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Sample records for breast cancer invasion

  1. [Lobular neoplasms and invasive lobular breast cancer].

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    Sinn, H-P; Helmchen, B; Heil, J; Aulmann, S

    2014-02-01

    The term lobular neoplasia (LN) comprises both atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) and thus a spectrum of morphologically heterogeneous but clinically and biologically related lesions. LN is regarded as a nonobligatory precursor lesion of invasive breast cancer and at the same time as an indicator lesion for ipsilateral and contralateral breast cancer risk of the patient. Rare pleomorphic or florid variants of LCIS must be differentiated from classical LCIS. The classical type of invasive lobular carcinoma (ILC) can be distinguished from the non-special type of invasive breast cancer (NST) by E-cadherin inactivation, loss of E-cadherin related cell adhesion and the subsequent discohesive growth pattern. Variant forms of ILC may show different molecular features, and solid and pleomorphic differentiation patterns in cases of high grade variants. Important parameters for the prognostic assessment of ILC are tumor grading and the recognition of morphological variants.

  2. Epigenetic suppression of neprilysin regulates breast cancer invasion

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    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

  3. Pathologic findings in nonpalpable invasive breast cancer.

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    McKinney, C D; Frierson, H F; Fechner, R E; Wilhelm, M C; Edge, S B

    1992-01-01

    Previous studies have shown that patients with nonpalpable invasive breast cancer have a favorable prognosis. These studies, however, have not analyzed pathologic features of mammographically detected tumors according to tumor size. We describe the histopathologic features of 77 nonpalpable invasive breast cancers, comparing neoplasms less than or equal to 1 cm with larger clinically occult tumors. Forty-seven lesions (61%) were less than or equal to 1 cm (group A) and 30 (39%) were greater than 1 cm (group B). In group A, there were 30 infiltrating ductal carcinomas (IDC); seven infiltrating lobular carcinomas (ILC); and two cases each of mixed ILC and IDC, mixed tubular carcinoma and ILC, and infiltrating cribriform carcinoma. There was one case each of mucinous carcinoma, apocrine carcinoma, tubular carcinoma, and mixed mucinous and IDC. In group B, there were 23 (77%) IDC, five (17%) ILC, and two mixed IDC and ILC. Tumors in group B were more frequently grade 3 (22% versus 7%), but this was not statistically significant (p = 0.21). There were no important differences in the frequency, subtypes and location of carcinoma in situ, or other histopathologic parameters evaluated in the biopsy specimens. Mastectomy specimens with axillary lymph node dissections were available for review in 64 cases (83%). Group B patients had a higher rate of residual invasive carcinoma (31% versus 13%) and lymph node metastases (31% versus 16%), but these differences were not statistically significant. Residual carcinoma in situ was more frequent in group B (54%) compared with group A (26%) (p = .036). Of seven group B cases with negative biopsy margins, residual invasive carcinoma was present in five (71%). We conclude that small nonpalpable invasive breast cancers differ from larger nonpalpable tumors primarily in size. The finding of negative biopsy margins should not be construed as conclusive evidence for the absence of residual infiltrating disease.

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

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    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.

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

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    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. Perspectives of Nanotechnology in Minimally Invasive Therapy of Breast Cancer

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    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.

  7. Invasive ductal breast cancer metastatic to the sigmoid colon

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    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.

  8. Precursor lesions of invasive breast cancer

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    Schreer, Ingrid [Breast Center, University Hospital Kiel, Kiel (Germany)]. E-mail: ischreer@email.uni-kiel.de; Luettges, Jutta [Department of Pathology, University Hospital Kiel, Kiel (Germany)

    2005-04-01

    The increasing application of mammography, mainly in screening programs for the early detection of breast cancer, and the high technical standard of imaging has resulted in the detection of clinically occult breast tumors. Considering that only diagnosis at an early stage will be able to change the prognosis of breast cancer, this diagnostic challenge appears to be the most exciting field in both breast imaging and breast pathology. Especially the precursor lesions need to be diagnosed and defined precisely to understand their prognostic significance. In imaging, the morphologic appearance of precursor lesions is usually neither typical nor pathognomonic. They have to be assessed histologically using percutaneous interventions. Recent molecular studies have demonstrated various genetic alterations in the ductal epithelium, with the earliest onset in atypical ductal hyperplasia. The recent WHO classification, which is based on molecular data and histopathological features, attempts to define in particular the precursor lesions and low grade intraductal carcinomas. The clinical importance of the various grades has to be assessed. Intimate cooperation between diagnostic radiologist and pathologist is essential.

  9. Precursor lesions of invasive breast cancer.

    Science.gov (United States)

    Schreer, Ingrid; Lüttges, Jutta

    2005-04-01

    The increasing application of mammography, mainly in screening programs for the early detection of breast cancer, and the high technical standard of imaging has resulted in the detection of clinically occult breast tumors. Considering that only diagnosis at an early stage will be able to change the prognosis of breast cancer, this diagnostic challenge appears to be the most exciting field in both breast imaging and breast pathology. Especially the precursor lesions need to be diagnosed and defined precisely to understand their prognostic significance. In imaging, the morphologic appearance of precursor lesions is usually neither typical nor pathognomonic. They have to be assessed histologically using percutaneous interventions. Recent molecular studies have demonstrated various genetic alterations in the ductal epithelium, with the earliest onset in atypical ductal hyperplasia. The recent WHO classification, which is based on molecular data and histopathological features, attempts to define in particular the precursor lesions and low grade intraductal carcinomas. The clinical importance of the various grades has to be assessed. Intimate cooperation between diagnostic radiologist and pathologist is essential.

  10. HIPK2 downregulates vimentin and inhibits breast cancer cell invasion.

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    Nodale, Cristina; Sheffer, Michal; Jacob-Hirsch, Jasmine; Folgiero, Valentina; Falcioni, Rita; Aiello, Aurora; Garufi, Alessia; Rechavi, Gideon; Givol, David; D'Orazi, Gabriella

    2012-02-15

    Vimentin, a mesenchymal marker, is frequently overexpressed in epithelial carcinomas undergoing epithelial to mesenchymal transition (EMT), a condition correlated with invasiveness and poor prognosis. Therefore, vimentin is a potential molecular target for anticancer therapy. Emerging studies in experimental models underscore the functions of homeodomain-interacting protein kinase 2 (HIPK2) as potential oncosuppressor by acting as transcriptional corepressor or catalytic activator of molecules involved in apoptosis and response to antitumor drugs. However, an involvement of HIPK2 in limiting tumor invasion remains to be elucidated. This study, by starting with a microarray analysis, demonstrates that HIPK2 downregulates vimentin expression in invasive, vimentin-positive, MDA-MB-231 breast cancer cells and in the non-invasive MCF7 breast cancer cells subjected to chemical hypoxia, a drive for mesenchymal shift and tumor invasion. At functional level, vimentin downregulation by HIPK2 correlates with inhibition of breast tumor cell invasion. Together, these data show that vimentin is a novel target for HIPK2 repressor function and that HIPK2-mediated vimentin downregulation can contribute to inhibition of breast cancer cells invasion that might be applied in clinical therapy.

  11. Overweight, Obesity and Postmenopausal Invasive Breast Cancer Risk

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    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

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

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    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.

  13. Host epithelial geometry regulates breast cancer cell invasiveness

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    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. Accessory Breast Cancer Occurring Concurrently with Bilateral Primary Invasive Breast Carcinomas: A Report of Two Cases and Literature Review

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    Hao, Jin-yan; Yang, Cui-cui; Liu, Fang-Fang; Yang, Yi-Ling; Li, Shuai; Li, Wei-Dong; LI, YA-QING; Lang, Rong-gang; Fan, Yu; Paulos, Estifanos; Zhang, Xin-Min; Fu, Li

    2012-01-01

    The development of accessory breast tissue, which is found anywhere along the milk line, is attributed to the failure of milk line remnants to regress during embryogenesis. Primary tumors may arise from any ectopic breast tissue. Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare. Two such cases were reported in this article. One was a 43-year-old Chinese female who exhibited bilateral breast cancer (invasive ductal carcinoma, not otherwise sp...

  15. Role of Seprase in Breast Cancer Invasion

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    1998-09-01

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  16. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

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

    2015-10-08

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

  17. Contrast-enhanced dedicated breast CT detection of invasive breast cancer preceding mammographic diagnosis

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    Nicolas D. Prionas, MD, PhD

    2015-01-01

    Full Text Available Dedicated breast computed tomography (bCT generates high-resolution, three-dimensional images of the pendent uncompressed breast. Intravenous iodinated contrast during bCT provides additional physiologic information. In this case, a 10.0-mm invasive ductal carcinoma was visualized using contrast-enhanced breast CT one year before mammographic detection. Mammography four months before bCT was negative. The bCT contrast enhancement pattern closely matched the dynamic contrast-enhanced MRI obtained after diagnosis. Lesion enhancement at contrast-enhanced breast CT matched previously published enhancement values of breast cancer. Contrast-enhanced dedicated bCT provided high-resolution tomographic images and physiologic contrast enhancement data that facilitated the detection of an early breast cancer.

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

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    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

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

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    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...

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

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    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.

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

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    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.

  2. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells

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    Lin Ling

    2011-09-01

    Full Text Available Abstract Background Tumor-associated macrophages (TAMs are alternatively activated cells induced by interleukin-4 (IL-4-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells. Results We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway. Conclusions We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Lifetime recreational and occupational physical activity and risk of in situ and invasive breast cancer.

    Science.gov (United States)

    Sprague, Brian L; Trentham-Dietz, Amy; Newcomb, Polly A; Titus-Ernstoff, Linda; Hampton, John M; Egan, Kathleen M

    2007-02-01

    Numerous studies have observed reduced breast cancer risk with increasing levels of physical activity, yet these findings have been inconsistent about optimal times of activity and effect modification by other factors. We investigated the association between recreational and occupational physical activity and breast cancer risk in a population-based case-control study in Massachusetts, New Hampshire, and Wisconsin. During structured telephone interviews, 7,630 controls, 1,689 in situ, and 6,391 invasive breast cancer cases, ages 20 to 69 years, reported lifetime history of recreational physical activity and occupation. Neither lifetime recreational nor strenuous occupational physical activity appeared to be associated with risk of breast carcinoma in situ. In contrast, recreational physical activity was associated with a reduced risk of invasive breast cancer. After adjustment for potentially confounding factors, women averaging >6 h per week of strenuous recreational activity over their lifetime had a 23% reduction in the odds ratio of invasive breast cancer when compared with women reporting no recreational activity (95% confidence interval, 0.65-0.92; P(trend) = 0.05). However, this reduction in risk was limited to women without a first-degree family history of breast cancer (P(interaction) = 0.02). Inverse associations were observed for physical activity early in life, in the postmenopausal years, and in the recent past, but these findings were confined to women without a family history of breast cancer. Lifetime strenuous occupational activity was not associated with invasive breast cancer risk. These results provide further evidence that, for most women, physical activity may reduce the risk of invasive breast cancer.

  9. 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.

  10. Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis.

    Science.gov (United States)

    Arjonen, Antti; Kaukonen, Riina; Mattila, Elina; Rouhi, Pegah; Högnäs, Gunilla; Sihto, Harri; Miller, Bryan W; Morton, Jennifer P; Bucher, Elmar; Taimen, Pekka; Virtakoivu, Reetta; Cao, Yihai; Sansom, Owen J; Joensuu, Heikki; Ivaska, Johanna

    2014-03-01

    Mutations of the tumor suppressor TP53 are present in many forms of human cancer and are associated with increased tumor cell invasion and metastasis. Several mechanisms have been identified for promoting dissemination of cancer cells with TP53 mutations, including increased targeting of integrins to the plasma membrane. Here, we demonstrate a role for the filopodia-inducing motor protein Myosin-X (Myo10) in mutant p53-driven cancer invasion. Analysis of gene expression profiles from 2 breast cancer data sets revealed that MYO10 was highly expressed in aggressive cancer subtypes. Myo10 was required for breast cancer cell invasion and dissemination in multiple cancer cell lines and murine models of cancer metastasis. Evaluation of a Myo10 mutant without the integrin-binding domain revealed that the ability of Myo10 to transport β₁ integrins to the filopodia tip is required for invasion. Introduction of mutant p53 promoted Myo10 expression in cancer cells and pancreatic ductal adenocarcinoma in mice, whereas suppression of endogenous mutant p53 attenuated Myo10 levels and cell invasion. In clinical breast carcinomas, Myo10 was predominantly expressed at the invasive edges and correlated with the presence of TP53 mutations and poor prognosis. These data indicate that Myo10 upregulation in mutant p53-driven cancers is necessary for invasion and that plasma-membrane protrusions, such as filopodia, may serve as specialized metastatic engines.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Risk of subsequent invasive breast cancer after a diagnosis of ductal carcinoma in situ (DCIS).

    Science.gov (United States)

    Cheung, Shan; Booth, Mary E; Kearins, Olive; Dodwell, David

    2014-12-01

    Despite surgical removal of ductal carcinoma in situ (DCIS), recurrences still occur. This retrospective cohort study evaluated the risk of invasive recurrence following surgery and investigated factors which may be predictive of recurrence. We specifically investigated invasive recurrence with respect to mode of detection of DCIS. Patients whose DCIS was detected outside of the NHS Breast Screening Programme have a higher risk of subsequent ipsilateral invasive breast cancer than those whose DCIS is detected through screening. There is no significant difference in risk of subsequent contralateral invasive recurrence according to mode of detection.

  17. 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

  18. The a3 isoform of subunit a of the vacuolar ATPase localizes to the plasma membrane of invasive breast tumor cells and is overexpressed in human breast cancer.

    Science.gov (United States)

    Cotter, Kristina; Liberman, Rachel; Sun-Wada, GeHong; Wada, Yoh; Sgroi, Dennis; Naber, Stephen; Brown, Dennis; Breton, Sylvie; Forgac, Michael

    2016-07-19

    The vacuolar (H+)-ATPases (V-ATPases) are a family of ATP-driven proton pumps that acidify intracellular compartments and transport protons across the plasma membrane. Previous work has demonstrated that plasma membrane V-ATPases are important for breast cancer invasion in vitro and that the V-ATPase subunit a isoform a3 is upregulated in and critical for MDA-MB231 and MCF10CA1a breast cancer cell invasion. It has been proposed that subunit a3 is present on the plasma membrane of invasive breast cancer cells and is overexpressed in human breast cancer. To test this, we used an a3-specific antibody to assess localization in breast cancer cells. Subunit a3 localizes to the leading edge of migrating breast cancer cells, but not the plasma membrane of normal breast epithelial cells. Furthermore, invasive breast cancer cells express a3 throughout all intracellular compartments tested, including endosomes, the Golgi, and lysosomes. Moreover, subunit a3 knockdown in MB231 breast cancer cells reduces in vitro migration. This reduction is not enhanced upon addition of a V-ATPase inhibitor, suggesting that a3-containing V-ATPases are critical for breast cancer migration. Finally, we have tested a3 expression in human breast cancer tissue and mRNA prepared from normal and cancerous breast tissue. a3 mRNA was upregulated 2.5-47 fold in all breast tumor cDNA samples tested relative to normal tissue, with expression generally correlated to cancer stage. Furthermore, a3 protein expression was increased in invasive breast cancer tissue relative to noninvasive cancer and normal breast tissue. These studies suggest that subunit a3 plays an important role in invasive human breast cancer.

  19. 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.

  20. Risk Factors of the Invasive Breast Cancer Locoregional Recurrence

    Directory of Open Access Journals (Sweden)

    R. V. Liubota

    2015-01-01

    Full Text Available Background. The aim of the research was to estimate the frequency of the locoregional breast cancer recurrence appearance, the recurrence-free period continuance, and the 3- and 5-year survival depending on the scope of the surgical intervention, menstrual profile, and histological and molecular-biologic characteristics of the primary tumor. Patients and Methods. Among 218 patients with a breast cancer, 99 patients had breast-conserving surgery (BCS and 119 underwent radical mastectomy (RME; all patients had regional lymphatic nodes dissection. The size and the primary tumor differentiation degree, metastasis presence in the regional lymph nodes, ER expression, PR, and Her/2neu were assessed as the prognostics factors. Results. It was defined that the locoregional recurrence appearance frequency in patients with BCS turned out to be 13%, and in patients after RME it turned out to be 9%; the recurrence-free period continuance was 53±8 months and 56±10 months, respectively. Conclusions. The locoregional cancer recurrence frequency is higher in women with the menstrual function being preserved at the moment of the primary tumor detection than in postmenopausal patients and also in patients having the hyperexpression of the Her/2neu. The ipsilateral cancer recurrence decreases the 3-year survival by 7,1% and the 5-year one by 20,3%, respectively.

