findings reveal a novel mechanism by which sinomenine suppresses cancer cell invasion and metastasis, i.e., blocking NF-κB activation. - Highlights: • Sinomenine reduced invasion and migration of MDA-MB-231 and 4T1 breast cancer cells.

  8. Getting free of breast cancer

    DEFF Research Database (Denmark)

    Halttunen, Arja; Hietanen, P; Jallinoja, P;

    1992-01-01

    Twenty-two breast cancer patients who were relapse-free and had no need for cancer-related treatment were interviewed 8 years after mastectomy in order to evaluate their feelings of getting free of breast cancer and the meaning of breast cancer in their lives. The study is a part of an intervention...... and follow-up study of 57 breast cancer patients. Half of the 22 patients still had frequent or occasional thoughts of recurrence and over two-thirds still thought they had not been 'cured' of cancer. More than half of the patients admitted that going through breast cancer had made them more mature. Women...

  9. Breast cancer statistics and markers

    OpenAIRE

    Mallika Siva Donepudi; Kasturi Kondapalli; Seelam Jeevan Amos; Pavithra Venkanteshan

    2014-01-01

    Breast cancer is one of the familiar diseases in women. Incidence and mortality due to cancer, particularly breast cancer has been increasing for last 50 years, even though there is a lacuna in the diagnosis of breast cancer at early stages. According to World Health Organization (WHO) 2012 reports, breast cancer is the leading cause of death in women, accounting 23% of all cancer deaths. In Asia, one in every three women faces the risk of breast cancer in their lifetime as per reports of WHO...

  10. Breast Cancer Detection

    Science.gov (United States)

    2000-01-01

    The BioScan System was developed by OmniCorder Technologies, Inc. at the Jet Propulsion Laboratory. The system is able to locate cancerous lesions by detecting the cancer's ability to recruit a new blood supply. A digital sensor detects infrared energy emitted from the body and identifies the minute differences accompanying the blood flow changes associated with cancerous cells. It also has potential use as a monitoring device during cancer treatment. This technology will reduce the time taken to detect cancerous cells and allow for earlier intervention, therefore increasing the overall survival rates of breast cancer patients.

  11. Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

    OpenAIRE

    Yubing Xie; Bridget M. Mooney; Nurazhani Abdul Raof

    2011-01-01

    Breast cancer is the most prevalent disease amongst women worldwide and metastasis is the main cause of death due to breast cancer. Metastatic breast cancer cells and embryonic stem (ES) cells display similar characteristics. However, unlike metastatic breast cancer cells, ES cells are nonmalignant. Furthermore, embryonic microenvironments have the potential to convert metastatic breast cancer cells into a less invasive phenotype. The creation of in vitro embryonic microenvironments will enab...

  12. Adipocytokines and breast cancer risk

    Institute of Scientific and Technical Information of China (English)

    HOU Wei-kai; XU Yu-xin; YU Ting; ZHANG Li; ZHANG Wen-wen; FU Chun-li; SUN Yu; WU Qing; CHEN Li

    2007-01-01

    Background Many researches suggested that obesity increased the risk of breast cancer, but the mechanism was currently unknown. Adipocytokines might mediate the relationship. Our study was aimed to investigate the relationship between serum levels of resistin, adiponectin and leptin and the onset, invasion and metastasis of breast cancer.Methods Blood samples were collected from 80 newly diagnosed, histologically confirmed breast cancer patients and 50 age-matched healthy controls. Serum levels of resistin, adiponectin and leptin were determined by enzyme-linked immunosorbent assays (ELISA); fasting blood glucose (FBG), lipids, body mass index (BMI), and waist circumference (WC) were assayed simultaneously.Results Serum levels of adiponectin ((8.60±2.92) mg/L vs (10.37±2.81) mg/L, P=0.001) and HDL-c were significantly decreased in breast cancer patients in comparison to controls. Serum levels of resistin ((26.35±5.36) μg/L vs (23.32±4.75)μg/L, P=0.000), leptin ((1.35±0.42) μg/L vs (1.06±0.39) μg/L, P=0.003), FBG and triglyceride (TG) in breast cancer patients were increased in contrast to controls, respectively. However, we did not find the significant difference of the serum levels of resistin, adiponectin and leptin between premenopausal breast cancer patients and healthy controls (P=0.091, 0.109 and 0.084, respectively). The serum levels of resistin, adiponectin and leptin were significantly different between patients with lymph node metastasis (LNM) and those without LNM (P=0.001, 0.000 and 0.006, respectively).The stepwise regression analysis indicated that the tumor size had the close correlation with leptin (R2=0.414, P=0.000)and FBG (R2=0.602, P=0.000). Logistic regression analysis showed that reduced serum levels of adiponectin (OR:0.805;95%CI: 0.704-0.921; P=0.001), HDL (OR: 0.087; 95%CI: 0.011-0.691, P=0.021), elevated leptin (OR:2.235;95%CI:1.898-4.526; P=0.004) and resistin (OR: 1.335; 95%CI: 1.114-2.354; P=0.012) increased the risk for

  13. Life After Breast Cancer Treatment

    Science.gov (United States)

    FACTS FOR LIFE Life After Breast Cancer Treatment Once breast cancer treatment ends, you may face a new set of issues and concerns. ... fear. If fear starts to disrupt your daily life, talk to your doctor. Getting the support and ...

  14. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... inhibitor, can do an even better job of preventing breast cancer than the SERMs. Aromatase inhibitors stop an enzyme ...

  15. Vitamin D and Breast Cancer

    OpenAIRE

    Shao, Theresa; Klein, Paula; Grossbard, Michael L.

    2012-01-01

    Vitamin D metabolism and its mechanism of action, the current evidence on the relationship between vitamin D and breast cancer, and the optimal dosing of vitamin D for breast cancer prevention are summarized.