  1. Toll Like Receptor-9 Mediated Invasion in Breast Cancer

    Science.gov (United States)

    2012-07-01

    breast cancers because we also recently demon- strated a similar, decreased survival associated with low tumor TLR9 expression in renal cell carcinomas...epithelium in Helicobacter pylori infection . Clin Exp Immunol 136(3):521–526 9. Ilvesaro JM, Merrell MA, Swain TM, Davidson J, Zayzafoon M, Harris KW...KL, Sferruzzi-Perri AN, Thompson JG, Roberts CT (2010) Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy . Hum

  2. LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients.

    Science.gov (United States)

    Ahn, Sung Gwe; Dong, Seung Myung; Oshima, Akira; Kim, Woo Ho; Lee, Hak Min; Lee, Seung Ah; Kwon, Seung-Hyun; Lee, Ji-Hae; Lee, Jae Myun; Jeong, Joon; Lee, Hy-De; Green, Jeffrey E

    2013-08-01

    Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.

  3. 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.

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

    Science.gov (United States)

    Cekanova, Maria; Fernando, Romaine I; Siriwardhana, Nalin; Sukhthankar, Mugdha; De la Parra, Columba; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J; Wade, Paul A; Saxton, Arnold M; Donnell, Robert M; Pestell, Richard G; Dharmawardhane, Suranganie; Wimalasena, Jay

    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.

  5. Urinary Cadmium and Risk of Invasive Breast Cancer in the Women's Health Initiative.

    Science.gov (United States)

    Adams, Scott V; Shafer, Martin M; Bonner, Matthew R; LaCroix, Andrea Z; Manson, JoAnn E; Meliker, Jaymie R; Neuhouser, Marian L; Newcomb, Polly A

    2016-05-01

    Cadmium is a widespread heavy metal pollutant that may act as an exogenous estrogenic hormone. Environmental cadmium exposure has been associated with risk of breast cancer in retrospective studies. We prospectively assessed the relationship between cadmium exposure, evaluated by creatinine-normalized urinary cadmium concentration, and invasive breast cancer among 12,701 postmenopausal women aged ≥50 years in a Women's Health Initiative study of bone mineral density. After a median of 13.2 years of follow-up (1993-2010), 508 cases of invasive breast cancer and 1,050 comparison women were identified for a case-cohort analysis. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. Risk of breast cancer was not associated with urinary cadmium parameterized either in quartiles (comparing highest quartile with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval: 0.86, 1.03). We did not observe an association between urinary cadmium and breast cancer risk in any subgroup examined, including never smokers and women with body mass index (weight (kg)/height (m)(2)) less than 25. Results were consistent in both estrogen receptor-positive and estrogen receptor-negative tumors. Our results do not support the hypothesis that environmental cadmium exposure is associated with risk of postmenopausal breast cancer.

  6. 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.

  7. 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.

  8. Options in the local management of invasive breast cancer.

    Science.gov (United States)

    Nixon, A J; Troyan, S L; Harris, J R

    1996-08-01

    Newly diagnosed, early-stage breast cancer confronts the patient and her clinician with multiple treatment decisions. This review examines some of these local treatment options including the choice between breast-conserving treatment (BCT) and mastectomy, how best to treat the axilla, and the optimal sequencing of local and systemic therapy. Key elements in the selection of patients for BCT or mastectomy include preoperative mammography, careful pathological evaluation, and an assessment of patient desires in order to balance the risk of local recurrence against preservation of a cosmetically acceptable breast. Although some absolute contraindications to BCT exist, most patients are candidates for BCT. The role of axillary dissection is currently being redefined, and in the future, more limited procedures may be able to identify patients who can avoid axillary dissection. The relationship between timing of breast surgery with regard to the menstrual cycle and outcome is intriguing but not yet established. As well, the appropriate sequencing of chemotherapy and radiotherapy (RT) after conservative surgery (CS) is uncertain, although randomized trials are beginning to shed some light on this issue. Whether all patients treated with CS require treatment with RT is another question that is currently under investigation. This article addresses these issues, focusing on the specifics of treatment implementation.

  9. 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.

  10. 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.

  11. ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules.

    Science.gov (United States)

    Cui, Hong-Xia; Wang, Honglan; Wang, Yuchun; Song, Juan; Tian, Hua; Xia, Chunhui; Shen, Yetong

    2016-12-01

    Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated. In the present study, we aimed to investigate the influence of ST3Gal III on key steps in the process of breast cancer metastasis. ST3Gal III-overexpressing and ST3Gal III-silenced breast cancer MDA-MB-231 cell lines were generated. They showed an increase or decrease in the tumor-associated antigen sialyl-Lewis X (SLeX). The E-selectin binding capacity of the transfectants was proportional to cell surface SLeX levels. Cell migration and invasion were positively correlated with ST3Gal III levels. Moreover, ST3Gal III expression modulated the protein expression of invasion-related molecules, including β1 integrin, matrix metalloproteinase (MMP)-2, MMP-9 and cyclooxygenase-2, which may account for the mechanism involved in the effects of ST3Gal III on breast cancer invasiveness. In conclusion, our findings in these novel models of ST3Gal III expression revealed a critical requirement for ST3Gal III in several steps of breast cancer metastasis. ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules. This study provides novel insights into the mechanisms underlying metastasis and suggests a new target for the effective drug treatment of breast cancer metastasis.

  12. Gasdermin-B promotes invasion and metastasis in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Marta Hergueta-Redondo

    Full Text Available Gasdermin B (GSDMB belongs to the Gasdermin protein family that comprises four members (GSDMA-D. Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases. We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2 the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2. The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer.

  13. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke;

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessita......Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each...

  14. Reoperation Rates in Ductal Carcinoma In Situ vs Invasive Breast Cancer After Wire-Guided Breast-Conserving Surgery

    DEFF Research Database (Denmark)

    Langhans, Linnea; Jensen, Maj-Britt; Talman, Maj-Lis M;

    2017-01-01

    the Danish National Patient Registry that were cross-checked with the Danish Breast Cancer Group database and the Danish Pathology Register. Main Outcomes and Measures: Reoperation rate after wire-guided BCS in patients with IBC or DCIS. Results: Wire-guided BCS was performed in 4118 women (mean [SD] age, 60......Importance: New techniques for preoperative localization of nonpalpable breast lesions may decrease the reoperation rate in breast-conserving surgery (BCS) compared with rates after surgery with the standard wire-guided localization. However, a valid reoperation rate for this procedure needs...... to be established for comparison, as previous studies on this procedure include a variety of malignant and benign breast lesions. Objectives: To determine the reoperation rate after wire-guided BCS in patients with histologically verified nonpalpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS...

  15. Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC (p = 0.007, while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC (p = 0.006. Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023, ERα negativity (p = 0.001, and the HER2-driven and basal/triple-negative breast cancers (p = 0.018. Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001 and invasive breast cancer overexpressing EGFR (p = 0.019. We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120 (p<0.01. In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005. We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

  16. 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.

  17. Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0080 TITLE: Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. PRINCIPAL INVESTIGATOR...extracts. All samples have undergone a comprehensive DNA methylome analysis using the Illumina 450K CpG arrays, with excellent call rates, the

  18. UWB based low-cost and non-invasive practical breast cancer early detection

    Science.gov (United States)

    Vijayasarveswari, V.; Khatun, S.; Fakir, M. M.; Jusoh, M.; Ali, S.

    2017-03-01

    Breast cancer is one of the main causes of women death worldwide. Breast tumor is an early stage of cancer that locates in cells of a human breast. As there is no remedy, early detection is crucial. Towards this, Ultra-Wideband (UWB) is a prominent candidate. It is a wireless communication technology which can achieve high bandwidth with low power utilization. UWB is suitable to be used for short range communication systems including breast cancer detection since it is secure, non-invasive and human health friendly. This paper presents the low-cost and non-invasive early breast cancer detection strategy using UWB sensor (or antenna). Emphasis is given here to detect breast tumor in 2D and 3D environments. The developed system consisted of hardware and software. Hardware included UWB transceiver and a pair of home-made directional sensor/antenna. The software included feed-forward back propagation Neural Network (NN) module to detect the tumor existence, size and location along with soft interface between software and hardware. Forward scattering technique was used by placing two sensors diagonally opposite sides of a breast phantom. UWB pulses were transmitted from one side of phantom and received from other side, controlled by the software interface in PC environment. Collected received signals were then fed into the NN module for training, testing and validation. The system exhibited detection efficiency on tumor existence, location (x, y, z), and size were approximately 100%, (78.17%, 70.66%, 92.46%), 85.86% respectively. The proposed UWB based early breast cancer detection system could be more practical with low-cost, user friendly and non-harmful features. This project may help users to monitor their breast health regularly at their home.

  19. Potential of MR mammography to predict tumor grading of invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dietzel, M.; Baltzer, P.A.; Zoubi, R.; Groeschel, T.; Burmeister, H. [Jena Univ. (Germany). Inst. of Diagnostic and Interventional Radiology; Vag, T. [Technische Univ. Muenchen, Klinikum Rechts der Isar (Germany). Inst. fuer Roentgendiagnostik; Gajda, M. [Jena Univ. (Germany). Inst. of Pathology; Runnebaum, I.B. [Jena Univ. (Germany). Clinic of Gynecology; Kaiser, W.A. [Jena Univ. (Germany). Inst. of Diagnostic and Interventional Radiology; Harvard Univ., Boston, MA (United States). Medical School

    2011-09-15

    Purpose: Tumor grading (TG) is one of the most widely used prognostic factors in the case of breast cancer. This study aims to identify the potential of magnetic resonance mammography (MRM) to non-invasively assess TG. Materials and Methods: 399 invasive breast cancers were included (IRB approval; standardized clinical MRM protocols). All breast cancers were prospectively evaluated by two experienced (> 500 MRM) and blinded radiologists in consensus. In every cancer a set of 18 previously published MRM descriptors was assessed. These were assessed by univariate and multivariate analysis to identify the potential of MRM to predict TG (X2 statistics; binary logistic regression; area under the ROC curve [AUC]). Results: 8 of 18 MRM descriptors were associated with TG, e. g. internal structure, edema (p < 0.001), as well as skin thickening and destruction of the nipple line (p < 0.05). MRM was feasible to predict TG by multivariate analysis (p < 0.001). The highest potential could be identified to predict well differentiated breast cancers with good prognosis (AUC = 0.930). Conclusion: MR mammography was able to non-invasively assess tumor grading in a standard protocol. Since tumor grading is a surrogate for overall survival, these results provide further evidence to the clinical application of MR mammography as a noninvasive prognostic tool. (orig.)

  20. Dihydroavenanthramide D inhibits human breast cancer cell invasion through suppression of MMP-9 expression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young-Rae; Noh, Eun-Mi; Oh, Hyun Ju; Hur, Hyun; Kim, Jeong-Mi; Han, Ji-Hey; Hwang, Jin-Ki; Park, Byung-Hyun; Park, Jin-Woo [Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of); Youn, Hyun Jo; Jung, Sung Hoo [Department of Surgery, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of); Kim, Byeong-Soo; Jung, Ji-Youn; Lee, Sung-Ho [Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702 (Korea, Republic of); Park, Chang-Sik [Division of Animal Science and Resources Research Center for Transgenic Cloned Pigs, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Jong-Suk, E-mail: jsukim@jbnu.ac.kr [Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of)

    2011-02-25

    Research highlights: {yields} MMP-9 plays a pivotal role in the invasion of MCF-7 breast cancer cells. {yields} TPA stimulates MMP-9 expression through activation of MAPK/NF-{kappa}B and MAPK/AP-1 pathways. {yields} Dihydroavenanthramide D suppresses MMP-9 expression via inhibition of TPA-induced MAPK/NF-{kappa}B and MAPK/AP-1 activations. {yields} Dihydroavenanthramide D blocks cell invasion of MCF-7 breast cancer cells. -- Abstract: Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-{kappa}B), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-{kappa}B) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-{kappa}B and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.

  1. Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer.

    Science.gov (United States)

    Pang, Jia-Min B; Savas, Peter; Fellowes, Andrew P; Mir Arnau, Gisela; Kader, Tanjina; Vedururu, Ravikiran; Hewitt, Chelsee; Takano, Elena A; Byrne, David J; Choong, David Yh; Millar, Ewan Ka; Lee, C Soon; O'Toole, Sandra A; Lakhani, Sunil R; Cummings, Margaret C; Mann, G Bruce; Campbell, Ian G; Dobrovic, Alexander; Loi, Sherene; Gorringe, Kylie L; Fox, Stephen B

    2017-03-24

    The spectrum of genomic alterations in ductal carcinoma in situ (DCIS) is relatively unexplored, but is likely to provide useful insights into its biology, its progression to invasive carcinoma and the risk of recurrence. DCIS (n=20) with a range of phenotypes was assessed by massively parallel sequencing for mutations and copy number alterations and variants validated by Sanger sequencing. PIK3CA mutations were identified in 11/20 (55%), TP53 mutations in 6/20 (30%), and GATA3 mutations in 9/20 (45%). Screening an additional 91 cases for GATA3 mutations identified a final frequency of 27% (30/111), with a high proportion of missense variants (8/30). TP53 mutations were exclusive to high grade DCIS and more frequent in PR-negative tumors compared with PR-positive tumors (P=0.037). TP53 mutant tumors also had a significantly higher fraction of the genome altered by copy number than wild-type tumors (P=0.005), including a significant positive association with amplification or gain of ERBB2 (P<0.05). The association between TP53 mutation and ERBB2 amplification was confirmed in a wider DCIS cohort using p53 immunohistochemistry as a surrogate marker for TP53 mutations (P=0.03). RUNX1 mutations and MAP2K4 copy number loss were novel findings in DCIS. Frequent copy number alterations included gains on 1q, 8q, 17q, and 20q and losses on 8p, 11q, 16q, and 17p. Patterns of genomic alterations observed in DCIS were similar to those previously reported for invasive breast cancers, with all DCIS having at least one bona fide breast cancer driver event. However, an increase in GATA3 mutations and fewer copy number changes were noted in DCIS compared with invasive carcinomas. The role of such alterations as prognostic and predictive biomarkers in DCIS is an avenue for further investigation.Modern Pathology advance online publication, 24 March 2017; doi:10.1038/modpathol.2017.21.

  2. Female breast cancer in Świętokrzyskie Voivodeship in 1999–2012. New cases and the incidence of invasive breast cancer

    Directory of Open Access Journals (Sweden)

    Ewa Błaszkiewicz

    2015-07-01

    Full Text Available Introduction : Breast cancer is the most common malignant tumour among women in Poland. In 2012 invasive breast cancer was diagnosed in 17,000 Polish women. The effective fight against breast cancer is based on activities to prevent its occurrence or to enable early detection of the disease and then its effective treatment (cure. Aim of the research: To assess the prevalence of invasive breast cancer in women in Świętokrzyskie Voivodeship in 1999–2012. Material and methods: A total of 6079 new female invasive breast cancer cases were analysed. Crude rates (CRs and age-standarised rates (ASRs per 100,000 population were calculated. The total value of incidence rates was analysed for all ages (0–85+ and in separate age groups (15–49, 50–69, and 70–85+. Results : In 1999–2012 in Świętokrzyskie Voivodeship 6079 new invasive female breast cancer cases were diagnosed. Fifty-three percent of them were in the age group of 50–69 years, 25.0% in the age group 70–85+, and 21.5% in the age group 15–49 years. The incidence of BC in general (0–85+ increased from 41.2/105 in 1999 to 43.8/105 in 2012. In the women aged 15–49 years the value of ASRs of incidence increased. In the age group of 50–69 years the value of ASRs increased from 146.6/105 in 1999 to 163.5/105 in 2012. The increase in the incidence of breast cancer was reported among women in perimenopausal age and in premenopausal women. The decrease in breast cancer cases was observed among young, premenopausal women (15–49 years as well as among women over 70 years of age. Conclusions: Świętokrzyskie Voivodeship is a region in Poland with moderate risk of breast cancer.

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

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    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...

  5. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    Science.gov (United States)

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies.

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

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    Han, Miaojun [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Wang, Hailun [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Zhang, Hua-Tang [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Han, Zhaozhong, E-mail: zhaozhong.han@vanderbilt.edu [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Vanderbilt-Ingram Cancer Center, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. Black-Right-Pointing-Pointer Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. Black-Right-Pointing-Pointer 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.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    de Weger Roel A

    2009-06-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. VARIATION IN PRACTICE OF THE DIAGNOSTIC WORKUP OF ASYMPTOMATIC PATIENTS DIAGNOSED WITH INVASIVE BREAST CANCER

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    Anees eChagpar

    2016-03-01

    Full Text Available Introduction:Breast cancer is frequently diagnosed, yet variation remains in terms of practice patterns in presurgical workup. We sought to determine factors associated with this variation.Methods:An anonymous web-based survey was distributed to surgeons regarding their practices. Statistical analyses were conducted using SPSS.Results:253 surgeons responded to the survey. 17.0% were in academic practice, 37.5%% were hospital employed, and 41.5% were in private practice. 53.3% claimed that > 50% of their practice was breast-related. Surgeons were asked how often they would use various tests in the workup of an otherwise healthy asymptomatic patients, presenting with a non-palpable mammographic abnormality and a core needle biopsy showing invasive breast cancer. 23.5% stated they always would obtain a breast ultrasound, 17.2% stated they never would. 12.8% stated they never order a breast MRI; 4.1% always would. Workup of patients did not vary significantly based on number of years in practice nor practice setting. However, those whose practice was >50% breast were more likely to state that they would always order a breast ultrasound (32.5% vs. 12.9%, p<0.001, and less likely to state they would never order a breast MRI (3.4% vs. 25.8%, p<0.001. However, the proportions of surgeons who would always order a breast MRI was similar in the two groups (3.4% and 3.2%, respectively. Conclusions:These data highlight the lack of uniformity in the workup of asymptomatic patients presenting with non-palpable breast cancers, pointing to potential areas for improving value by minimizing variability.

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

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    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

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

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    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

  15. 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.

  16. 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.

  17. 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

  18. Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells

    Science.gov (United States)

    Wang, Yuan Yuan; Attané, Camille; Milhas, Delphine; Dirat, Béatrice; Dauvillier, Stéphanie; Guerard, Adrien; Gilhodes, Julia; Lazar, Ikrame; Alet, Nathalie; Laurent, Victor; Le Gonidec, Sophie; Hervé, Caroline; Bost, Frédéric; Ren, Guo Sheng; Bono, Françoise; Escourrou, Ghislaine; Prentki, Marc; Nieto, Laurence; Valet, Philippe

    2017-01-01

    In breast cancer, a key feature of peritumoral adipocytes is their loss of lipid content observed both in vitro and in human tumors. The free fatty acids (FFAs), released by adipocytes after lipolysis induced by tumor secretions, are transferred and stored in tumor cells as triglycerides in lipid droplets. In tumor cell lines, we demonstrate that FFAs can be released over time from lipid droplets through an adipose triglyceride lipase–dependent (ATGL-dependent) lipolytic pathway. In vivo, ATGL is expressed in human tumors where its expression correlates with tumor aggressiveness and is upregulated by contact with adipocytes. The released FFAs are then used for fatty acid β-oxidation (FAO), an active process in cancer but not normal breast epithelial cells, and regulated by coculture with adipocytes. However, in cocultivated cells, FAO is uncoupled from ATP production, leading to AMPK/acetyl-CoA carboxylase activation, a circle that maintains this state of metabolic remodeling. The increased invasive capacities of tumor cells induced by coculture are completely abrogated by inhibition of the coupled ATGL-dependent lipolysis/FAO pathways. These results show a complex metabolic symbiosis between tumor-surrounding adipocytes and cancer cells that stimulate their invasiveness, highlighting ATGL as a potential therapeutic target to impede breast cancer progression. PMID:28239646

  19. 2-Hydroxychalcone and xanthohumol inhibit invasion of triple negative breast cancer cells.

    Science.gov (United States)

    Kim, Sun Young; Lee, Ik-Soo; Moon, Aree

    2013-05-25

    Breast cancer is estimated as one of the most common causes of cancer death among women. In particular, triple negative breast cancers (TNBCs), which do not express the genes for estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2), have been associated with poor prognosis and metastasis. Chalcones, the biosynthetic precursors of flavonoids present in edible plants, exert cytotoxic and chemopreventive activities. Although mounting evidence suggests the anticancer properties of chalcones, limited information is available regarding the inhibitory effects of chalcones on the aggressiveness of breast cancer cells. The present study aimed to investigate the effects of chalcone and its derivatives on the growth and the invasiveness of TNBC cells. Here, we showed that treatment with chalcone, 2-hydroxychalcone, and xanthohumol for 24h inhibited the growth of MDA-MB-231 cells with IC50 values of 18.1, 4.6, and 6.7 μM, respectively. Similarly, Chalcone, 2-hydroxychalcone, and xanthohumol also exerted cytotoxicity in another TNBC cell line, Hs578T. Neohesperidin dihydrochalcone, 4-methoxychalcone, and hesperidin methylchalcone did not show the cytotoxicity on the MDA-MB-231 cells. Xanthohumol and 2-hydroxychalcone induced apoptosis by Bcl-2 downregulation. Importantly, 2-hydroxychalcone and xanthohumol exerted more potent inhibitory effects on the proliferation, MMP-9 expression and invasive phenotype of MDA-MB-231 than chalcone. These results suggest a potential application of these chalcones as anticancer agents that can alleviate malignant progression of TNBC.

  20. 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.

  1. Breast Cancer Migration and Invasion Depend on Proteasome Degradation of Regulator of G-Protein Signaling 4

    OpenAIRE

    Xie, Yan; Wolff, Dennis W.; Wei, Taotao; Wang, Bo; Deng, Caishu; Kirui, Joseph K.; Jiang, Haihong; Qin, Jianbing; Abel, Peter W.; Tu, Yaping

    2009-01-01

    Aberrant signaling through G-protein coupled receptors promotes metastasis, the major cause of breast cancer death. We identified regulator of G-protein signaling 4 (RGS4) as a novel suppressor of breast cancer migration and invasion, important steps of metastatic cascades. By blocking signals initiated through Gi-coupled receptors, such as protease-activated receptor 1 and CXC chemokine receptor 4, RGS4 disrupted Rac1-dependent lamellipodia formation, a key step involved in cancer migration ...

  2. Intracellular Expression of PAI-1 Specific Aptamers Alters Breast Cancer Cell Migration, Invasion and Angiogenesis.

    Science.gov (United States)

    Fortenberry, Yolanda M; Brandal, Stephanie M; Carpentier, Gilles; Hemani, Malvi; Pathak, Arvind P

    2016-01-01

    Plasminogen activator inhibitor-1 (PAI-1) is elevated in various cancers, where it has been shown to effect cell migration and invasion and angiogenesis. While, PAI-1 is a secreted protein, its intercellular levels are increased in cancer cells. Consequently, intracellular PAI-1 could contribute to cancer progression. While various small molecule inhibitors of PAI-1 are currently being investigated, none specifically target intracellular PAI-1. A class of inhibitors, termed aptamers, has been used effectively in several clinical applications. We previously generated RNA aptamers that target PAI-1 and demonstrated their ability to inhibit extracellular PAI-1. In the current study we explored the effect of these aptamers on intracellular PAI-1. We transiently transfected the PAI-1 specific aptamers into both MDA-MB-231 human breast cancer cells, and human umbilical vein endothelial cells (HUVECs) and studied their effects on cell migration, invasion and angiogenesis. Aptamer expressing MDA-MB-231 cells exhibited a decrease in cell migration and invasion. Additionally, intracellular PAI-1 and urokinase plasminogen activator (uPA) protein levels decreased, while the PAI-1/uPA complex increased. Moreover, a significant decrease in endothelial tube formation in HUVECs transfected with the aptamers was observed. In contrast, conditioned media from aptamer transfected MDA-MB-231 cells displayed a slight pro-angiogenic effect. Collectively, our study shows that expressing functional aptamers inside breast and endothelial cells is feasible and may exhibit therapeutic potential.

  3. Intracellular Expression of PAI-1 Specific Aptamers Alters Breast Cancer Cell Migration, Invasion and Angiogenesis

    Science.gov (United States)

    Fortenberry, Yolanda M.; Brandal, Stephanie M.; Carpentier, Gilles; Hemani, Malvi; Pathak, Arvind P.

    2016-01-01

    Plasminogen activator inhibitor-1 (PAI-1) is elevated in various cancers, where it has been shown to effect cell migration and invasion and angiogenesis. While, PAI-1 is a secreted protein, its intercellular levels are increased in cancer cells. Consequently, intracellular PAI-1 could contribute to cancer progression. While various small molecule inhibitors of PAI-1 are currently being investigated, none specifically target intracellular PAI-1. A class of inhibitors, termed aptamers, has been used effectively in several clinical applications. We previously generated RNA aptamers that target PAI-1 and demonstrated their ability to inhibit extracellular PAI-1. In the current study we explored the effect of these aptamers on intracellular PAI-1. We transiently transfected the PAI-1 specific aptamers into both MDA-MB-231 human breast cancer cells, and human umbilical vein endothelial cells (HUVECs) and studied their effects on cell migration, invasion and angiogenesis. Aptamer expressing MDA-MB-231 cells exhibited a decrease in cell migration and invasion. Additionally, intracellular PAI-1 and urokinase plasminogen activator (uPA) protein levels decreased, while the PAI-1/uPA complex increased. Moreover, a significant decrease in endothelial tube formation in HUVECs transfected with the aptamers was observed. In contrast, conditioned media from aptamer transfected MDA-MB-231 cells displayed a slight pro-angiogenic effect. Collectively, our study shows that expressing functional aptamers inside breast and endothelial cells is feasible and may exhibit therapeutic potential. PMID:27755560

  4. 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.

  5. G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis.

    Directory of Open Access Journals (Sweden)

    Matthew J Billard

    Full Text Available Triple negative breast cancer (TNBC is a heterogeneous disease that has a poor prognosis and limited treatment options. Chemokine receptor interactions are important modulators of breast cancer metastasis; however, it is now recognized that quantitative surface expression of one important chemokine receptor, CXCR4, may not directly correlate with metastasis and that its functional activity in breast cancer may better inform tumor pathogenicity. G protein coupled receptor kinase 3 (GRK3 is a negative regulator of CXCR4 activity, and we show that GRK expression correlates with tumorigenicity, molecular subtype, and metastatic potential in human tumor microarray analysis. Using established human breast cancer cell lines and an immunocompetent in vivo mouse model, we further demonstrate that alterations in GRK3 expression levels in tumor cells directly affect migration and invasion in vitro and the establishment of distant metastasis in vivo. The effects of GRK3 modulation appear to be specific to chemokine-mediated migration behaviors without influencing tumor cell proliferation or survival. These data demonstrate that GRK3 dysregulation may play an important part in TNBC metastasis.

  6. 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

  7. 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

  8. What Is Breast Cancer?

    Science.gov (United States)

    ... Research? Breast Cancer About Breast Cancer What Is Breast Cancer? Breast cancer starts when cells in the breast ... spread, see our section on Cancer Basics . Where breast cancer starts Breast cancers can start from different parts ...

  9. Tumor Phagocytes Promote Breast Cancer Invasion and Metastasis

    Science.gov (United States)

    2010-10-14

    passive physiological event to clear unwanted cells, we hypothesize that clearance of apoptotic tumor cells by tumor phagocytes produce soluble...FACS assay. Introduction: The purpose of cancer chemotherapy and immunotherapy is to kill cancer cells, mostly by apoptosis. Phagocytes, which...microenvironment for metastasis. A major barrier to effective anti-cancer immunotherapy is the ability of the host to mount a durable anti-tumor response [4

  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. 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.

  12. 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.

  13. Body mass index and survival after diagnosis of invasive breast cancer: a study based on the Japanese National Clinical Database-Breast Cancer Registry.

    Science.gov (United States)

    Kawai, Masaaki; Tomotaki, Ai; Miyata, Hiroaki; Iwamoto, Takayuki; Niikura, Naoki; Anan, Keisei; Hayashi, Naoki; Aogi, Kenjiro; Ishida, Takanori; Masuoka, Hideji; Iijima, Kotaro; Masuda, Shinobu; Tsugawa, Koichiro; Kinoshita, Takayuki; Nakamura, Seigo; Tokuda, Yutaka

    2016-06-01

    Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed-up for a median period of 6.7 years entered in the National Clinical Database-Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m(2) ) categories; cause, 937 breast cancer-specific deaths, and 2433 recurrences were observed. Obesity was associated with an increased risk of all-cause (HR: 1.46; 95% CI: 1.16-1.83) and breast cancer-specific death (HR: 1.47; 95% CI: 1.11-1.93) for all patients, and with all-cause (HR: 1.47; 95% CI: 1.13-1.92) and breast cancer-specific death (HR: 1.58; 95% CI: 1.13-2.20) for postmenopausal patients. Being underweight was associated with an increased risk of all-cause death for all (HR: 1.41; 95% CI: 1.16-1.71) and for postmenopausal patients (HR: 1.45; 95% CI: 1.15-1.84). With regard to subtype and menopausal status, obesity was associated with an increased risk of breast cancer-specific death for all cases of luminal B tumor (HR: 2.59; 95% CI: 1.51-4.43; Pheterogeneity of Luminal B vs. Triple negative = 0.016) and for postmenopausal patients with luminal B tumor (HR: 3.24; 95% CI: 1.71-6.17). Being obese or underweight is associated with a higher risk of death among female breast cancer patients in Japan.

  14. Multivitamin supplement use and risk of invasive breast cancer

    NARCIS (Netherlands)

    Meulepas, J.M.; Newcomb, P.A.; Burnett-Hartman, A.N.; Hampton, J.M.; Trentham-Dietz, A.

    2010-01-01

    Objective: Multivitamin supplements are used by nearly half of middle-aged women in the USA. Despite this high prevalence of multivitamin use, little is known about the effects of multivitamins on health outcomes, including cancer risk. Our main objective was to determine the association between mul

  15. miR-103 regulates triple negative breast cancer cells migration and invasion through targeting olfactomedin 4.

    Science.gov (United States)

    Xiong, Bin; Lei, Xuefeng; Zhang, Lei; Fu, Jia

    2017-03-18

    Our previous study showed olfactomedin 4 (OLFM4) suppressed triple-negative breast cancer cells migration, invasion and metastasis-associated protein MMP 9 expression. OLFM4 was identified as a potential target of miR-103 according to microRNA target databases and published studies. The aim of this study is to validate the relationship between miR-103 and OLFM4, and explore the function and clinical significance of miR-103 in triple-negative breast cancer patients. In our results, miR-103 negatively regulated OLFM4 expression by directly targeting its 3'-UTR. OLFM4 was a functional target of miR-103 to regulate triple-negative breast cancer cells migration, invasion and MMP 9 expression. Moreover, miR-103 overexpression was observed in triple-negative breast cancer tissues and cell lines, and associated with lymph node metastasis, distant metastasis and clinical stage. Univariate and multivariate analyses suggested that miR-103 overexpression was a poor independent prognostic factor for triple-negative breast cancer patients. In conclusion, miR-103 acts as an oncogene miRNA to promote triple-negative breast cancer cells migration and invasion through targeting OLFM4.

  16. KISS1R induces invasiveness of estrogen receptor-negative human mammary epithelial and breast cancer cells.

    Science.gov (United States)

    Cvetkovic, Donna; Dragan, Magdalena; Leith, Sean J; Mir, Zuhaib M; Leong, Hon S; Pampillo, Macarena; Lewis, John D; Babwah, Andy V; Bhattacharya, Moshmi

    2013-06-01

    Kisspeptins (KPs), peptide products of the KISS1 metastasis-suppressor gene, are endogenous ligands for a G protein-coupled receptor (KISS1R). KISS1 acts as a metastasis suppressor in numerous human cancers. However, recent studies have demonstrated that an increase in KISS1 and KISS1R expression in patient breast tumors correlates with higher tumor grade and metastatic potential. We have shown that KP-10 stimulates invasion of estrogen receptor α (ERα)-negative MDA-MB-231 breast cancer cells via transactivation of the epidermal growth factor receptor (EGFR). Here, we report that either KP-10 treatment of ERα-negative nonmalignant mammary epithelial MCF10A cells or expression of KISS1R in MCF10A cells induced a mesenchymal phenotype and stimulated invasiveness. Similarly, exogenous expression of KISS1R in ERα-negative SKBR3 breast cancer cells was sufficient to trigger invasion and induced extravasation in vivo. In contrast, KP-10 failed to transactivate EGFR or stimulate invasiveness in the ERα-positive MCF7 and T47D breast cancer cells. This suggested that ERα negatively regulates KISS1R-dependent breast cancer cell migration, invasion, and EGFR transactivation. In support of this, we found that these KP-10-induced effects were ablated upon exogenous expression of ERα in the MDA-MB-231 cells, by down-regulating KISS1R expression. Lastly, we have identified IQGAP1, an actin cytoskeletal binding protein as a novel binding partner of KISS1R, and have shown that KISS1R regulates EGFR transactivation in breast cancer cells in an IQGAP1-dependent manner. Overall, our data strongly suggest that the ERα status of mammary cells dictates whether KISS1R may be a novel clinical target for treating breast cancer metastasis.