  16. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID:27390604

  17. Breast cancer surgery in elderly patients: postoperative complications and survival

    OpenAIRE

    Rocco, Nicola; Rispoli, Corrado; Pagano, Gennaro; Rengo, Giuseppe; Compagna, Rita; Danzi, Michele; Accurso, Antonello; Amato, Bruno

    2013-01-01

    Aims and background Old age is associated with comorbidity and decreased functioning which influences treatment decisions in elderly breast cancer patients. The purpose of this study was to identify risk factors for complications after breast cancer surgery in elderly patients, and to assess mortality in patients with postoperative complications. Methods We retrospectively considered all female patients aged 65 years and older with invasive and in situ breast cancer who were diagnosed and tre...

  18. Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes.

    Directory of Open Access Journals (Sweden)

    I-Hsuan Lin

    Full Text Available Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs and the hypomethylation of the megabase-sized partially methylated domains (PMDs are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation.

  19. Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy

    International Nuclear Information System (INIS)

    Axillary node status after induction chemotherapy for locally advanced breast cancer has been shown on multivariate analysis to be an independent predictor of relapse. However, it has been postulated that responders to induction chemotherapy with a clinically negative axilla could be spared the burden of lymphadenectomy, because most of them will not show histological nodal invasion. P-glycoprotein expression in the rescue mastectomy specimen has finally been identified as a significant predictor of patient survival. We studied the expression of the genes encoding multidrug resistance associated protein (MDR1) and lung cancer associated resistance protein (LRP) in formalin-fixed, paraffin-embedded tumor samples from 52 patients treated for locally advanced breast cancer by means of induction chemotherapy followed by rescue mastectomy. P-glycoprotein expression was assessed by means of immunohistochemistry before treatment in 23 cases, and by means of reverse-transcriptase-mediated polymerase chain reaction (RT-PCR) after treatment in 46 (6 failed). LRP expression was detected by means of immunohistochemistry, with the LRP-56 monoclonal antibody, in 31 cases before treatment. Immunohistochemistry for detecting the expression of c-erb-B2, p53, Ki67, estrogen receptor and progesterone receptor are routinely performed in our laboratory in every case, and the results obtained were included in the study. All patients had received between two and six cycles of standard 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy, with two exceptions [one patient received four cycles of a docetaxel-adriamycin combination, and the other four cycles of standard cyclophosphamide-methotrexate-5-fluorouracil (CMF) polychemotherapy]. Response was assessed in accordance with the Response Evaluation Criteria In Solid Tumors (RECIST). By these, 2 patients achieved a complete clinical response, 37 a partial response, and the remaining 13 showed stable disease. This makes a

  20. Gli1 enhances migration and invasion via up-regulation of MMP-11 and promotes metastasis in ERα negative breast cancer cell lines

    OpenAIRE

    Kwon, Yeon-Jin; Douglas R Hurst; Steg, Adam D.; Yuan, Kun; Vaidya, Kedar. S.; Welch, Danny R.; Frost, Andra R.

    2011-01-01

    Gli1 is an established oncogene and its expression in Estrogen Receptor (ER) α negative and triple negative breast cancers is predictive of a poor prognosis; however, the biological functions regulated by Gli1 in breast cancer have not been extensively evaluated. Herein, Gli1 was over-expressed or down-regulated (by RNA interference and by expression of the repressor form of Gli3) in the ERα negative, human breast cancer cell lines MDA-MB-231 and SUM1315. Reduced expression of Gli1 in these t...

  1. Protocadherin-7 induces bone metastasis of breast cancer

    International Nuclear Information System (INIS)

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

  2. Protocadherin-7 induces bone metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-05

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

  3. Histopathological Features of Invasion of Breast Invasive Ductal Carcinoma and Safety of Breast-conserving Surgery

    Institute of Scientific and Technical Information of China (English)

    Chunping LIU; Huaxiong PAN; Zhi LI; Lan SHI; Tao HUANG

    2009-01-01

    In order to investigate the relationship between the extent of tumor invasion and the tu-mor size,axillary lymph nodes metastasis,Her-2 gene overexpression,and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery,the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed.The correlation analysis on invasive extent,which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre,and the tumor size,axillary lymph nodes metastasis,Her-2 gene overexpression,and his-tologic grading was processed.There was a significant correlation between invasive extent and tumor size (r=0.766,P0.05),and histologic grading (r=0.228,P>0.05).The 100% negative rate of infiltration in patients without nipple discharge with tumor size 3 cm was obtained at 1.5,2.0 and 2.5 cm away from the tumor respectively.It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.

  4. Oncogenic Pathways in Lobular Breast Cancer

    NARCIS (Netherlands)

    Ercan, C.

    2012-01-01

    Breast cancer affects approximately 1 in 8 women in the Western world with more than one million new cases worldwide per year, of which 30% will eventually die. It is a heterogeneous disease with several histological and molecular characteristics within tumors and between patients. Invasive lobular

  5. Bilateral breast cancer, synchronous and metachronous; differences and outcome

    NARCIS (Netherlands)

    Jobsen, J.J.; Palen, van der J.; Ong, F.; Riemersma, S.; Struikmans, H.

    2015-01-01

    The aims of this study were twofold: to analyze the incidence of patients having synchronous or metachronous bilateral invasive breast cancer (SBBC and MBBC) and to assess the characteristics and outcome compared to those having unilateral breast cancer (UBC). The used data were obtained from our pr

  6. Breast cancer screening

    OpenAIRE

    Skrabanek, P

    1988-01-01

    Consensus is still lacking on guidelines for breast-cancer screening with mammography: who should be screened, how frequently at what age, to what benefits and at what risks. American, Dutch, Swedish and Italian studies spanning the 1960s to the 1980s reveal a benefit from screening (reduced mortality from breast cancer) that occurs unambiguously only in women 50 years of age and over. Physicians who choose to screen mammographically their over-49-year-old female patients must do so with the ...