  17. 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.

  18. Comparison of hyaluronidase expression, invasiveness and tubule formation promotion in ER (-) and ER (+) breast cancer cell lines in vitro

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-yi; TAN Jin-xiang; Marc Vasse; Bertrand Delpech; REN Guo-sheng

    2009-01-01

    Background Hyaluronidase (Hyase) is an enzyme which hydrolyses hyaluronan (HA), a large nonsulfated glycosaminoglycan. Several genes have been identified to code for hyaluronidases in humans. Its role has only recently been underlined in the invasion of prostate cancer, colonic cancer, and breast cancer. Moreover, the findings were in agreement with some experimental results which showed that HA-derived oligosaccharides had angiogenesis-promoting activity. All these findings prompted us to investigate factors that had been characterized as putative invasive factors in different human breast cancer-derived cell lines.Methods We selected two series of human breast cancer-derived cell lines whose expression of estrogen receptors (ER) was previously published. Hyaluronidase secretion in culture medium and expression of matrix metallo-proteinase (MMP)-9, cathepsin-D (cath-D) and vascular endothelial growth factor (VEGF) by cells were determined. We also investigated cell invasiveness in the Matrigel invasion assay, and studied the capability of cancer cells to promote in vitro formation of tubules by endothelial cells.Results ER(-) cells secreted significantly more hyaluronidase (P <0.001) and expressed significantly more VEGF (P <0.01), MMP-9 (P <0.05) and cath-D (P <0.0001) than ER(+) cells. Invasion through Matdgel by ER(-) Hyase(+) cells was significantly higher than that by ER(+) Hyase(-) cells (P<0.05). In both cases, invasion was decreased by heparin (P <0.05). When ECV-304 endothelial cells were co-cultivated in millicell chambers with cancer cells, ECV-304 cells were induced to form tubules. Tubule formation was demonstrated to be more prominent with ER(-) Hyase(+) cells than with ER(+) Hyase(-) cells (P <0.05).Conclusion Invasive features of ER(-) breast cancer cells can be characterized in vitro by an invasive Matrigel assay,as the induction of tubule formation by ECV-304 endothelial cells, higher secretion of hyaluronidase, and higher expression of

  19. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling.

    Science.gov (United States)

    Sliva, D; Jedinak, A; Kawasaki, J; Harvey, K; Slivova, V

    2008-04-22

    The antitumour activity of a medicinal mushroom Phellinus linteus (PL), through the stimulation of immune system or the induction of apoptosis, has been recently described. However, the molecular mechanisms responsible for the inhibition of invasive behaviour of cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer cells. The growth inhibition of MDA-MB-231 cells is mediated by the cell cycle arrest at S phase through the upregulation of p27(Kip1) expression. Phellinus linteus also suppressed invasive behaviour of MDA-MB-231 cells by the inhibition of cell adhesion, cell migration and cell invasion through the suppression of secretion of urokinase-plasminogen activator from breast cancer cells. In addition, PL markedly inhibited the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells, through the downregulation of secretion of vascular endothelial growth factor from MDA-MB-231 cells. These effects are mediated by the inhibition of serine-threonine kinase AKT signalling, because PL suppressed phosphorylation of AKT at Thr(308) and Ser(473) in breast cancer cells. Taken together, our study suggests potential therapeutic effect of PL against invasive breast cancer.

  20. 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.

  1. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke

    step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between......Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer...

  2. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke

    2015-01-01

    step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between......Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  8. 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.

  9. Glucocorticoids induce CCN5/WISP-2 expression and attenuate invasion in oestrogen receptor-negative human breast cancer cells.

    Science.gov (United States)

    Ferrand, Nathalie; Stragier, Emilien; Redeuilh, Gérard; Sabbah, Michèle

    2012-10-01

    CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 [WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2] is an oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial-mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients.

  10. Subclinical Breast Cancer: Minimally Invasive Approaches. Our Experience with Percutaneous Radiofrequency Ablation vs. Cryotherapy

    Science.gov (United States)

    Manenti, Guglielmo; Scarano, Angela L.; Pistolese, Chiara A.; Perretta, Tommaso; Bonanno, Elena; Orlandi, Augusto; Simonetti, Giovanni

    2013-01-01

    Summary Background The aim of this study was to compare the efficacy of radiofrequency ablation vs. cryoablation in the treatment of early breast cancer. Patients and Methods 80 women (mean age 73 ± 5 years) with early breast cancer were retrospectively evaluated. 40 patients underwent cryoablation and 40 patients underwent radiofrequency ablation, both with sentinel lymph node excision. Tumor volume and histopatological data were compared by means of postprocedural 3.0-T magnetic resonance imaging (MRI). 30–45 days after the percutaneous ablation, all patients underwent surgical resection of the tumor. The mean follow-up was 18 months without any local recurrences. Results Both techniques allow good correlation with histopathological data. In 75 patients (93.8%) we observed complete necrosis; in 5 cases there was residual disease in the postprocedural MRI and postoperative histological examination. There was a good correlation between MRI volume and histologic samples. Cosmetic results were good in all patients but 2. Conclusion Both percutaneous radiofrequency ablation and cryotherapy are minimally invasive techniques with a good clinical and cosmetic outcome in selected cases. MRI examination is an ideal method to assess breast neoplasms in terms of quality and quantity as well as residual tumor extent after percutaneous ablation. Cryotherapy is the preferred method because of the analgesic effect of freezing with better patients compliance. PMID:24415989

  11. Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis.

    Science.gov (United States)

    Wang, Ting; Gilkes, Daniele M; Takano, Naoharu; Xiang, Lisha; Luo, Weibo; Bishop, Corey J; Chaturvedi, Pallavi; Green, Jordan J; Semenza, Gregg L

    2014-08-05

    Extracellular vesicles such as exosomes and microvesicles (MVs) are shed by cancer cells, are detected in the plasma of cancer patients, and promote cancer progression, but the molecular mechanisms regulating their production are not well understood. Intratumoral hypoxia is common in advanced breast cancers and is associated with an increased risk of metastasis and patient mortality that is mediated in part by the activation of hypoxia-inducible factors (HIFs). In this paper, we report that exposure of human breast cancer cells to hypoxia augments MV shedding that is mediated by the HIF-dependent expression of the small GTPase RAB22A, which colocalizes with budding MVs at the cell surface. Incubation of naïve breast cancer cells with MVs shed by hypoxic breast cancer cells promotes focal adhesion formation, invasion, and metastasis. In breast cancer patients, RAB22A mRNA overexpression in the primary tumor is associated with decreased overall and metastasis-free survival and, in an orthotopic mouse model, RAB22A knockdown impairs breast cancer metastasis.

  12. ABL tyrosine kinase inhibition variable effects on the invasive properties of different triple negative breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Clément Chevalier

    Full Text Available The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity in vitro. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of ABL expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.

  13. Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer

    Science.gov (United States)

    2017-02-28

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  14. 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.

  15. Breast Cancer Overview

    Science.gov (United States)

    ... Cancer > Breast Cancer > Breast Cancer: Overview Request Permissions Breast Cancer: Overview Approved by the Cancer.Net Editorial Board , ... bean-shaped organs that help fight infection. About breast cancer Cancer begins when healthy cells in the breast ...

  16. Biological and clinical implications of nicastrin expression in invasive breast cancer.

    Science.gov (United States)

    Filipović, Aleksandra; Gronau, Julian Hendrik; Green, Andrew R; Wang, Jayson; Vallath, Sabari; Shao, Dongmin; Rasul, Sabeena; Ellis, Ian O; Yagüe, Ernesto; Sturge, Justin; Coombes, R Charles

    2011-01-01

    Nicastrin is an essential component of the gamma secretase (GS) enzyme complex, required for its synthesis and recognition of substrates for proteolytic cleavage. The purpose of this study was to investigate whether nicastrin has prognostic value or potential as a therapeutic target in breast cancer (BC). The suitability of nicastrin as a target in BC was assessed using BC tissue microarrays (TMAs) (n = 1050), and its biological role in vitro was evaluated in BC cell lines following gene silencing. Nicastrin blocking antibodies were developed and evaluated for their suitability as potential clinical therapeutics. TMA and cell line analysis confirmed that nicastrin expression was upregulated in BC compared to normal breast cells. In TMA patient samples, high nicastrin expression was observed in 47.5% of cases and correlated with ERα expression, patient age, and tumor grade. In pre-defined subset analysis, high nicastrin expression predicted for worse BC specific survival in the ERα -ve cohort. In vitro gene silencing of nicastrin resulted in disruption of the GS complex and a decrease in notch1 cleavage. This was sufficient to increase E-cadherin expression and its co-localization with p120 catenin at cell-cell junctions in MCF7 cells. Nicastrin silencing in invasive MDA-MB-231 cells resulted in loss of vimentin expression and a marked reduction in both cell motility and invasion; which was concomitant with the de novo formation of cell-cell junctions characterized by the colocalization of p120 catenin and F-actin. These data indicate that nicastrin can function to maintain epithelial to mesenchymal transition during BC progression. Anti-nicastrin polyclonal and monoclonal antibodies were able to decrease notch1 and vimentin expression and reduced the invasive capacity of BC cells in vitro. This supports our hypothesis that a nicastrin blocking antibody could be used to limit metastatic dissemination in invasive BC.

  17. Gli-1 is crucial for hypoxia-induced epithelial-mesenchymal transition and invasion of breast cancer.

    Science.gov (United States)

    Lei, Jianjun; Fan, Lin; Wei, Guangbing; Chen, Xin; Duan, Wanxing; Xu, Qinhong; Sheng, Wei; Wang, Kang; Li, Xuqi

    2015-04-01

    Hypoxia can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, their mechanisms remain unclear. The objective of this study was to evaluate the role of Gli-1, an effector of the Hedgehog pathway, in the hypoxia-induced EMT and invasion of breast cancer cells. Human breast cancer MDA-MB-231 cells were transfected with HIF-1α or Gli-1-specific small interfering RNA (siRNA) and cultured under a normoxic or hypoxic condition. The relative levels of HIF-1α, Gli-1, E-cadherin, and vimentin in the cells were characterized by quantitative RT-PCR and Western blot assays, and the invasion of MDA-MB-231 cells was determined. Data was analyzed by Student T test, one-way ANOVA, and post hoc LSD test or Mann-Whitney U when applicable. We observed that hypoxia significantly upregulated the relative levels of vimentin expression, but downregulated E-cadherin expression and promoted the invasion of MDA-MB-231 cells, associated with upregulated HIF-1α translation and Gil-1 expression. Knockdown of HIF-1α mitigated hypoxia-modulated Gil-1, vimentin and E-cadherin expression, and invasion of MDA-MB-231 cells. Knockdown of Gil-1 did not significantly change hypoxia-upregulated HIF-1α translation but completely eliminated hypoxia-modulated vimentin and E-cadherin expression and invasion of MDA-MB-231 cells. These data indicate that Gil-1 is crucial for hypoxia-induced EMT and invasion of breast cancer cells and may be a therapeutic target for intervention of breast cancer metastasis.

  18. Breast Cancer

    Science.gov (United States)

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

  19. 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.

  20. 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

    test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian...... 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...

  1. 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.

  2. NEDD9 is a positive regulator of epithelial-mesenchymal transition and promotes invasion in aggressive breast cancer.

    Directory of Open Access Journals (Sweden)

    Chenfei Kong

    Full Text Available Epithelial to mesenchymal transition (EMT plays an important role in many biological processes. The latest studies revealed that aggressive breast cancer, especially the triple-negative breast cancer (TNBC subtype was frequently associated with apparent EMT, but the mechanisms are still unclear. NEDD9/HEF1/Cas-L is a member of the Cas protein family and was identified as a metastasis marker in multiple cancer types. In this study, we wished to discern the role of NEDD9 in breast cancer progression and to investigate the molecular mechanism by which NEDD9 regulates EMT and promotes invasion in triple-negative breast cancer. We showed that expression of NEDD9 was frequently upregulated in TNBC cell lines, and in aggressive breast tumors, especially in TNBC subtype. Knockdown of endogenous NEDD9 reduced the migration, invasion and proliferation of TNBC cells. Moreover, ectopic overexpression of NEDD9 in mammary epithelial cells led to a string of events including the trigger of EMT, activation of ERK signaling, increase of several EMT-inducing transcription factors and promotion of their interactions with the E-cadherin promoter. Data presented in this report contribute to the understanding of the mechanisms by which NEDD9 promotes EMT, and provide useful clues to the evaluation of the potential of NEDD9 as a responsive molecular target for TNBC chemotherapy.

  3. 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

  4. Surgery for Breast Cancer

    Science.gov (United States)

    ... Cancer During Pregnancy Breast Cancer Breast Cancer Treatment Surgery for Breast Cancer Surgery is a common treatment ... removed (breast reconstruction) Relieve symptoms of advanced cancer Surgery to remove breast cancer There are two main ...

  5. 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.

  6. The Contribution of Risk Factors to the Higher Incidence of Invasive and In Situ Breast Cancers in Women With Higher Levels of Education in the European Prospective Investigation Into Cancer and Nutrition

    NARCIS (Netherlands)

    Menvielle, Gwenn; Kunst, Anton E.; van Gils, Carla H.; Peeters, Petra H.; Boshuizen, Hendriek; Overvad, Kim; Olsen, Anja; Tjonneland, Anne; Hermann, Silke; Kaaks, Rudolf; Bergmann, Manuela M.; Illner, Anne-Kathrin; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Palli, Domenico; Berrino, Franco; Mattiello, Amelia; Tumino, Rosario; Sacerdote, Carlotta; May, Anne; Monninkhof, Evelyn; Braaten, Tonje; Lund, Eiliv; Ramon Quiros, Jose; Duell, Eric J.; Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Borgquist, Signe; Manjer, Jonas; Khaw, Kay Tee; Allen, Naomi E.; Reeves, Gillian K.; Chajes, Veronique; Rinaldi, Sabina; Slimani, Nadia; Gallo, Valentina; Vineis, Paolo; Riboli, Elio; Bueno-de-Mesquita, H. Bas

    2011-01-01

    The authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasive breast ca

  7. Axillary ultrasound and fine-needle aspiration in preoperative staging of axillary lymph nodes in patients with invasive breast cancer*

    Science.gov (United States)

    Rocha, Rafael Dahmer; Girardi, André Ricardo; Pinto, Renata Reis; de Freitas, Viviane Aguilera Rolim

    2015-01-01

    Objective To propose an algorithm to determine the necessity for ultrasonography-guided fine-needle aspiration (US-FNA) in preoperative axillary lymph node staging of patients with invasive breast cancer. Materials and Methods Prospective study developed at National Cancer Institute. The study sample included 100 female patients with breast cancer referred for axillary staging by US-FNA. Results The overall US-FNA sensitivity was set at 79.4%. The positive predictive value was calculated to be 100%, and the negative predictive value, 69.5%. The US-FNA sensitivity for lymph nodes with normal sonographic features was 0%, while for indeterminate lymph nodes it was 80% and, for suspicious lymph nodes, 90.5%. In the assessment of invasive breast tumors stages T1, T2 and T3, the sensitivity was respectively 69.6%, 83.7% and 100%. US-FNA could avoid sentinel node biopsy in 54% of cases. Conclusion Axillary ultrasonography should be included in the preoperative staging of all patients with invasive breast cancer. The addition of US-FNA in cases of lymph nodes suspicious for malignancy may prevent more than 50% of sentinel lymphadenectomies, significantly shortening the time interval to definitive therapy. PMID:26811550

  8. 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

  9. 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...... of the corresponding orthotopic xenograft tumors. Further studies indicated that the glucocorticoid dexamethasone and the highly potent class I histone deacetylase (HDAC) inhibitor largazole cooperated to induce E-cadherin localization to the plasma membrane in triple-negative breast cancers, and to suppress cellular...

  10. 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...

  11. Loss of cadherin-based cell adhesion and the progression of Invasive Lobular Breast Cancer

    NARCIS (Netherlands)

    Vlug, E.J.