  7. The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion.

    Science.gov (United States)

    Mady, Mohamed S; Mohyeldin, Mohamed M; Ebrahim, Hassan Y; Elsayed, Heba E; Houssen, Wael E; Haggag, Eman G; Soliman, Randa F; El Sayed, Khalid A

    2016-01-15

    Fungi of the genus Penicillium produce unique and chemically diverse biologically active secondary metabolites, including indole alkaloids. The role of dysregulated hepatocyte growth factor (HGF) and its receptor, c-Met, in the development and progression of breast carcinoma is documented. The goal of this work is to explore the chemistry and bioactivity of the secondary metabolites of the endophytic Penicillium chrysogenum cultured from the leaf of the olive tree Olea europea, collected in its natural habitat in Egypt. This fungal extract showed good inhibitory activities against the proliferation and migration of several human breast cancer lines. The CH2Cl2 extract of P. chrysogenum mycelia was subjected to bioguided chromatographic separation to afford three known indole alkaloids; meleagrin (1), roquefortine C (2) and DHTD (3). Meleagrin inhibited the growth of the human breast cancer cell lines MDA-MB-231, MDA-468, BT-474, SK BR-3, MCF7 and MCF7-dox, while similar treatment doses were found to have no effect on the growth and viability of the non-tumorigenic human mammary epithelial cells MCF10A. Meleagrin also showed excellent ATP competitive c-Met inhibitory activity in Z-Lyte assay, which was further confirmed via molecular docking studies and Western blot analysis. In addition, meleagrin treatment caused a dose-dependent inhibition of HGF-induced cell migration, and invasion of breast cancer cell lines. Meleagrin treatment potently suppressed the invasive triple negative breast tumor cell growth in an orthotopic athymic nude mice model, promoting this unique natural product from hit to a lead rank. The indole alkaloid meleagrin is a novel lead c-Met inhibitory entity useful for the control of c-Met-dependent metastatic and invasive breast malignancies. PMID:26692349

  8. CYTOKINE-PRODUCING RESERVE OF IMMUNOCOMPETENT CELLS FROM BLOOD AND INVASIVE DUCTAL BREAST CANCER TISSUES: ITS CORRELATION WITH HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL PARAMETERS OF MALIGNANT NEOPLASIA

    Directory of Open Access Journals (Sweden)

    S. A. Arkhipov

    2016-01-01

    Full Text Available The aim of the study was to investigate a relationship between cytokine-producing reserve of invasive ductal cancer cells and its microenvironment, and cytokine-producing reserve of immunocompetent blood cells (IBC, as well as with histopathological and immunohistochemical characteristics of breast cancer. Using ELISA method we investigated the spontaneous and stimulated with polyclonal activators (PA cytokine-producing reserve of IBC and biopsy specimens from invasive ductal cancer (adenocarcinoma in 34 women. Appropriate values were expressed by the Influence Index of polyclonal activators (IIPA upon cytokine production (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1ra, TNFα, IFNγ, G-CSF, GM-CSF, VEGF-A, MCP-1. In tumor biopsies, we studied expression of VEGF-A, estrogen receptor, progesteron receptor and pro-proliferation marker Ki-67 by means of immunohistochemical method. Activation values of blood IBC in most cases, except of IL-18, IL-1β and MCP-1, were higher than appropriate effects upon cytokine production by tumor tisuues. Meanwhile, the IIPA activation index upon IL-18 (a proinflammatory and prooncogene cytokine production by tumor cells and its microenvironment proved to be elevated, as compared to appropriate IIPA by the blood IBC. Statistical studies showed a direct correlation between IIPA and cytokine production in tumor supernates, IIPA of VEGF-A expression in tumor tissue, with pathohistological parameters and expression of estrogen and progesterone receptors and Ki-67 proliferation marker. A high positive correlation was obtained between IIPA TNFα production by the tumor tissue, and degree of tumor vascularization.We have revealed a negative correlation between IIPA for IL-6, MCP-1 and Ki-67 marker of cell proliferation. A direct correlation was found between IIPA values for IL-1ra/IL-1β production ratios in blood cells, and IIPA for VEGF-A expression in adenocarcinoma tissues, thus indicating to probable

  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. [Breast cancer update].

    Science.gov (United States)

    Armuss, A

    2014-06-01

    Breast Cancer, with a life-time prevalence of about 10-12%, is the most common cancer in women. In 2013, the actress Angelina Jolie, by announcing she had a double mastectomy, increased the awareness of a family history of breast and ovarian cancer and the treatment available to reduce the inherited risks. In Germany, each year about 25 out of 100,000 women (age-standardized according to European Standard) die of the disease. The number of newly diagnosed cases is about 72,000 per year. In comparison, many other countries record higher levels. Investing in the development of new therapies has therefore been key for many years. Prevention programs, such as the mammography screening are publicly touted, in both cases with the aim to reduce breast cancer mortality. To accurately assess the risk in underwriting, it is important to know about the risk factors for the development of breast cancer, as well as the latest advances in prevention, therapy and their prognostic classification. The following article provides an overview. PMID:25000626

  11. Associations of Breast Cancer Risk Factors With Tumor Subtypes : A Pooled Analysis From the Breast Cancer Association Consortium Studies

    NARCIS (Netherlands)

    Yang, Xiaohong R.; Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomaeki, Kristiina; Heikkilae, Paeivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J.; Van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O'Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M. S.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Doerk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Perez, Jose Ignacio; Menendez Rodriguez, Primitiva; Zamora, Pilar; Bentez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Bruening, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collee, Margriet; Wang-Gohrke, Shan; Pylkaes, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Paeivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Orsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Borge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; Mckay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P. E. A.; Tollenaar, R. A. E. M.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients f

  12. Contemporary risks of local and regional recurrence and contralateral breast cancer in patients treated for primary breast cancer

    NARCIS (Netherlands)

    Aalders, K. C.; Van Bommel, A. C M; Van Dalen, T.; Sonke, G. S.; Van Diest, P. J.; Boersma, L. J.; Van Der Heiden-Van Der Loo, M.

    2016-01-01

    Introduction Breast cancer treatment has evolved extensively over the past two decades with a shift towards less invasive local treatment and increased systemic treatment. The present study aimed to investigate the rates of local (LR) and regional (RR) recurrence and contralateral breast cancer (CBC

  13. Prediction of Extracapsular Invasion at Metastatic Sentinel Nodes and Non-sentinel Lymph Nodal Metastases by FDG-PET in Cases with Breast Cancer.

    Science.gov (United States)

    Fujii, Takaaki; Yajima, Reina; Tatsuki, Hironori; Kuwano, Hiroyuki

    2016-04-01

    We have previously reported that the presence of an extracapsular invasion (ECI) at sentinel lymph nodes (SLNs) is a strong predictor of non-SLN metastasis in breast cancer. We hypothesized that(18)F-fluorodeoxyglucose (FDG) uptake by metastatic SLNs reflects invasive disease, or ECI. In this study, we evaluated the association of FDG uptake with ECI on SLNs and the possibility of FDG-positron-emission tomography (PET) assessment of axillary non-SLN metastases. We retrospectively investigated the cases of 156 consecutive patients with primary breast cancer who underwent SLN biopsy and FDG-PET preoperatively. Among 35 patients (22.4%) in whom the presence of SLN metastases was diagnosed, 10 cases (28.6%) had FDG uptake in the axillary lesion. The sensitivity, specificity, overall accuracy, and false-negative rates in the diagnosis of SLN status by FDG-PET were 28.6%, 99.2%, 83.3%, and 71.4%, respectively. The false-positive rate of FDG-PET evaluation was 0.8%. The 35 cases with lymph node metastases were divided into two groups based on the presence of FDG uptake in the axillary lesions. None of the clinicopathological features of the primary tumor were significantly associated with FDG uptake in the axillary lesion. The present analysis revealed that only tumor size of the metastatic lymph node was significantly associated with FDG uptake in the axillary lesion. The two groups were not significantly different in terms of presence of ECI and non-SLN metastasis. Among the 35 cases with SLN metastases, 13 cases (37.1%) had non-SLN metastasis. Only ECI was a predictor of non-SLN involvement. FDG uptake in the axilla was not associated with non-SLN metastasis in this study. In conclusion, FDG-PET evaluation of lymph nodes is not a sufficient indicator of ECI at SLN metastasis or non-SLN metastasis, suggesting that axillary lymph node dissection cannot be avoided. However, since the positive predictive value for SLN metastasis is high, positive FDG uptake in the axillary

  14. Does Aluminium Trigger Breast Cancer?

    OpenAIRE

    Peter Jennrich; Claus Schulte-Uebbing

    2016-01-01

    Summary. Breast cancer is by far the most common cancer in women in the western world. In 90% of breast cancers, environmental factors are among the causes. The frequency with which the tumour occurs in the outer upper part of the breast has risen with above average rates in recent decades. Aluminium salts as ingredients in deodorants and antiperspirants are being absorbed by the body to a greater extent than hitherto assumed. Their toxicity for healthy and diseased breast tissue cells includ...

  15. 放射治疗在浸润性乳腺癌保乳术中的进展和争议%Progress and Controversies:radiation therapy for invasive breast cancer of breast-conserving surgery

    Institute of Scientific and Technical Information of China (English)

    李学波; 陈湘磊; 张士义

    2015-01-01

    Radiation therapy is a critical component of the multidisciplinary management of invasive breast cancer . In appropriately selected patients ,radiation not only improves local control and distress of local recurrence ,but also improves survival by preventing seeding and reseeding .This article reviews the role of radiation therapy in invasive breast cancer management after breast‐conserving surgery .It focuses on emerging evidence that helps to define the clinical situations in which radiotherapy is indicated ,the appropriate targets of treatment ,and optimal approaches for minimizing the toxicity . It includes a discussion of new approaches ,including hypofractionation and intensity modulation ,as well as a discussion of promising avenues for future research .%放射治疗是浸润性乳腺癌保乳术综合治疗的重要组成部分之一,选取恰当的患者术后给予局部放疗,不但可以有效降低局部复发率,而且可以降低远处转移率和提高生存率。本综述回顾性探讨放射治疗在浸润性乳腺癌保乳术中的应用,选择合适的放疗方法,降低毒副作用,获得最佳的治疗目的,并总结了新的放疗方法:低分割放疗和调强放疗,对不同病例的治疗情况,同时还探讨了保乳术后放疗的争议。希望本综述能为以后的临床工作和研究指引方向。

  16. Alcohol and breast cancer tumor subtypes in a Spanish Cohort.

    Science.gov (United States)

    Gago-Dominguez, Manuela; Castelao, J Esteban; Gude, Francisco; Fernandez, Maite Peña; Aguado-Barrera, Miguel E; Ponte, Sara Miranda; Redondo, Carmen M; Castelo, Manuel Enguix; Dominguez, Alejandro Novo; Garzón, Víctor Muñoz; Carracedo, Angel; Martínez, María Elena

    2016-01-01

    Although alcohol intake is an established risk factor for overall breast cancer, few studies have looked at the relationship between alcohol use and breast cancer risk by the four major subtypes of breast cancer and very few data exist in the alcohol-breast cancer relationship in Spanish women. A population-based case-control study was conducted in Galicia, Spain. A total of 1766 women diagnosed with invasive breast cancer between 1997 and 2014 and 833 controls participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics were collected. We examined the alcohol-breast cancer association according to the major breast cancer subtypes [hormone-receptor-positive, HER2-negative (luminal A); hormone-receptor-positive, HER2-positive (luminal B); hormone-receptor-negative, HER2-negative (TNBC); and hormone-receptor-negative, HER2-positive (HER2 overexpressing)] as well as grade and morphology in Spanish women. With the exception of HER2 overexpressing, the risk of all subtypes of breast cancer significantly increased with increasing alcohol intake. The association was similar for hormonal receptor positive breast cancer, i.e., luminal A and luminal B breast cancer (odds ratio, OR 2.16, 95 % confidence interval, CI 1.55-3.02; and OR 1.98, 95 % CI 1.11-3.53, respectively), and for TNBC (TNBC: OR 1.93, 95 % CI 1.07-3.47). The alcohol-breast cancer association was slightly more pronounced among lobular breast cancer (OR 2.76, 95 % CI 1.62-4.69) than among ductal type breast cancers (OR 2.21, 95 % CI 1.61-3.03). In addition, significant associations were shown for all grades, I, II and III breast cancer (OR 1.98, 95 % CI 1.26-3.10; OR 2.34, 95 % CI 1.66-3.31; and OR 2.16, 95 % CI 1.44-3.25 for Grades I, II and III, respectively). To our knowledge, this is the first study to examine the association of breast cancer subtypes and alcohol intake in Spanish women. Our findings indicate that breast cancer risk increased