    2015-01-01

    Lobular breast cancer is a type of breast cancer that is histologically characterized by a noncohesive growth pattern of small regular cells, where single cells infiltrate as one-layered strands of cells. This noncohesive growth pattern is due to inactivation of the E-cadherin complex and a subseque

  12. Tumour characteristics and survival in patients with invasive interval breast cancer classified according to mammographic findings at the latest screening

    DEFF Research Database (Denmark)

    Vitak, B; Olsen, K E; Månson, J C;

    1999-01-01

    rate of patients with interval cancer and the interval between the latest screen and diagnosis, tumour characteristics and radiological category of the interval tumours. The study focused on comparison of patients with true interval and missed interval cancer. Women with mammographically occult tumours...... screen and diagnosis were not genuine predictors of the prognosis in patients with invasive interval breast cancer. No certain prognostic difference existed between true interval cancers and overlooked or misinterpreted interval breast cancers, despite higher proportions of grade-I tumours, ER positive......The aim of this study was to investigate whether different mammographic categories of interval cancer classified according to findings at the latest screening are associated with different distributions of prognostic factors or with different survival rates. The series consisted of all patients...

  13. Alcohol promotes migration and invasion of triple-negative breast cancer cells through activation of p38 MAPK and JNK.

    Science.gov (United States)

    Zhao, Ming; Howard, Erin W; Parris, Amanda B; Guo, Zhiying; Zhao, Qingxia; Yang, Xiaohe

    2017-03-01

    Although alcohol is an established breast cancer risk factor, the underlying mechanisms remain unclear. Previous studies examined the general association between alcohol consumption and breast cancer risk; however, the risk for different breast cancer subtypes has been rarely reported. Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking hormone receptors and HER2 expression, and having poor prognosis. Understanding the molecular mechanisms of TNBC etiology remains a significant challenge. In this study, we investigated cellular responses to alcohol in two TNBC cell lines, MDA-MB-231 and MDA-MB-468. Our results showed that alcohol at low concentrations (0.025-0.1% v/v) induced cell proliferation, migration, and invasion in 1% FBS-containing medium. Molecular analysis indicated that these phenotypic changes were associated with alcohol-induced reactive oxygen species production and increased p38 and JNK phosphorylation. Likewise, p38 or JNK inhibition attenuated alcohol-induced cell migration and invasion. We revealed that alcohol treatment activated/phosphorylated NF-κB regulators and increased transcription of NF-κB-targeted genes. While examining the role of acetaldehyde, the major alcohol metabolite, in alcohol-associated responses in TNBC cells, we saw that acetaldehyde induced cell migration, invasion, and increased phospho-p38, phospho-JNK, and phospho-IκBα in a pattern similar to alcohol treatment. Taken together, we established that alcohol promotes TNBC cell proliferation, migration, and invasion in vitro. The underlying mechanisms involve the induction of oxidative stress and the activation of NF-κB signaling. In particular, the activation of p38 and JNK plays a pivotal role in alcohol-induced cellular responses. These results will advance our understanding of alcohol-mediated development and promotion of TNBC. © 2016 Wiley Periodicals, Inc.

  14. Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

    Directory of Open Access Journals (Sweden)

    Kung Hsiang-Fu

    2011-01-01

    Full Text Available Abstract Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1 acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs, whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs. Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these

  15. Phosphatidylinositol 4-phosphate in the Golgi apparatus regulates cell-cell adhesion and invasive cell migration in human breast cancer.

    Science.gov (United States)

    Tokuda, Emi; Itoh, Toshiki; Hasegawa, Junya; Ijuin, Takeshi; Takeuchi, Yukiko; Irino, Yasuhiro; Fukumoto, Miki; Takenawa, Tadaomi

    2014-06-01

    Downregulation of cell-cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell-cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4)P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4)P phosphatase localized in the Golgi apparatus, resulted in decreased cell-cell adhesion and increased cell migration in weakly invasive cells. In contrast, silencing phosphatidylinositol 4-kinase IIIβ, which generates PI(4)P in the Golgi apparatus, increased cell-cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI(4)P effector, Golgi phosphoprotein 3, was found to be involved in the generation of these phenotypes in a manner that depends on its PI(4)P-binding ability. Our results provide a new model for breast cancer cell progression in which progression is controlled by PI(4)P levels in the Golgi apparatus.

  16. Breast Cancer Invasion and Metastasis by mPRα Through the PI3K/Akt Signaling Pathway.

    Science.gov (United States)

    Wu, Xiaojuan; Sun, Limin; Wang, Xiao; Su, Peng; Li, Zhishuang; Zhang, Chunyan; Wang, Yan; Gao, Peng; Ma, Rong

    2016-07-01

    Invasive breast cancer is the most common type of malignancy in women worldwide. However, the mechanism responsible for breast cancer metastasis is still unclear and needs further illustration. It has been proven that matrix metallopeptidase 9 (MMP-9) promotes metastasis of the cancer cells. However, the interaction between mPRα and MMP-9 has not been studied. Therefore, in the present research, the effect of MMP-9 on the malignant progression of invasive breast cancer promoted by membrane progesterone receptorα (mPRα) was investigated. The results showed that the protein expression of mPRα, p-Akt and MMP-9 increased in the cancerous tissues compared to that of the noncancerous breast tissue. Furthermore, a positive correlation was found between mPRα and C-erbB-2, as well as the number of involved local lymph nodes. On the other hand, a negative correlation was observed between mPRα and estrogen receptors (ER) along with progesterone receptors (PR). Similarly, a positive association was found between MMP-9 and the number of involved local lymph nodes. Besides, the high expression of MMP-9 also had a positive correlation with the tumor size. However, the high level of MMP-9 had a negative correlation with ER and PR. In addition, there was a positive correlation between mPRα and p-Akt together with MMP-9. The results confirm that mPRα was a major marker of harmful prognosis and it promoted the expression of MMP-9 during invasion to the local lymph nodes through the pathway of PI3K/Akt. The present study provided a novel therapeutic strategy to inhibit breast cancer growth by preventing mPRα signaling pathway.

  17. 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.)

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Evaluation of aqueous extracts of Taraxacum officinale on growth and invasion of breast and prostate cancer cells.

    Science.gov (United States)

    Sigstedt, Sophia C; Hooten, Carla J; Callewaert, Manika C; Jenkins, Aaron R; Romero, Anntherese E; Pullin, Michael J; Kornienko, Alexander; Lowrey, Timothy K; Slambrouck, Severine Van; Steelant, Wim F A

    2008-05-01

    Ethnotraditional use of plant-derived natural products plays a significant role in the discovery and development of potential medicinal agents. Plants of the genus Taraxacum, commonly known as dandelions, have a history of use in Chinese, Arabian and Native American traditional medicine, to treat a variety of diseases including cancer. To date, however, very few studies have been reported on the anti-carcinogenic activity of Taraxacum officinale (TO). In the present study, three aqueous extracts were prepared from the mature leaves, flowers and roots, and investigated on tumor progression related processes such as proliferation and invasion. Our results show that the crude extract of dandelion leaf (DLE) decreased the growth of MCF-7/AZ breast cancer cells in an ERK-dependent manner, whereas the aqueous extracts of dandelion flower (DFE) and root (DRE) had no effect on the growth of either cell line. Furthermore, DRE was found to block invasion of MCF-7/AZ breast cancer cells while DLE blocked the invasion of LNCaP prostate cancer cells, into collagen type I. Inhibition of invasion was further evidenced by decreased phosphorylation levels of FAK and src as well as reduced activities of matrix metalloproteinases, MMP-2 and MMP-9. This study provides new scientific data on TO and suggests that TO extracts or individual components present in the extracts may be of value as novel anti-cancer agents.

  3. Curcumin inhibits LPA-induced invasion by attenuating RhoA/ROCK/MMPs pathway in MCF7 breast cancer cells.

    Science.gov (United States)

    Sun, Kai; Duan, Xiaoyi; Cai, Hui; Liu, Xiaohong; Yang, Ya; Li, Min; Zhang, Xiaoyun; Wang, Jiansheng

    2016-02-01

    Breast cancer generally shows poor prognosis because of its invasion and metastasis. Lysophosphatidic acid (LPA) induces and aggravates cancer invasion and metastasis by activating its downstream signal pathways. RhoA/ROCK/MMP signaling was found one of the LPA-induced pathways, which may be involved in invasion of breast cancer. Furthermore, we investigated whether this pathway was involved in curcumin's effect against LPA-induced invasion. LPA incubation was used to enhance invasion of MCF-7 breast cancer cells. RhoA expression was knocked-down by siRNA technique. MTT assay was used to evaluate the proliferation. Transwell assay was utilized to investigate the invasion ability of MCF-7 cells. Real-time PCR and Western blotting were used to assess the expressions of RhoA, ROCK1, ROCK2, MMP2 and MMP9 at both translational and transcriptional levels. The RhoA and ROCK activities were also evaluated. LPA incubation significantly boosted invasion rate of MCF-7. RhoA silencing by siRNA dramatically inhibited LPA-enhanced invasion. Concurrently, RhoA and ROCK activities and expression levels of RhoA, ROCK1, ROCK2, MMP2 and MMP9 were down-regulated by RhoA siRNA transfection. In order to avoid influence of cytotoxicity of curcumin, concentrations below 45 μmol/L were selected to further investigate the mechanism of curcumin's anti-invasion effect. Invasion of LPA-incubated MCF-7 cells was impaired by curcumin in a concentration-dependent manner. Concurrently, RhoA and ROCK activities and expression levels of RhoA, ROCK1, ROCK2, MMP2 and MMP9 were down-regulated by curcumin in a concentration-dependent manner. In conclusion, RhoA/ROCK/MMPs pathway activation is involved in LPA-induced invasion in MCF-7 cells; curcumin inhibited LPA-induced invasion in MCF-7 cells by attenuating RhoA/ROCK/MMPs pathway.

  4. 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.

  5. Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Joe Tien

    Full Text Available This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.

  6. 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.

  7. 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.

  8. 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.

  9. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    JuhuaZhou; YinZhong

    2004-01-01

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

  10. Breast Cancer 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.

  11. 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...... 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...

  12. Breast cancer screening

    Science.gov (United States)

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

  13. 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.

  14. 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.

  15. 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

  16. Induction of Wnt-inducible signaling protein-1 correlates with invasive breast cancer oncogenesis and reduced type 1 cell-mediated cytotoxic immunity: a retrospective study.

    Science.gov (United States)

    Klinke, David J

    2014-01-01

    Innate and type 1 cell-mediated cytotoxic immunity function as important extracellular control mechanisms that maintain cellular homeostasis. Interleukin-12 (IL12) is an important cytokine that links innate immunity with type 1 cell-mediated cytotoxic immunity. We recently observed in vitro that tumor-derived Wnt-inducible signaling protein-1 (WISP1) exerts paracrine action to suppress IL12 signaling. The objective of this retrospective study was three fold: 1) to determine whether a gene signature associated with type 1 cell-mediated cytotoxic immunity was correlated with overall survival, 2) to determine whether WISP1 expression is increased in invasive breast cancer, and 3) to determine whether a gene signature consistent with inhibition of IL12 signaling correlates with WISP1 expression. Clinical information and mRNA expression for genes associated with anti-tumor immunity were obtained from the invasive breast cancer arm of the Cancer Genome Atlas study. Patient cohorts were identified using hierarchical clustering. The immune signatures associated with the patient cohorts were interpreted using model-based inference of immune polarization. Reverse phase protein array, tissue microarray, and quantitative flow cytometry in breast cancer cell lines were used to validate observed differences in gene expression. We found that type 1 cell-mediated cytotoxic immunity was correlated with increased survival in patients with invasive breast cancer, especially in patients with invasive triple negative breast cancer. Oncogenic transformation in invasive breast cancer was associated with an increase in WISP1. The gene expression signature in invasive breast cancer was consistent with WISP1 as a paracrine inhibitor of type 1 cell-mediated immunity through inhibiting IL12 signaling and promoting type 2 immunity. Moreover, model-based inference helped identify appropriate immune signatures that can be used as design constraints in genetically engineering better pre

  17. 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.

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bargalló, Xavier, E-mail: xbarga@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Santamaría, Gorane, E-mail: gsanta@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Velasco, Martín, E-mail: mvelasco@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Amo, Montse del, E-mail: mdelamo@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Arguis, Pedro, E-mail: parguis@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Burrel, Marta, E-mail: mburrel@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Capurro, Sebastian, E-mail: scapurro@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain)

    2012-10-15

    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.

  20. Breast Cancer Research Update

    Science.gov (United States)

    ... JavaScript on. Feature: Breast Cancer Breast Cancer Research Update Winter 2017 Table of Contents National Cancer Institute ... Addressing Breast Cancer's Unequal Burden / Breast Cancer Research Update Winter 2017 Issue: Volume 11 Number 4 Page ...

  1. 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

  2. The Role of MicroRNAs in Breast Cancer Migration, Invasion and Metastasis

    Directory of Open Access Journals (Sweden)

    Joy Tang

    2012-10-01

    Full Text Available MicroRNAs (miRNAs are a major class of small, noncoding RNA molecules that regulate gene expression by targeting mRNAs to trigger either translational repression or mRNA degradation. They have recently been more widely investigated due to their potential role as targets for cancer therapy. Many miRNAs have been implicated in several human cancers, including breast cancer. miRNAs are known to regulate cell cycle and development, and thus may serve as useful targets for exploration in anticancer therapeutics. The link between altered miRNA signatures and breast cancer development and metastasis can be observed either through the loss of tumor suppressor miRNAs, such as let-7s, miR-30a/31/34a/125s/200s/203/205/206/342 or the overexpression of oncogenic miRNAs, such as miR-10b/21/135a/155/221/222/224/373/520c in breast cancer cells. Some of these miRNAs have also been validated in tumor specimens of breast cancer patients, underscoring their potential roles in diagnostics, as well as targets for novel therapeutics for breast cancer. In this review article, we will provide an overview and update of our current understanding of the mode of action of several of these well characterized miRNAs in breast cancer models. Therefore, better understanding of the gene networks orchestrated by these miRNAs may help exploit the full potential of miRNAs in regards to cancer diagnosis, treatment, and therapeutics.

  3. 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.

  4. Paired ductal carcinoma in situ and invasive breast cancer lesions in the D-loop of the mitochondrial genome indicate a cancerization field effect.

    Science.gov (United States)

    Maggrah, Andrea; Robinson, Kerry; Creed, Jennifer; Wittock, Roy; Gehman, Ken; Gehman, Teresa; Brown, Helen; Harbottle, Andrew; Froberg, M Kent; Klein, Daniel; Reguly, Brian; Parr, Ryan

    2013-01-01

    Alterations in the mitochondrial genome have been chronicled in most solid tumors, including breast cancer. The intent of this paper is to compare and document somatic mitochondrial D-loop mutations in paired samples of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) indicating a potential breast ductal epithelial cancerization field effect. Paired samples of these histopathologies were laser-captured microdissected (LCM) from biopsy, lumpectomy, and mastectomy tissues. Blood samples were collected as germplasm control references. For each patient, hypervariable region 1 (HV1) in the D-loop portion of the mitochondrial genome (mtGenome) was sequenced for all 3 clinical samples. Specific parallel somatic heteroplasmic alterations between these histopathologies, particularly at sites 16189, 16223, 16224, 16270, and 16291, suggest the presence of an epithelial, mitochondrial cancerization field effect. These results indicate that further characterization of the mutational pathway of DCIS and IBC may help establish the invasive potential of DCIS. Moreover, this paper indicates that biofluids with low cellularity, such as nipple aspirate fluid and/or ductal lavage, warrant further investigation as early and minimally invasive detection mediums of a cancerization field effect within breast tissue.

  5. Paired Ductal Carcinoma In Situ and Invasive Breast Cancer Lesions in the D-Loop of the Mitochondrial Genome Indicate a Cancerization Field Effect

    Directory of Open Access Journals (Sweden)

    Andrea Maggrah

    2013-01-01

    Full Text Available Alterations in the mitochondrial genome have been chronicled in most solid tumors, including breast cancer. The intent of this paper is to compare and document somatic mitochondrial D-loop mutations in paired samples of ductal carcinoma in situ (DCIS and invasive breast cancer (IBC indicating a potential breast ductal epithelial cancerization field effect. Paired samples of these histopathologies were laser-captured microdissected (LCM from biopsy, lumpectomy, and mastectomy tissues. Blood samples were collected as germplasm control references. For each patient, hypervariable region 1 (HV1 in the D-loop portion of the mitochondrial genome (mtGenome was sequenced for all 3 clinical samples. Specific parallel somatic heteroplasmic alterations between these histopathologies, particularly at sites 16189, 16223, 16224, 16270, and 16291, suggest the presence of an epithelial, mitochondrial cancerization field effect. These results indicate that further characterization of the mutational pathway of DCIS and IBC may help establish the invasive potential of DCIS. Moreover, this paper indicates that biofluids with low cellularity, such as nipple aspirate fluid and/or ductal lavage, warrant further investigation as early and minimally invasive detection mediums of a cancerization field effect within breast tissue.