  17. ShRNA-mediated gene silencing of MTA1 influenced on protein expression of ER alpha, MMP-9, CyclinD1 and invasiveness, proliferation in breast cancer cell lines MDA-MB-231 and MCF-7 in vitro

    Directory of Open Access Journals (Sweden)

    Zhang Ping

    2011-05-01

    Full Text Available Abstract Background MTA1(metastasis associated-1 is a tumor metastasis associated candidate gene and overexpression in many human tumors, including breast cancer. In this study, we investigated depressive effect on MTA1 by MTA1-specific short hairpin RNA(shRNA expression plasmids in human breast cancer cell lines MDA-MB-231 and MCF-7, and effect on protein levels of ER alpha, MMP-9, cyclinD1, and tumor cell invasion, proliferation. Methods ShRNA expression vectors targeting MTA1 was constructed and transfected into human breast cancer cell lines MDA-MB-231 and MCF-7. The transfection efficiency was evaluated by fluorescence microscopy, mRNA levels of MTA1 were detected by reverse transcription-polymerase chain reaction (RT-PCR, protein levels of ER alpha, MMP-9 and cyclinD1 were detected by Western blotting, respectively. Tumor cells invasive ability were evaluated by Boyden chamber assay, the cells proliferation were evaluated using cell growth curve and MTT analysis, the cell cycle analysis was performed using flow cytometry. Results Down-regulation of MTA1 by RNAi approach led to re-expression of ER alpha in ER-negative breast cancer cell lines MDA-MB-231, and reduced protein levels of MMP-9 and CyclinD1, as well as decreased tumor cell invasion and proliferation, more cells were blocked in G0/G1 stage(P 0.05. Conclusions ShRNA targeted against MTA1 could specifically mediate the MTA1 gene silencing and consequentially recover the protein expression of ER alpha, resulting in increase sensitivity of antiestrogens, as well as suppress the protein levels of MMP-9 and cyclinD1 in ER-negative human breast cancer cell lines MDA-MB-231. Silencing effect of MTA1 could efficiently inhibit the invasion and proliferation in MDA-MB-231 cells. The shRNA interference targeted against MTA1 may have potential therapeutic utility in human breast cancer.

  18. Breast Cancer - Early Diagnosis

    Centers for Disease Control (CDC) Podcasts

    2011-04-28

    This podcast answers a listener's question about how to tell if she has breast cancer.  Created: 4/28/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/28/2011.

  19. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie;

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight into the t......Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  20. Breast Cancer and Fatigue

    OpenAIRE

    Bardwell, Wayne A; Ancoli-Israel, Sonia

    2008-01-01

    Fatigue is a common and disabling symptom in breast cancer patients and survivors. A rather nebulous concept, fatigue overlaps with sleepiness and depressed mood. In this chapter, we cover methods for assessing fatigue; describe the occurrence of fatigue before, during and after initial treatment; present possible underlying mechanisms of fatigue; and, enumerate approaches to its treatment.

  1. Prostate cancer is not breast cancer

    Directory of Open Access Journals (Sweden)

    Ajit Venniyoor

    2016-01-01

    Full Text Available Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach.

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

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

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

  3. Ruptured gallbladder as the first presentation of breast cancer

    Directory of Open Access Journals (Sweden)

    Abdullah KE

    2009-06-01

    Full Text Available Abstract Background Perforation of the gall bladder as a first presentation of breast cancer has not been reported. Case presentation Here we present a case of an elderly lady with acute abdomen with evidence of possible perforation of gall bladder on CT scan. Histopathology of the cholecystectomy specimen revealed invasive lobular breast cancer. Her metastatic breast cancer with right sided primary discovered subsequent to her presentation with acute abdomen is managed successfully with Anastrozole. Conclusion We present a rare case of gall bladder perforation from metastatic breast cancer.

  4. Elevated expression of LSD1 (Lysine-specific demethylase 1 during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Serce Nuran

    2012-08-01

    Full Text Available Abstract Background Lysine-specific demethylase1 (LSD1 is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS in comparison to invasive ductal breast cancer (IDC. Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27, intermediate grade DCIS (n = 30, high grade DCIS (n = 31 and in invasive ductal breast cancer (n = 32. SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

  5. Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer

    Science.gov (United States)

    2016-06-23

    HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Breast Adenocarcinoma; Inflammatory Breast Carcinoma

  6. 3,5,4′-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/β-catenin signaling cascades and reversal of epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Jie-Heng [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan, ROC (China); Hsu, Li-Sung [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan, ROC (China); Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan, ROC (China); Lin, Chih-Li [Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, ROC (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan, ROC (China); Hong, Hui-Mei [Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan, ROC (China); Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402, Taiwan, ROC (China); Pan, Min-Hsiung [Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung 811, Taiwan, ROC (China); Way, Tzong-Der [Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung 40402, Taiwan, ROC (China); Chen, Wei-Jen, E-mail: cwj519@csmu.edu.tw [Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan, ROC (China); Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402, Taiwan, ROC (China)

    2013-11-01

    The molecular basis of epithelial–mesenchymal transition (EMT) functions as a potential therapeutic target for breast cancer because EMT may endow breast tumor-initiating cells with stem-like characteristics and enable the dissemination of breast cancer cells. We have recently verified the antitumor activity of 3,5,4′-trimethoxystilbene (MR-3), a naturally methoxylated derivative of resveratrol, in colorectal cancer xenografts via an induction of apoptosis. The effect of MR-3 on EMT and the invasiveness of human MCF-7 breast adenocarcinoma cell line were also explored. We found that MR-3 significantly increased epithelial marker E-cadherin expression and triggered a cobblestone-like morphology of MCF-7 cells, while reciprocally decreasing the expression of mesenchymal markers, such as snail, slug, and vimentin. In parallel with EMT reversal, MR-3 downregulated the invasion and migration of MCF-7 cells. Exploring the action mechanism of MR-3 on the suppression of EMT and invasion indicates that MR-3 markedly reduced the expression and nuclear translocation of β-catenin, accompanied with the downregulation of β-catenin target genes and the increment of membrane-bound β-catenin. These results suggest the involvement of Wnt/β-catenin signaling in the MR-3-induced EMT reversion of MCF-7 cells. Notably, MR-3 restored glycogen synthase kinase-3β activity by inhibiting the phosphorylation of Akt, the event required for β-catenin destruction via a proteasome-mediated system. Overall, these findings indicate that the anti-invasive activity of MR-3 on MCF-7 cells may result from the suppression of EMT via down-regulating phosphatidylinositol 3-kinase (PI3K)/AKT signaling, and consequently, β-catenin nuclear translocation. These occurrences ultimately lead to the blockage of EMT and the invasion of breast cancer cells. - Highlights: • MR-3 blocked MCF-7 cell invasion by inducing a reversal of EMT. • Wnt/β-catenin signaling is involved in MR-3-induced EMT

  7. 3,5,4′-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/β-catenin signaling cascades and reversal of epithelial–mesenchymal transition

    International Nuclear Information System (INIS)

    The molecular basis of epithelial–mesenchymal transition (EMT) functions as a potential therapeutic target for breast cancer because EMT may endow breast tumor-initiating cells with stem-like characteristics and enable the dissemination of breast cancer cells. We have recently verified the antitumor activity of 3,5,4′-trimethoxystilbene (MR-3), a naturally methoxylated derivative of resveratrol, in colorectal cancer xenografts via an induction of apoptosis. The effect of MR-3 on EMT and the invasiveness of human MCF-7 breast adenocarcinoma cell line were also explored. We found that MR-3 significantly increased epithelial marker E-cadherin expression and triggered a cobblestone-like morphology of MCF-7 cells, while reciprocally decreasing the expression of mesenchymal markers, such as snail, slug, and vimentin. In parallel with EMT reversal, MR-3 downregulated the invasion and migration of MCF-7 cells. Exploring the action mechanism of MR-3 on the suppression of EMT and invasion indicates that MR-3 markedly reduced the expression and nuclear translocation of β-catenin, accompanied with the downregulation of β-catenin target genes and the increment of membrane-bound β-catenin. These results suggest the involvement of Wnt/β-catenin signaling in the MR-3-induced EMT reversion of MCF-7 cells. Notably, MR-3 restored glycogen synthase kinase-3β activity by inhibiting the phosphorylation of Akt, the event required for β-catenin destruction via a proteasome-mediated system. Overall, these findings indicate that the anti-invasive activity of MR-3 on MCF-7 cells may result from the suppression of EMT via down-regulating phosphatidylinositol 3-kinase (PI3K)/AKT signaling, and consequently, β-catenin nuclear translocation. These occurrences ultimately lead to the blockage of EMT and the invasion of breast cancer cells. - Highlights: • MR-3 blocked MCF-7 cell invasion by inducing a reversal of EMT. • Wnt/β-catenin signaling is involved in MR-3-induced EMT

  8. Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

    International Nuclear Information System (INIS)

    Purpose: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. Methods and Materials: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status. Results: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). Conclusion: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.

  9. Breast Cancer in India: Etiology, Diagnosis and Therapy

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Peepliwal

    2013-06-01

    Full Text Available Breast cancer accounts for more than 20% Indian women in India. The mortality is still higher than the cervix cancer even though the descriptive etiology, early diagnosis tools and best therapies are available for the breast cancer. As for as Indian women concerns, most of them are not aware about the myths and facts of hidden anatomy of breast, cause, diagnosis followed by the treatment required to cure the evil disease i.e. breast cancer. This review mainly focuses on etiology of breast cancer, types of breast cancers i.e. Ductal carcinoma in situ (DCIS, Invasive ductal carcinoma, Lobular carcinoma in situ (LCIC, Invasive lobular carcinoma, Inflammatory breast disease, various diagnostic tools used to characterize the type of diseases, various methods to detect the stages of cancers, advanced imaging techniques (Ultrasound, MRI,CT Scan, PET Scan etc. and other biopsy tests required to assess the breast cancer followed by the better treatment to improve the morbidity. The extensive literature review done on this topic and this literature review would be helpful to the community updating about the breast cancer, how one can diagnose the evil disease on time and get the best therapy available to live life happily.

  10. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P;

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  11. Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection

    Science.gov (United States)

    Lambros, Maryou B; Campion-Flora, Adriana; Rodrigues, Daniel Nava; Gauthier, Arnaud; Cabral, Cecilia; Pawar, Vidya; Mackay, Alan; A’Hern, Roger; Marchiò, Caterina; Palacios, Jose; Natrajan, Rachael; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCIS and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDCs were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridisation (aCGH), and Sequenom MassARRAY (Oncocarta v1.0 panel). Fluorescence in situ hybridisation and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCIS and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (i.e. 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case, the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations. PMID:22252965

  12. The Most Common New Cases of Breast Cancer among the Housewives: The Some Carcinogenic Determinants

    Directory of Open Access Journals (Sweden)

    Nurka Pranjić

    2014-06-01

    CONCLUSION: The most common new cases of breast cancer were among housewife. Inverse significantly link between breast cancer and poverty, arrival time of menopause and distant-cousin- degree family history were found. For most women, physical activity may reduce the risk of invasive breast cancer.