  6. 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...

  7. Breast cancer statistics, 2011.

    Science.gov (United States)

    DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

    2011-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population.

  8. Triple-negative invasive breast cancer on dynamic contrast-enhanced and diffusion-weighted MR imaging: comparison with other breast cancer subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Youk, Ji Hyun; Son, Eun Ju; Chung, Jin; Kim, Jeong-Ah; Kim, Eun-kyung [Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-08-15

    To determine the MRI features of triple-negative invasive breast cancer (TNBC) on dynamic contrast-enhanced MR imaging (DCE-MRI) and diffusion-weighted MR imaging (DWI) in comparison with ER-positive/HER2-negative (ER+) and HER2-positive cancer (HER2+). A total of 271 invasive cancers in 269 patients undergoing preoperative MRI and surgery were included. Two radiologists retrospectively assessed morphological and kinetic characteristics on DCE-MRI and tumour detectability on DWI. Apparent diffusion coefficient (ADC) values of lesions were measured. Clinical and MRI features of the three subtypes were compared. Compared with ER+ (n = 119) and HER2+ (n = 94), larger size, round/oval mass shape, smooth mass margin, and rim enhancement on DCE-MRI were significantly associated with TNBC (n = 58; P < 0.0001). On DWI, mean ADC value (x 10{sup -3} mm{sup 2}/s) of TNBC (1.03) was higher than the mean ADC values for ER+ and HER2+ (0.89 and 0.84; P < 0.0001). There was no difference in tumour detectability (P = 0.099). Tumour size (P = 0.009), mass margin (smooth, P < 0.0001; irregular, P = 0.020), and ADC values (P = 0.002) on DCE-MRI and DWI were independent features of TNBC. In addition to the morphological features, higher ADC values on DWI were independently associated with TNBC and could be useful in differentiating TNBC from ER+ and HER2+. (orig.)

  9. 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.

  10. 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...... 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...

  11. MicroRNA-340 inhibits the migration, invasion, and metastasis of breast cancer cells by targeting Wnt pathway.

    Science.gov (United States)

    Mohammadi-Yeganeh, Samira; Paryan, Mahdi; Arefian, Ehsan; Vasei, Mohammad; Ghanbarian, Hossein; Mahdian, Reza; Karimipoor, Morteza; Soleimani, Masoud

    2016-07-01

    MicroRNAs (miRNAs) play a key role in tumor metastasis based on their capacity to regulate the expression of tumor-related genes. Over-expression of key genes such as c-MYC and CTNNB1 (encoding β-catenin) in Wnt/β-catenin-dependent and ROCK1 in Wnt/β-catenin-independent signaling pathways (Rho/Rho-associated kinase (ROCK) signaling pathway) has already been identified as the hallmarks of many tumors, and their role in breast cancer has also been investigated and confirmed. miR-340 characterization as an onco-suppressor miRNA has been previously reported. However, the mechanism by which it inhibits metastasis has not been completely elucidated. Quantitative real-time PCR (qPCR), Western blot, and luciferase assays were used to confirm the effect of miR-340 on the 3'-untranslated region (UTR) of the target genes. Lentiviral particles containing miR-340 were also used to evaluate the effect of miR-340 restoration on cell proliferation, migration, and invasion in vitro in the invasive MDA-MB-231 cell line. By applying bioinformatic approaches for the prediction of miRNAs targeting 3'-UTRs of CTNNB1, c-MYC, and ROCK1, we found out that miR-340 could dramatically down-regulate metastasis by targeting Wnt signaling in breast cancer cells. In the current study, analyzing miR-340 by reverse transcription quantitative PCR (RT-qPCR) in MDA-MB-231 showed that it was remarkably down-regulated in the metastatic breast cancer cell line. We found that restoration of miR-340 in the invasive breast cancer cell line, MDA-MB-231, suppresses the expression of the target genes' messenger RNA (mRNA) and protein and, as a result, inhibits tumor cell invasion and metastasis. Our findings highlight the ability of bioinformatic approaches to find miRNAs targeting specific genes. By bioinformatic analysis, we confirmed the important role of miR-340 as a pivotal regulator of breast cancer metastasis in targeting previously validated (ROCK1) and potentially novel genes, i.e., (CTNNB1 and c-MYC).

  12. Loss of GM130 in breast cancer cells and its effects on cell migration, invasion and polarity.

    Science.gov (United States)

    Baschieri, Francesco; Uetz-von Allmen, Edith; Legler, Daniel F; Farhan, Hesso

    2015-01-01

    Spatially distinct pools of the small GTPase Cdc42 were observed, but the major focus of research so far has been to investigate its signaling at the plasma membrane. We recently showed that the Golgi pool of Cdc42 is relevant for cell polarity and that it is regulated by GM130, a Golgi matrix protein. Loss of GM130 abrogated cell polarity and consistent with the notion that polarity is frequently impaired in cancer, we found that GM130 is downregulated in colorectal cancer. Whether the loss of GM130 solely affects polarity, or whether it affects other processes relevant for tumorigenesis remains unclear. In a panel of breast cancer cells lines, we investigated the consequences of GM130 depletion on traits of relevance for tumor progression, such as survival, proliferation, adhesion, migration and invasion. We show that cellular assays that depend on polarity, such as chemotaxis and wound scratch assays, are only of limited use to investigate the role of polarity modulators in cancer. Depletion of GM130 increases cellular velocity and increases the invasiveness of breast cancer cells, therefore supporting the view that alterations of polarity contribute to tumor progression.

  13. Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

    Science.gov (United States)

    2015-11-01

    mediated invasion through noncovalent interaction with α5β1 receptors of SUM149PT and MDA-MB-231 metastatic human breast cancer cells, and laid the...foundation for detailed structure–activity relationship (SAR) studies for both peptides as inhibitors of α5β1– mediated metastatic breast cancer invasion...100,000–fold more potent than PHSCN at blocking α5β1– mediated invasion. Furthermore, inclusion of a total of 8 (acetylated) Ac-PhScNGGK sequences on a

  14. Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules

    OpenAIRE

    Vasse, M.; Thibout, D; Paysant, J; Legrand, E.; Soria, C.; Crépin, M

    2001-01-01

    Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM o...

  15. 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).

  16. 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, ...

  17. 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.

  18. Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Simon Turcotte

    2007-10-01

    Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

  19. MicroRNA-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Jiang, Qian; He, Miao; Guan, Shu; Ma, Mengtao; Wu, Huizhe; Yu, Zhaojin; Jiang, Longyang; Wang, Yan; Zong, Xingyue; Jin, Feng; Wei, Minjie

    2016-04-01

    Wnt/β-catenin signaling pathway plays a major role in the cancer metastasis. Several microRNAs (miRNAs) are contributed to the inhibition of breast cancer metastasis. Here, we attempted to find novel targets and mechanisms of microRNA-100 (miR-100) in regulating the migration and invasion of breast cancer cells. In this study, we found that miR-100 expression was downregulated in human breast cancer tissues and cell lines. The overexpression of miR-100 inhibited the migration and invasion of MDA-MB-231 breast cancer cells. Inversely, the downregulation of miR-100 increased the migration and invasion of MCF-7 breast cancer cells. Furthermore, FZD-8, a receptor of Wnt/β-catenin signaling pathway, was demonstrated a direct target of miR-100. The overexpression of miR-100 decreased the expression levels not only FZD-8 but also the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteniase-7 (MMP-7), T-cell factor-4 (TCF-4), and lymphoid enhancing factor-1 (LEF-1), and increased the protein expression levels of GSK-3β and p-GSK-3β in MDA-MB-231 cells, and the transfection of miR-100 inhibitor in MCF-7 cells showed the opposite effects. In addition, the expression of miR-100 was negatively correlated with the FZD-8 expression in human breast cancer tissues. Overall, these findings suggest that miR-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway and manipulation of miR-100 may provide a promoting therapeutic strategy for cancer breast treatment.

  20. High-throughput RNAi screening for novel modulators of vimentin expression identifies MTHFD2 as a regulator of breast cancer cell migration and invasion.

    Science.gov (United States)

    Lehtinen, Laura; Ketola, Kirsi; Mäkelä, Rami; Mpindi, John-Patrick; Viitala, Miro; Kallioniemi, Olli; Iljin, Kristiina

    2013-01-01

    Vimentin is an intermediate filament protein, with a key role in the epithelial to mesenchymal transition as well as cell invasion, and it is often upregulated during cancer progression. However, relatively little is known about its regulation in cancer cells. Here, we performed an RNA interference screen followed by protein lysate microarray analysis in bone metastatic MDA-MB-231(SA) breast cancer cells to identify novel regulators of vimentin expression. Out of the 596 genes investigated, three novel vimentin regulators EPHB4, WIPF2 and MTHFD2 were identified. The reduced vimentin expression in response to EPHB4, WIPF2 and MTHFD2 silencing was observed at mRNA and protein levels. Bioinformatic analysis of gene expression data across cancers indicated overexpression of EPHB4 and MTHFD2 in breast cancer and high expression associated with poor clinical characteristics. Analysis of 96 cDNA samples derived from both normal and malignant human tissues suggested putative association with metastatic disease. MTHFD2 knockdown resulted in impaired cell migration and invasion into extracellular matrix as well as decreased the fraction of cells with a high CD44 expression, a marker of cancer stem cells. Furthermore, MTHFD2 expression was induced in response to TGF-β stimulation in breast cancer cells. Our results show that MTHFD2 is overexpressed in breast cancer, associates with poor clinical characteristics and promotes cellular features connected with metastatic disease, thus implicating MTHFD2 as a potential drug target to block breast cancer cell migration and invasion.

  1. 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.

  2. Expression of beclin-1 in the microenvironment of invasive ductal carcinoma of the breast: correlation with prognosis and the cancer-stromal interaction.

    Directory of Open Access Journals (Sweden)

    Akemi Morikawa

    Full Text Available We examined the pathobiological properties of beclin-1, which is a key regulator of autophagosome formation in invasive ductal carcinoma of the breast, with a particular focus on the cancer microenvironment. Immunohistochemistry demonstrated that cancer cells and stromal mesenchymal cells expressed beclin-1 in 68 and 38 of 115 invasive ductal cancers, respectively. Expression of beclin-1 in cancer or stromal cells alone did not correlate with patient prognosis. In contrast, loss of beclin-1 in cancer cells and overexpression in stromal mesenchymal cells was associated with local cancer recurrence, postoperative lymph node metastasis, and a poor disease-free survival rate. A comprehensive gene expression analysis was performed on a co-culture of breast cancer cells and mesenchymal stromal cells, that latter of which either expressed beclin-1 or was depleted of beclin-1 by siRNA. Notably, siRNA-mediated downregulation of beclin-1 in mesenchymal cells co-cultured with breast cancer cells decreased the levels of various pro-inflammatory cytokines, their receptors, and collagen receptors. Quantitative reverse transcription polymerase chain reaction analysis confirmed that reduction of stromal beclin-1 expression decreased the expression of IL-1β and collagen receptor discoidin domain receptor 2 (DDR2. Microenvironmental IL-1β is believed to play an important role in tumor invasion. Recent work has also indicated that overexpression of DDR2 contributes to breast cancer invasion and lymph node metastasis. Taken together, these findings indicate beclin-1 expression in the stroma might be important for shaping the breast cancer microenvironment and thus could be a potent molecular target in patients with invasive ductal carcinoma of the breast.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Salvianolic acid A reverses the paclitaxel resistance and inhibits the migration and invasion abilities of human breast cancer cells by inactivating transgelin 2.

    Science.gov (United States)

    Zheng, Xiaowei; Chen, Siying; Yang, Qianting; Cai, Jiangxia; Zhang, Weipeng; You, Haisheng; Xing, Jianfeng; Dong, Yalin

    2015-01-01

    Multidrug resistance and tumor migration and invasion are the major obstacles to effective breast cancer chemotherapy, but the underlying molecular mechanisms remain unclear. This study investigated the potential of transgelin 2 and salvianolic acid A to modulate the resistance and the migration and invasion abilities of paclitaxel-resistant human breast cancer cells (MCF-7/PTX). MCF-7/PTX cells were found to exhibit not only a high degree of resistance to paclitaxel, but also strong migration and invasion abilities. Small interfering RNA-mediated knockdown of TAGLN2 sensitized the MCF-7/PTX cells to paclitaxel, and inhibited their migration and invasion abilities. In addition, we also observed that combined salvianolic acid A and paclitaxel treatment could reverse paclitaxel resistance, markedly inhibit tumor migration and invasion, and suppress the expression of transgelin 2 in MCF-7/PTX cells. These findings indicate that salvianolic acid A can reverse the paclitaxel resistance and inhibit the migration and invasion abilities of human breast cancer cells by down-regulating the expression of transgelin 2, and hence could be useful in breast cancer treatments.

  8. Salvianolic acid A reverses the paclitaxel resistance and inhibits the migration and invasion abilities of human breast cancer cells by inactivating transgelin 2

    Science.gov (United States)

    Zheng, Xiaowei; Chen, Siying; Yang, Qianting; Cai, Jiangxia; Zhang, Weipeng; You, Haisheng; Xing, Jianfeng; Dong, Yalin

    2015-01-01

    Multidrug resistance and tumor migration and invasion are the major obstacles to effective breast cancer chemotherapy, but the underlying molecular mechanisms remain unclear. This study investigated the potential of transgelin 2 and salvianolic acid A to modulate the resistance and the migration and invasion abilities of paclitaxel-resistant human breast cancer cells (MCF-7/PTX). MCF-7/PTX cells were found to exhibit not only a high degree of resistance to paclitaxel, but also strong migration and invasion abilities. Small interfering RNA-mediated knockdown of TAGLN2 sensitized the MCF-7/PTX cells to paclitaxel, and inhibited their migration and invasion abilities. In addition, we also observed that combined salvianolic acid A and paclitaxel treatment could reverse paclitaxel resistance, markedly inhibit tumor migration and invasion, and suppress the expression of transgelin 2 in MCF-7/PTX cells. These findings indicate that salvianolic acid A can reverse the paclitaxel resistance and inhibit the migration and invasion abilities of human breast cancer cells by down-regulating the expression of transgelin 2, and hence could be useful in breast cancer treatments PMID:26176734

  9. Activity of plasma membrane V-ATPases is critical for the invasion of MDA-MB231 breast cancer cells.

    Science.gov (United States)

    Cotter, Kristina; Capecci, Joseph; Sennoune, Souad; Huss, Markus; Maier, Martin; Martinez-Zaguilan, Raul; Forgac, Michael

    2015-02-06

    The vacuolar (H(+))-ATPases (V-ATPases) are a family of ATP-driven proton pumps that couple ATP hydrolysis with translocation of protons across membranes. Previous studies have implicated V-ATPases in cancer cell invasion. It has been proposed that V-ATPases participate in invasion by localizing to the plasma membrane and causing acidification of the extracellular space. To test this hypothesis, we utilized two separate approaches to specifically inhibit plasma membrane V-ATPases. First, we stably transfected highly invasive MDA-MB231 cells with a V5-tagged construct of the membrane-embedded c subunit of the V-ATPase, allowing for extracellular expression of the V5 epitope. We evaluated the effect of addition of a monoclonal antibody directed against the V5 epitope on both V-ATPase-mediated proton translocation across the plasma membrane and invasion using an in vitro Matrigel assay. The addition of anti-V5 antibody resulted in acidification of the cytosol and a decrease in V-ATPase-dependent proton flux across the plasma membrane in transfected but not control (untransfected) cells. These results demonstrate that the anti-V5 antibody inhibits activity of plasma membrane V-ATPases in transfected cells. Addition of the anti-V5 antibody also inhibited in vitro invasion of transfected (but not untransfected) cells. Second, we utilized a biotin-conjugated form of the specific V-ATPase inhibitor bafilomycin. When bound to streptavidin, this compound cannot cross the plasma membrane. Addition of this compound to MDA-MB231 cells also inhibited in vitro invasion. These studies suggest that plasma membrane V-ATPases play an important role in invasion of breast cancer cells.

  10. Understanding a Breast Cancer Diagnosis

    Science.gov (United States)

    ... Cancer A-Z Breast Cancer Understanding a Breast Cancer Diagnosis If you’ve been diagnosed with breast cancer, ... Prevention Early Detection and Diagnosis Understanding a Breast Cancer Diagnosis Treatment Breast Reconstruction Surgery Living as a Breast ...