  13. Advances in the surgical treatment of breast cancer.

    Science.gov (United States)

    Xing, Lei; He, Qiang; Wang, Yuan-Yuan; Li, Hong-Yuan; Ren, Guo-Sheng

    2016-06-01

    Breast cancer has become the top malignant neoplasm in Chinese women with an increasing risk of morbidity and mortality. As a crucial part of comprehensive treatment of breast cancer, breast surgical technique is ceaselessly ameliorating and enriching its features. With the purpose of achieving minimal surgical intervention and satisfactory cosmetic results, the trend of mammary surgery is focusing on minimally invasive treatment and aesthetics in the 21st century. This article gives an overview of the most representative surgical procedures, such as breast conservative surgery, sentinel lymph node dissection, oncoplastic technique and breast reconstructive surgery. PMID:27265302

  14. Abortion, Miscarriage, and Breast Cancer Risk

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk A woman’s hormone ... be conducted to determine whether having an induced abortion, or a miscarriage (also known as spontaneous abortion), ...

  15. Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

    International Nuclear Information System (INIS)

    One of the major goals in cancer research is to find and evaluate the early presence of biomarkers in human fluids and tissues. To resolve the complex cell heterogeneity of a tumor mass, it will be useful to characterize the intricate biomolecular composition of tumor microenvironment (the so called cancer secretome), validating secreted proteins as early biomarkers of cancer initiation and progression. This approach is not broadly applicable because of the paucity of well validated and FDA-approved biomarkers and because most of the candidate biomarkers are mainly organ-specific rather than tumor-specific. For these reasons, there is an urgent need to identify and validate a panel of biomarker combinations for early detection of human tumors. This is especially important for breast cancer, the cancer spread most worldwide among women. It is well known that patients with early diagnosed breast cancer live longer, require less extensive treatment and fare better than patients with more aggressive and/or advanced disease. In the frame of searching breast cancer biomarkers (especially using nipple aspirate fluid mirroring breast microenvironment), studies have highlighted an optimal combination of well-known biomarkers: uPA + PAI-1 + TF. When individually investigated they did not show perfect accuracy in predicting the presence of breast cancer, whereas the triple combination has been demonstrated to be highly predictive of pre-cancer and/or cancerous conditions, approaching 97-100% accuracy. Despite the heterogeneous composition of breast cancer and the difficulties to find specific breast cancer biomolecules, the noninvasive analysis of the nipple aspirate fluid secretome may significantly improve the discovery of promising biomarkers, helping also the differentiation among benign and invasive breast diseases, opening new frontiers in early oncoproteomics

  16. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

    Breast cancer is the most common type of cancer in women. Imaging techniques play a pivotal role in breast cancer management, especially in lesion detection, treatment planning and evaluation, and prognostication. These imaging techniques have however limitations such as the use of ionizing radiatio

  17. Risk Factors for Premenopausal Breast Cancer in Bangladesh

    Directory of Open Access Journals (Sweden)

    Javaid Iqbal

    2015-01-01

    Full Text Available Background. The incidence of premenopausal breast cancer is rising throughout South Asia. Our objective was to determine the role of risk factors associated with Westernization for premenopausal breast cancer in Bangladesh. Methods. We conducted a matched case-control study between January 1, 2007, and December 31, 2010, at four hospitals in Bangladesh. Cases were premenopausal women diagnosed with invasive breast cancer. Controls were premenopausal women with no personal history of breast cancer. Logistic regression was used to calculate the odds ratios (OR for breast cancer. Results. We identified 129 age-matched pairs. The mean age of breast cancer diagnosis was 37.5 years. Each year decrease in the age of menarche significantly increased the risk of breast cancer (OR = 1.67, 95% CI 1.09–2.56, P=0.02. The risk was also increased with a current body mass index of ≥25 kg/m2 (OR = 5.24, 95% CI 1.10–24.9, P=0.04. Age at first childbirth, parity, and breastfeeding were not significantly associated with premenopausal breast cancer risk (P>0.05. Conclusions. Age at menarche and adult weight gain were associated with premenopausal breast cancer risk. Other factors associated with Westernization may not be relevant to premenopausal breast cancer risk in Bangladesh.

  18. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

    OpenAIRE

    Vestey, Sarah B; Perks, Claire M.; Sen, Chandan; Calder, Caroline J; Holly, Jeff MP; Winters, Zoe E

    2004-01-01

    Introduction Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In v...

  19. FAK activation is required for IGF1R-mediated regulation of EMT, migration, and invasion in mesenchymal triple negative breast cancer cells

    OpenAIRE

    Taliaferro-Smith, LaTonia; Oberlick, Elaine; Liu, Tongrui; McGlothen, Tanisha; Alcaide, Tiffanie; Tobin, Rachel; Donnelly, Siobhan; Commander, Rachel; Kline, Erik; Nagaraju, Ganji Purnachandra; Havel, Lauren; Marcus, Adam; Nahta, Rita; O'Regan, Ruth

    2015-01-01

    Triple negative breast cancer (TNBC) is a highly metastatic disease that currently lacks effective prevention and treatment strategies. The insulin-like growth factor 1 receptor (IGF1R) and focal adhesion kinase (FAK) signaling pathways function in numerous developmental processes, and alterations in both are linked with a number of common pathological diseases. Overexpression of IGF1R and FAK are closely associated with metastatic breast tumors. The present study investigated the interrelati...

  20. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    OpenAIRE

    Arwa Flemban; David Qualtrough

    2015-01-01

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in t...

  1. Exemestane Reduces Breast Cancer Risk in High-Risk Postmenopausal Women

    Science.gov (United States)

    Clinical trial results presented at the 2011 ASCO annual meeting showed that the aromatase inhibitor exemestane—used to treat early and advanced breast cancer—substantially reduced the risk of invasive breast cancer in high-risk postmenopausal women.

  2. Tamoxifen Resistance in Breast Cancer

    OpenAIRE

    Chang, Minsun

    2012-01-01

    Tamoxifen is a central component of the treatment of estrogen receptor (ER)-positive breast cancer as a partial agonist of ER. It has been clinically used for the last 30 years and is currently available as a chemopreventive agent in women with high risk for breast cancer. The most challenging issue with tamoxifen use is the development of resistance in an initially responsive breast tumor. This review summarizes the roles of ER as the therapeutic target of tamoxifen in cancer treatment, clin...

  3. Green Tea and Breast Cancer

    OpenAIRE

    Wu, Anna H.; Butler, Lesley M.

    2011-01-01

    The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort stud...