  11. 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

  12. Src and CXCR4 are involved in the invasiveness of breast cancer cells with acquired resistance to lapatinib.

    Science.gov (United States)

    De Luca, Antonella; D'Alessio, Amelia; Gallo, Marianna; Maiello, Monica R; Bode, Ann M; Normanno, Nicola

    2014-01-01

    Lapatinib is a dual EGFR and ErbB-2 tyrosine kinase inhibitor that has significantly improved the clinical outcome of ErbB-2-overexpressing breast cancer patients. However, patients inexorably develop mechanisms of resistance that limit the efficacy of the drug. In order to identify potential targets for therapeutic intervention in lapatinib-resistant patients, we isolated, from ErbB-2-overexpressing SK-Br-3 breast cancer cells, the SK-Br-3 Lap-R-resistant subclone, which is able to routinely grow in 1 µM lapatinib. Resistant cells have a more aggressive phenotype compared with parental cells, as they show a higher ability to invade through a matrigel-coated membrane. Lapatinib-resistant cells have an increased Src kinase activity and persistent levels of activation of ERK1/2 and AKT compared with parental cells. Treatment with the Src inhibitor saracatinib in combination with lapatinib reduces AKT and ERK1/2 phosphorylation and restores the sensitivity of resistant cells to lapatinib. SK-Br-3 Lap-R cells also show levels of expression of CXCR4 that are higher compared with parental cells and are not affected by Src inhibition. Treatment with saracatinib or a specific CXCR4 antibody reduces the invasive ability of SK-Br-3 Lap-R cells, with the two drugs showing cooperative effects. Finally, blockade of Src signaling significantly increases TRAIL-induced cell death in SK-Br-3 Lap-R cells. Taken together, our results demonstrate that breast cancer cells with acquired resistance to lapatinib have a more aggressive phenotype compared with their parental counterpart, and that Src signaling and CXCR4 play an important role in this phenomenon, thus representing potential targets for therapeutic intervention in lapatinib-resistant breast cancer patients.

  13. Role of Wnt Co-receptor LRP6 in Triple Negative Breast Cancer Cell Migration and Invasion.

    Science.gov (United States)

    Ma, Jinlu; Lu, Wenyan; Chen, Dongquan; Xu, Bo; Li, Yonghe

    2017-03-01

    The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential Wnt co-receptor of the Wnt/β-catenin signaling pathway. Although studies have shown an increased expression of LRP6 in several types of cancer, its function in tumor development and progression remains to be elucidated. We herein demonstrated that LRP6 expression is up-regulated in human triple negative breast cancer (TNBC) patients and human TNBC cell lines, and that knockdown of LRP6 expression and treatment of recombinant Mesd protein (a specific inhibitor of LRP6) significantly decreased cell migration and invasion of TNBC MDA-MB-231 and BT549 cells. Interestingly, the effects of LRP6 knockdown and Mesd treatment on TNBC cell migration and invasion were more prominent than on TNBC cell proliferation/viability. Mechanistically, LRP6 knockdown and Mesd treatment inhibited Wnt/β-catenin signaling and decreased the expression of S100A4, a mediator of cancer metastasis and a specific target of Wnt/β-catenin signaling, in TNBC cells. Together, our data suggest that LRP6 promotes TNBC cell migration and invasion by regulating the expression and function of S100A4 via the Wnt/β-catenin signaling pathway. This article is protected by copyright. All rights reserved.

  14. 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.

  15. 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.

  16. Breast Cancer Treatment

    Science.gov (United States)

    ... Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  17. METCAM/MUC18 augments migration, invasion, and tumorigenicity of human breast cancer SK-BR-3 cells.

    Science.gov (United States)

    Zeng, Guofang; Cai, Shaoxi; Liu, Yuan; Wu, Guang-Jer

    2012-01-15

    Previous research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as a promoter or a suppressor in the development of human breast cancer by MCF7, MDA-MB-231, and MDA-MB-468. To resolve these conflicting results we have investigated the role of this CAM in the progression of the three aforementioned cell lines plus one additional human breast cancer cell line, SK-BR-3. We transfected the SK-BR-3 cells with human METCAM/MUC18 cDNA to obtain G418-resistant clones, which expressed different levels of the protein and which were used to test the effect of human METCAM/MUC18 expression on in vitro motility, invasiveness, anchorage-independent colony formation in soft agar, disorganized growth in a 3D basement membrane culture assay, and in vivo tumorigenesis in athymic nude mice. Enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, and anchorage-independent colony formation of SK-BR-3 cells and favored disorganized growth of the cells in 3D basement membrane culture. Enforced expression also increased tumorigenicity and final tumor weights of SK-BR-3 clones/cells after subcutaneous injection of the cells under the left third nipple of female athymic nude mice. To understand the mechanisms, we also determined the expression of several downstream key effectors in the tumors. Tumor cells from METCAM/MUC18 expressing clones exhibited elevated expression of an anti-apoptotic and survival index (Bcl2), an aerobic glycolysis index (LDH-A), and pro-angiogenesis indexes (VEGF and VAGFR2). We concluded that human METCAM/MUC18 promotes the development of breast cancer cells by increasing an anti-apoptosis and survival pathway and augmenting aerobic glycolysis and angiogenesis.

  18. 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.

  19. 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

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

    Science.gov (United States)

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

    2010-07-19

    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.

  1. What Is Breast Cancer in Men?

    Science.gov (United States)

    ... of the breast are glandular tissue (they make breast milk in women), so cancers starting in these areas are sometimes called adenocarcinomas. ... invasive) lobular carcinoma (ILC) This type of breast cancer starts in ... that, in women, produce breast milk) and grows into the fatty tissue of the ...

  2. A regulatory loop involving miR-22, Sp1, and c-Myc modulates CD147 expression in breast cancer invasion and metastasis.

    Science.gov (United States)

    Kong, Ling-Min; Liao, Cheng-Gong; Zhang, Yang; Xu, Jing; Li, Yu; Huang, Wan; Zhang, Yi; Bian, Huijie; Chen, Zhi-Nan

    2014-07-15

    Breast cancer is the most common cancer in women for which the metastatic process is still poorly understood. CD147 is upregulated in breast cancer and has been associated with tumor progression, but little is known about its regulatory mechanisms. In this study, we demonstrated that CD147 was overexpressed in breast cancer tissues and cell lines, and the high expression correlated with tumor invasion and metastasis. We also found that the transcription factors Sp1 and c-Myc could bind to the CD147 promoter and enhance its expression. The CD147 mRNA has a 748-bp 3'-untranslated region (UTR) with many miRNA target sites, suggesting possible regulation by miRNAs. We discovered that miR-22 repressed CD147 expression by directly targeting the CD147 3'UTR. We also determined that miR-22 could indirectly participate in CD147 modulation by downregulating Sp1 expression. miR-22 could form an autoregulatory loop with Sp1, which repressed miR-22 transcription by binding to the miR-22 promoter. Together with the c-Myc-mediated inhibition of miR-22 expression, our investigation identified a miR-22/Sp1/c-Myc network that regulates CD147 gene transcription. In addition, miR-22 overexpression suppressed breast cancer cell invasion, metastasis, and proliferation by targeting CD147 in vitro and in vivo. Furthermore, we found that miR-22 was significantly downregulated in breast cancer tissues and that its expression was inversely correlated with the tumor-node-metastasis stage and lymphatic metastasis in patients. Our study provides the first evidence that an miR-22/Sp1/c-Myc network regulates CD147 upregulation in breast cancer and that miR-22 represses breast cancer invasive and metastatic capacities.

  3. Enhanced invasion and tumor growth of fibroblast growth factor 8b-overexpressing MCF-7 human breast cancer cells.

    Science.gov (United States)

    Ruohola, J K; Viitanen, T P; Valve, E M; Seppänen, J A; Loponen, N T; Keskitalo, J J; Lakkakorpi, P T; Härkönen, P L

    2001-05-15

    Fibroblast growth factor 8 (FGF-8) is a secreted heparin-binding protein, which has mitogenic and transforming activity. Increased expression of FGF-8 has been found in human breast cancer, and it has a potential autocrine role in its progression. Human FGF-8 is alternatively spliced to generate four protein isoforms (a, b, e, and f). Isoform b has been shown to be the most transforming. In this work, we studied the role of FGF-8b in the growth (in vitro and in vivo) of MCF-7 human breast cancer cells, which proliferate in an estrogen-dependent manner. Constitutive overexpression of FGF-8b in MCF-7 cells down-regulated FGF-8b-binding receptors FGF receptor (FGFR) 1IIIc, FGFR2IIIc, and FGFR4 found to be expressed in these cells. FGF-8b overexpression led to an increase in the anchorage-independent proliferation rate in suspension culture and colony formation in soft agar, when MCF-7 cells were cultured with or without estradiol. FGF-8b also provided an additional growth advantage for cells stimulated with estradiol. In addition, FGF-8b-transfected cells invaded more actively through Matrigel than did control cells. This was possibly due to the increased secretion of matrix metalloproteinase 9. In vivo, FGF-8b-transfected MCF-7 cells formed faster growing tumors than vector-only-transfected cells when xenografted into nude mice. The tumors formed by FGF-8b-transfected cells were more vascular than the tumors formed by vector-only-transfected cells. In conclusion, FGF-8b expression confers a growth advantage to MCF-7 breast carcinoma cells, both in vitro and in vivo. In addition to stimulation of proliferation, this growth advantage probably arises from increased invasion and tumor vascularization induced by FGF-8b. The results suggest that FGF-8b signaling may be an important factor in the regulation of tumorigenesis and progression of human breast cancer.

  4. Comparison of multiplex ligation dependent probe amplification to immunohistochemistry for assessing HER-2/neu amplification in invasive breast cancer.

    Science.gov (United States)

    Purnomosari, D; Aryandono, T; Setiaji, K; Nugraha, S B; Pals, G; van Diest, P J

    2006-01-01

    The HER-2/neu transmembrane tyrosine kinase receptor is both a prognostic marker and a therapeutic target for breast cancer. Accurate determination of HER-2/neu status is a prerequisite for selecting breast tumors for HER-2/neu immunotherapy or for taxan based chemotherapy. Unfortunately, there is no consensus concerning how this determination should be reached. We compared assessment of HER-2/neu status using Multiplex ligation-dependent probe amplification (MLPA) and immunohistochemistry (IHC). The patient group comprised 60 Indonesian breast cancers patients. IHC was performed on paraffin sections using the CB11 antibody from Novocastra. Results were scored according to the Hercept test. For MLPA, DNA was extracted from frozen samples, PCR amplified with a probe set containing three hemi-primer sets for the HER-2 locus and another nine control probes spread over chromosome 17 and other chromosomes, and analyzed on a gene scanner. A ratio above two for at least two HER-2 locus probes compared to the control probes was regarded as amplification. IHC for HER-2/neu was negative in 36 cases, and 24 cases (40%) showed expression. Seven, eight and nine of the latter cases were 1+, 2+ and 3+ positive, respectively. Forty-seven cases showed no amplification by MLPA, and 13 cases (22%) were amplified. Comparison of IHC and MPLA showed that none of the 36 IHC-negative or seven IHC 1+ cases was amplified. Five of the eight (63%) 2+ cases were amplified, and eight of nine (89%) of the IHC 3+ tumors showed gene amplification by MLPA assay. For HER-2/neu, there is a good correlation between gene amplification detected by MLPA and overexpression by IHC in invasive breast cancer. It appears that MLPA can detect the HER-2 amplified cases in the IHC 2+ class. Because MLPA is quick and inexpensive, it is an attractive method for detecting HER-2/neu amplification in daily laboratory practice.

  5. 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.

  6. Breast Cancer -- Male

    Science.gov (United States)

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

  7. 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

  8. Effects of Inhibiting JAK on Invasion and Metastasis of the Human Breast Cancer Cells through ERK Signaling Transduction Pathway

    Institute of Scientific and Technical Information of China (English)

    Jing Zhao; Hong-fang Chen; Hua-yu Deng

    2009-01-01

    Objective: To explore the effects of Janus activated kinase (JAK) inhibitor AG490 on the phosphorylation of extracellular signal regulated protein kinase (ERK) in human breast cancer cells MDA-MB-231 and the roles of JAK in the invasion and metastasis of the human breast cancer cells through ERK signaling transduction pathways.Methods: MDA-MB-231 cells were treated with 20 (mol/L, 40 (mol/L, 80 (mol/L Janus kinase inhibitor AG490 for 24, 48 and 72 h. Proliferation and adhesion of MDA-MB-231 cells to matrigel were measured with MTT assay. When treated with 40 (mol/L AG490 for 24 h, the expressions of P-ERK and MMP-9 of cells were detected by Western-blot and invasion and metastasis of MDA-MB-231 cells were evaluated with transwell chamber.Results: After being treated with 20 (mol/L, 40 (mol/L, 80 (mol/L AG490 for 24, 48 and 72 h, the proliferation of MDA-MB-231 cells was inhibited in a dose-and time-dependent manner. MDA-MB-231 cells treated with 40 (mol/L AG490 for 30, 60, 90 and 120 min resulted in the increasing adhesion of cells to Matrigel in a time-dependent manner. However, capacity of adhesion in the group treated with AG490 was significantly decreased in comparison with the control group (P<0.01). The expression level of P-ERK and MMP-9 were decreased when treated with AG490. After treatment with 40 (mol/L AG490, in invasion assay, the number of cells in AG490 treated group to migrate to filter coated with Matrigel was reduced compared with control group (P<0.05). Meanwhile, in migration assay, the number of cells in AG490 treated group to migrate to filter was also decreased compared with control group (P<0.05).Conclusion: Our study indicates that JAK kinase could affect the activity of ERK signal transduction pathway through the phosphorylation of ERK. The inhibitory effects of JAK kinase on MMP-9 expression and invasion of breast cancer cells were associated with the down-regulation of the ERK signaling pathway.

  9. 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

    , three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend ....01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast...... cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function....

  10. 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.

  11. Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers.

    Science.gov (United States)

    Mori, Taizo; Kariya, Yoshinobu; Komiya, Eriko; Higashi, Shouichi; Miyagi, Yohei; Sekiguchi, Kiyotoshi; Miyazaki, Kaoru

    2011-05-01

    Laminins present in the basement membranes (BM) of blood vessels are involved in angiogenesis and other vascular functions that are critical for tumor growth and metastasis. Two major vascular laminins, the α4 (laminin-411/421) and α5 (laminin-511/521) types, have been well characterized. We recently found a third type of vascular laminin, laminin-3B11, consisting of the α3B, β1 and γ1 chains, and revealed its biological activity. Laminin-3B11 potently stimulates vascular endothelial cells to extend lamellipodial protrusions. To understand the roles of laminin-3B11 in blood vessel functions and tumor growth, we examined localization of the laminin α3B chain in normal mammary glands and breast cancers, in comparison with the α4 and α5 laminins. In the immunohistochemical analysis, the α3B laminin was co-localized with the α4 and α5 laminins in the BM of venules and capillaries of normal breast tissues, but α3B was scarcely detected in vessels near invasive breast carcinoma cells. In contrast, the α4 laminin was overexpressed in capillaries of invasive carcinomas, where a large number of macrophages were found. The α5 laminin appeared to be weakly downregulated in cancer tissues, especially in capillary vessels. Furthermore, our in vitro analysis indicated that TNF-α significantly suppressed the laminin α3B expression in vascular endothelial cells, while it, as well as IL-1β and TGF-α, upregulated the α4 expression. These results suggest that Lm3B11/3B21 may be required for normal mature vessels and interfere with tumor angiogenesis.

  12. The value of breast MRI in high‐risk patients with newly diagnosed breast cancer to exclude invasive disease in the contralateral prophylactic mastectomy: Is there a role to choose wisely patients for sentinel node biopsy?

    OpenAIRE

    Freitas, Vivianne; Crystal, Pavel; Kulkarni, Supriya R.; Ghai, Sandeep; Bukhanov, Karina; Escallon, Jaime; Scaranelo, Anabel M.

    2016-01-01

    Abstract The aim of this study was to evaluate the presence of clinically and mammographically occult disease using breast MRI in a cohort of cancer patients undergoing contralateral prophylactic mastectomy (CPM) and the utmost indication of axillary assessment (sentinel node biopsy (SLNB)) for this side. A retrospective review of patients with unilateral invasive breast cancer or ductal carcinoma in situ (DCIS) from institutional MRI registry data (2004–2010) was conducted. Characteristics o...

  13. 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.