  4. Estrogens and breast cancer

    Directory of Open Access Journals (Sweden)

    HANKINSON SUSAN E

    1997-01-01

    Full Text Available In this review, we summarize the epidemiologic evidence for the associations of oral contraceptives and postmenopausal hormones with risk of breast cancer. We also describe the biologic plausibility of these relationships. Overall, there appears to be little, if any, increase in risk with oral contraceptive use in general, even among users for 10 or more years. However, compared to never users, current oral contraceptive users appear to have a modest elevation in risk that subsides within about 10 years after cessation of use. For postmenopausal hormones, the weight of the evidence suggests little or no increase in risk among users of short duration, or for use in the past. However, current longer term use is associated with an increased risk of breast cancer that increases with duration. This increase in risk is large enough, and well enough supported, to be considered along with the other risks and benefits of postmenopausal hormone therapy.

  5. The Basic Facts of Korean Breast Cancer in 2013: Results of a Nationwide Survey and Breast Cancer Registry Database.

    Science.gov (United States)

    Min, Sun Young; Kim, Zisun; Hur, Min Hee; Yoon, Chan Seok; Park, Eun-Hwa; Jung, Kyu-Won

    2016-03-01

    The Korean Breast Cancer Society (KBCS) has reported a nationwide breast cancer data since 1996. We present a comprehensive report on the facts and trends of breast cancer in Korea in 2013. Data on the newly diagnosed patients in the year 2013 were collected from 99 hospitals by using nationwide questionnaire survey. Clinical characteristics such as stage of cancer, histologic types, biological markers, and surgical management were obtained from the online registry database. A total of 19,316 patients were newly diagnosed with breast cancer in 2013. The crude incidence rate of female breast cancer including carcinoma in situ was 76.2 cases per 100,000 women. The median age at diagnosis was 50 years, and the proportions of postmenopausal women with breast cancer accounted for more than half of total patients. The proportion of early breast cancer increased consistently, and the pathologic features have changed accordingly. Breast-conserving surgery was performed in more cases than total mastectomy in the year. The total number of breast reconstruction surgeries markedly increased approaching 3-fold in last 11 years. According to annual percentile change of invasive cancer incidence, the incidence increased rapidly until 2010. And thereafter the increase of it became steadier. For ductal carcinoma in situ, the incidence consistently increased during the same period without any joinpoint. Analysis of nationwide registry data will contribute to defining of the trends and characteristics of breast cancer in Korea.

  6. Proteomic classification of breast cancer.

    LENUS (Irish Health Repository)

    Kamel, Dalia

    2012-11-01

    Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

  7. A systematic review of bevacizumab efficacy in breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Christiansen, Ole Grummedal; Nielsen, Dorte Lisbet

    2014-01-01

    UNLABELLED: Angiogenesis is a key component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for the treatment of cancer. We systematically describe phase II and III clinical trials of bevacizumab for the treatment of breast cancer. METHODS...

  8. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

    International Nuclear Information System (INIS)

    Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians

  9. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3

    Directory of Open Access Journals (Sweden)

    Lund Eiliv

    2009-07-01

    Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.

  10. Cathepsin b: a potential prognostic marker for inflammatory breast cancer

    OpenAIRE

    Cavallo-Medved Dora; Shaalan Mohamed A; El-Shinawi Mohamed; Mohamed Mona M; Nouh Mohamed A; Khaled Hussein M; Sloane Bonnie F

    2011-01-01

    Abstract Background Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC. Methods In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IB...

  11. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... for Lung Cancer June 15, 2009 Welcome to this “OR-Live” webcast presentation, premiering from Beth Israel ... number one cause of cancer-related deaths in this country. It far exceeds breast cancer, colon cancer, ...

  12. Breast Cancer Chemoprevention: Old and New Approaches

    Directory of Open Access Journals (Sweden)

    Massimiliano Cazzaniga

    2012-01-01

    Full Text Available In 1976, Sporn has defined chemoprevention as “the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred.” Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings in selected high-risk populations suggests that chemoprevention is a rational and an appealing strategy. Breast cancer chemoprevention has focused heavily on endocrine intervention using selective estrogen receptor modulators (SERMs and aromatase inhibitors (AIs. Achieving much success in this particular setting and new approaches as low-dose administration are actually under investigations in several topics. Unfortunately, these drugs are active in prevention of endocrine responsive lesions only and have no effect in reducing the risk of estrogen-negative breast cancer. Thus, recently new pathways, biomarkers, and agents likely are to be effective in this subgroup of cancers and were put under investigation. Moreover, the identification of new potential molecular targets and the development of agents aimed at these targets within cancer have already had a significant impact on advanced cancer therapy and provide a wealth of opportunities for chemoprevention. This paper will highlight current clinical research in both ER-positive and ER-negative breast cancer chemoprevention, explaining the biologic effect of the various agents on carcinogenesis and precancerous lesions, and finally presenting an excursus on the state-of-the-art about new molecular targets under investigations in breast cancer settings.

  13. Melatonin: an inhibitor of breast cancer.

    Science.gov (United States)

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

    2015-06-01

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

  14. Radiofrequency Heat-Enhanced Chemotherapy for Breast Cancer: Towards Interventional Molecular Image-Guided Chemotherapy

    OpenAIRE

    Zhou, Yurong; Han, Guocan; Wang, Yue; Hu, Xi; Li, Zhiming; Chen, Lumin; Bai, Weixian; Luo, Jingfeng; Zhang, Yajing; Sun, Jihong; Yang, Xiaoming

    2014-01-01

    Breast cancer is the most common malignancy in women worldwide. Recent developments in minimally invasive interventional radiology techniques have significantly improved breast cancer treatment. This study aimed to develop a novel technique for the local management of breast cancers using radiofrequency heat (RFH). We performed both in vitro experiments using human breast cancer cells and in vivo validation in xenograft animal models with magnetic resonance imaging (MRI) and pathological corr...

  15. EFFECTS OF ESTETROL ON MIGRATION AND INVASION IN T47-D BREAST CANCER CELLS THROUGH THE ACTIN CYTOSKELETON