  14. 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

  15. Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study

    Science.gov (United States)

    Duffy, Stephen W; Dibden, Amanda; Michalopoulos, Dimitrios; Offman, Judith; Parmar, Dharmishta; Jenkins, Jacquie; Collins, Beverley; Robson, Tony; Scorfield, Suzanne; Green, Kathryn; Hall, Clare; Liao, Xiao-Hui; Ryan, Michael; Johnson, Fiona; Stevens, Guy; Kearins, Olive; Sellars, Sarah; Patnick, Julietta

    2016-01-01

    Summary Background The value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen. Methods We obtained aggregate data for screen-detected cancers from 84 local screening units within 11 regional Quality Assurance Reference Centres in England, Wales, and Northern Ireland from the National Health Service Breast Screening Programme. Data for DCIS diagnoses were obtained for women aged 50–64 years who were invited to and attended mammographic breast screening from April 1, 2003, to March 31, 2007 (4 screening years). Patient-level data for interval cancer arising in the 36 months after each of these were analysed by Poisson regression with invasive interval cancer screen detection rate as the outcome variable; DCIS detection frequencies were fitted first as a continuous and then as a categorical variable. We repeated this analysis after adjustment with both small size and high-grade invasive screen-detected cancers. Findings We analysed data for 5 243 658 women and on interval cancers occurring in the 36 months after the relevant screen. The average frequency of DCIS detected at screening was 1·60 per 1000 women screened (median 1·50 [unit range 1·54–3·56] per 1000 women). There was a significant negative association of screen-detected DCIS cases with the rate of invasive interval cancers (Poisson regression coefficient −0·084 [95% CI −0·13 to −0·03]; p=0·002). 90% of units had a DCIS detection frequency within the range of 1·00 to 2·22 per 1000 women; in these units, for every three screen-detected cases of DCIS, there was one fewer invasive interval cancer in the next 3 years. This association remained after

  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...... network that is crucial for invasion in vitro, and defines a specific role and targets for the identified serine-threonine kinases....

  17. 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

  18. 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.

  19. Male Breast Cancer

    Science.gov (United States)

    ... breast cancer include exposure to radiation, a family history of breast cancer, and having high estrogen levels, which can happen with diseases like cirrhosis or Klinefelter's syndrome. Treatment for male breast cancer is usually ...

  20. 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.

  1. 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.

  2. Morphologic complexity of epithelial architecture for predicting invasive breast cancer survival

    Directory of Open Access Journals (Sweden)

    Tambasco Mauro

    2010-12-01

    Full Text Available Abstract Background Precise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry (pathological grade. There is a need to replace subjective criteria with objective measurements to improve risk assessment and therapeutic decisions. We assessed the prognostic value of fractal dimension (an objective measure of morphologic complexity for invasive ductal carcinoma of the breast. Methods We applied fractal analysis to pan-cytokeratin stained tissue microarray (TMA cores derived from 379 patients. Patients were categorized according to low (1.75, N = 90 fractal dimension. Cox proportional-hazards regression was used to assess the relationship between disease-specific and overall survival and fractal dimension, tumour size, grade, nodal status, estrogen receptor status, and HER-2/neu status. Results Patients with higher fractal score had significantly lower disease-specific 10-year survival (25.0%, 56.4%, and 69.4% for high, intermediate, and low fractal dimension, respectively, p Conclusion Except for nodal status, morphologic complexity of breast epithelium as measured quantitatively by fractal dimension was more strongly and significantly associated with disease-specific and overall survival than standard prognosticators.

  3. Breast cancer in pregnancy.

    Science.gov (United States)

    Krishna, Iris; Lindsay, Michael

    2013-09-01

    Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy or in the first postpartum year. Breast cancer is one of the more common malignancies to occur during pregnancy and, as more women delay childbearing, the incidence of breast cancer in pregnancy is expected to increase. This article provides an overview of diagnosis, staging, and treatment of pregnancy-associated breast cancer. Recommendations for management of breast cancer in pregnancy are discussed.

  4. P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells.

    Science.gov (United States)

    Eun, So Young; Ko, Young Shin; Park, Sang Won; Chang, Ki Churl; Kim, Hye Jung

    2015-07-01

    Tumor metastasis is considered the main cause of mortality in cancer patients, thus it is important to investigate the differences between high- and low-metastatic cancer cells. Our previous study showed that the highly metastatic breast cancer cell line MDA-MB-231 released higher levels of ATP and exhibited higher P2Y2R activity compared with the low-metastatic breast cancer cell line MCF-7. In addition, P2Y2R activation by ATP released from MDA-MB-231 cells induced hypoxia-inducible factor-1α expression, lysyl oxidase secretion and collagen crosslinking, generating a receptive microenvironment for pre-metastatic niche formation. Thus, in the present study, we investigated which P2Y2R-related signaling pathways are involved in the invasion of breast cancer cells. The highly metastatic breast cancer cells MDA-MB-231 and SK-BR-3 showed higher invasion than MCF-7 and T47D cells at a basal level, which was abolished through P2Y2R knockdown or in the presence of apyrase, an enzyme that hydrolyzes extracellular nucleotides. MDA-MB-231 cells also showed high levels of mesenchymal markers, such as Snail, Vimentin and N-cadherin, but not the epithelial marker E-cadherin and this expression was inhibited through ATP degradation or P2Y2R knockdown. Moreover, SK-BR-3 and MDA-MB231 cells exhibited higher ERK and PKC phosphorylation levels than T47D and MCF-7 cells and upregulated phospho-ERK and -PKC levels in MDA-MB-231 cells were significantly downregulated by apyrase or P2Y2R knockdown. Specific inhibitors of ERK, PKC and PLC markedly reduced the invasion and levels of mesenchymal marker expression in MDA-MB-231 cells. These results suggest that over-activated ERK and PKC pathways are involved in the P2Y2R-mediated invasion of breast cancer cells.

  5. 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.

  6. 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

  7. 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

  8. miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN

    Science.gov (United States)

    Fang, Hong; Xie, Jiping; Zhang, Min; Zhao, Ziwei; Wan, Yi; Yao, Yongqiang

    2017-01-01

    MicroRNAs (miRNAs) are small single-stranded RNAs that bind to the 3’UTR of the mRNAs of target genes. They can target multiple genes and regulate translation or degradation of the mRNA. miRNAs target genes in a tissue-specific manner, and the role of a particular miRNA varies according to tumor origin or even subtype within the same cancer. This study evaluated the effect of miR-21 expression in triple-negative breast cancer (TNBC) tissues and MDA-MB-468, a cell line derived from TNBC tissues. miR-21 was consistently upregulated in TNBC and MDA-MB-468 cells compared to normal tissues. Inhibition of miR-21 by miR-21 antisense oligonucleotides decreased the proliferation, viability, and invasiveness of MDA-MB-468 cells and enhanced apoptosis. Furthermore, we confirmed that PTEN was downregulated by miR-21 in MDA-MB-468 cells. The results indicated that PTEN may mediate the oncogenic properties of miR-21 in TNBC. In summary, miR-21 was upregulated in TNBC tissues and cells, and promoted the proliferation and invasion of MDA-MB-468 cells, but negatively regulated the expression of PTEN protein. Inhibition of miR-21 or overexpression of PTEN protein could be promising strategies for the treatment of patients with TNBC.

  9. 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.

  10. Glut1 promotes cell proliferation, migration and invasion by regulating epidermal growth factor receptor and integrin signaling in triple-negative breast cancer cells.

    Science.gov (United States)

    Oh, Sunhwa; Kim, Hyungjoo; Nam, KeeSoo; Shin, Incheol

    2017-03-01

    Elevated glucose levels in cancer cells can be attributed to increased levels of glucose transporter (GLUT) proteins. Glut1 expression is increased in human malignant cells. To investigate alternative roles of Glut1 in breast cancer, we silenced Glut1 in triple-negative breast-cancer cell lines using a short hairpin RNA (shRNA) system. Glut1 silencing was verified by Western blotting and qRT-PCR. Knockdown of Glut1 resulted in decreased cell proliferation, glucose uptake, migration, and invasion through modulation of the EGFR/ MAPK signaling pathway and integrin β1/Src/FAK signaling pathways. These results suggest that Glut1 not only plays a role as a glucose transporter, but also acts as a regulator of signaling cascades in the tumorigenesis of breast cancer. [BMB Reports 2017; 50(3): 132-137].

  11. [Occult multicentric breast cancer].

    Science.gov (United States)

    Vtorushin, S V; Zab'ialova, M V; Glushchenko, S A; Perel'muter, V M; Slonimskaia, E M

    2009-01-01

    The study included 92 patients with invasive ductal breast cancer (T2-4N0-2M0-1). In 38 cases, tumor growth was unicentric while histologically identifiable ones as multicentric in 44. Multicentricity mostly occurred in cases of macroscopically-identifiable nodes located in the central segments of the breast. Clinically-identifiable nodes of multicentric tumor growth measured more than 3 cm. Multicentric tumors were mostly grade III, featured lower expression of sex hormone receptors and positive Her2 status.

  12. Effects of Neuregulins on Invasion and Metastasis of Non-overexpression ErbB2 Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Ya-mei Zhang; Ting-ting Zhao; Hua-yu Deng

    2009-01-01

    Objective: To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods: The expressions of neuregulin were detected by immunocytochemistry and Western blot. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferations were measured with MTT assay. Invasion and metastasis of MDA-ME-231 cells were evaluated with transwell chamber. The enzyme activities of MMP-2 and MMP-9 were detected by gelatin zymography. The expressions of MMP-2 and HIF-1α were detected by Western blot.Results: MDA-MB-231 cells expressed a relatively higher level of neuregulin. In Western blot, the positive reaction band was found at 44KD which coincides with the molecular weight of NRG. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in a time-dose-dependent manner (P<0.01), invasion and metastasis were also depressed (P<0.05). The enzyme activities of MMP-2 and MMP-9 were lower (P<0.05). The expression levels of MMP-2 and HIF-1α were decreased (P<0.05).Conclusion: Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins, neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine secretion, and induce invasion and metastasis of MDA-MB-231 cells.

  13. 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.

  14. Breast Cancer Disparities

    Science.gov (United States)

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

  15. Breast cancer in men

    Science.gov (United States)

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

  16. 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

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

    Science.gov (United States)

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

    2017-04-01

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

  18. 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.

  19. 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.

  20. 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...

  1. 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.

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

    Science.gov (United States)

    Zhang, Fei; Wang, Zhiyong; Fan, Yanling; Xu, Qiao; Ji, Wei; Tian, Ran; Niu, Ruifang

    2015-10-16

    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.

  3. 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.

  4. [CD147 expression in non-invasive and invasive breast carcinoma].

    Science.gov (United States)

    Nagashima, Saki; Sakurai, Kenichi; Suzuki, Shuhei; Hara, Yukiko; Maeda, Tetsuyo; Hirano, Tomohisa; Enomoto, Katsuhisa; Amano, Sadao; Koshinaga, Tsugumichi

    2014-10-01

    CD147 is a multifunctional membrane glycoprotein involved in tumor invasion, and is overexpressed in many solid tumors. However, the role of CD147 in breast cancer is not well understood. The aim of this study was to evaluate CD147 expression in non-invasive and invasive ductal carcinomas. We recruited 156 breast cancer patients who underwent radical operations at our hospital up until 2002. We performed immunohistochemistry on their tumor specimens, and compared these data with clinicopathological factors. We divided the patients into two groups: group A was comprised of non-invasive ductal carcinomas and group B, invasive ductal carcinomas. The CD147-positive rate was 62.8% for all patients and was higher in group B than group A. In all cases, the CD147-positive rate correlated with clinical stage, number of metastatic lymph nodes, and tumor size. These results implied that CD147 may be involved in the process of breast cancer invasion.

  5. Taiwan cobra cardiotoxin III suppresses EGF/EGFR-mediated epithelial-to-mesenchymal transition and invasion of human breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Tsai, Pei-Chien; Fu, Yaw-Syan; Chang, Long-Sen; Lin, Shinne-Ren

    2016-03-01

    Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. The epithelial-to-mesenchymal transition (EMT) has emerged as a pivotal event in the development of the invasive and metastatic potentials of cancer progression. Epidermal growth factor (EGF) and its receptor, EGFR, play roles in cancer metastasis. CTX III, a basic polypeptide isolated from Naja naja atra venom, has been shown to exhibit anticancer activity; however, the effect of CTX III on the EMT of cancer cells remains elusive. CTX III treatment resulted in morphological changes from elongated and spindle shape to rounded and epithelial-like shape, induced upregulation of E-cadherin and concurrent downregulation of N-cadherin and Vimentin protein levels, corresponding to observed decreases in cell migration and invasion. CTX III treatment also decreased the expression of Snail and Twist in EGF-induced MDA-MB-231 cells. Concurrently, CTX III efficiently inhibited the EGFR phosphorylation and downstream activation of phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2. The EGFR specific inhibitor AG1478 significantly suppressed ERK1/2 and Akt phosphorylation, cell migration and invasion, as well as the expressional changes associated with EMT markers in EGF-induced MDA-MB-231 cells. CTX III inhibitory effect on EGF-evoked invasion of MDA-MB-231 cells is mediated through suppressing EGF/EGFR activation and EMT process.

  6. 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.

  7. 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.

  8. Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients.

    Science.gov (United States)

    Sa-Nguanraksa, Doonyapat; Suntiparpluacha, Monthira; Kulprom, Anchalee; Kummalue, Tanawan; Chuangsuwanich, Tuenjai; Avirutnan, Panissadee; O-Charoenrat, Pornchai

    2016-01-01

    Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

  9. IGF-1 increases invasive potential of MCF 7 breast cancer cells and induces activation of latent TGF-β1 resulting in epithelial to mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Damjanovski Sashko

    2011-05-01

    Full Text Available Abstract Introduction TGF-β signaling has been extensively studied in many developmental contexts, amongst which is its ability to induce epithelial to mesenchymal transitions (EMT. EMTs play crucial roles during embryonic development and have also come under intense scrutiny as a mechanism through which breast cancers progress to become metastatic. Interestingly, while the molecular hallmarks of EMT progression (loss of cell adhesion, nuclear localization of β-catenin are straightforward, the cellular signaling cascades that result in an EMT are numerous and diverse. Furthermore, most studies describing the biological effects of TGF-β have been performed using high concentrations of active, soluble TGF-β, despite the fact that TGF-β is produced and secreted as a latent complex. Methods MCF-7 breast cancer cells treated with recombinant IGF-1 were assayed for metalloproteinase activity and invasiveness through a matrigel coated transwell invasion chamber. IGF-1 treatments were then followed by the addition of latent-TGF-β1 to determine if elevated levels of IGF-1 together with latent-TGF-β1 could cause EMT. Results Results showed that IGF-1 - a molecule known to be elevated in breast cancer is a regulator of matrix metalloproteinase activity (MMP and the invasive potential of MCF-7 breast cancer cells. The effects of IGF-1 appear to be mediated through signals transduced via the PI3K and MAPK pathways. In addition, increased IGF-1, together with latent TGF-β1 and active MMPs result in EMT. Conclusions Taken together our data suggest a novel a link between IGF-1 levels, MMP activity, TGF-β signaling, and EMT in breast cancer cells.

  10. 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.

  11. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

    Science.gov (United States)

    Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

    2017-03-01

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

  12. The lipid peroxidation in breast cancer patients.

    Science.gov (United States)

    Kedzierska, Magdalena; Olas, Beata; Wachowicz, Barbara; Jeziorski, Arkadiusz; Piekarski, Janusz

    2010-06-01

    The aim of our study was to estimate oxidative stress (by using different biomarkers of lipid peroxidation--isoprostanes and thiobarbituric acid reactive substances (TBARS)) in patients with invasive breast cancer, patients with benign breast diseases and in a control group. We observed a statistically increased level of TBARS in plasma and isoprostanes in urine of patients with invasive breast cancer in comparison with a control group. The concentration of tested biomarkers in plasma or urine from patients with invasive breast cancer was also higher than in patients with benign breast diseases. Moreover, the levels of tested markers in patients with benign breast diseases and in a control group did not differ. Considering the data presented in this study, we suggest that free radicals induce peroxidation of unsaturated fatty acid in patients with breast cancer.

  13. Rac1 and Stathmin but Not EB1 Are Required for Invasion of Breast Cancer Cells in Response to IGF-I

    Directory of Open Access Journals (Sweden)

    Shigeru Morimura

    2011-01-01

    Full Text Available Cell migration is considered necessary for the invasion that accompanies the directional formation of the cellular protrusions termed lamellipodia. In invasive breast cancer MDA-MB-231 cells, lamellipodia formation is preceded by translocation of the actin cytoskeletal regulatory protein WAVE2 to the leading edge. WAVE2 translocation and lamellipodia formation require many signaling molecules, including PI3K, Rac1, Pak1, IRSp53, stathmin, and EB1, but whether these molecules are necessary for invasion remains unclear. In noninvasive breast cancer MCF7 cells, no lamellipodia were induced by IGF-I, whereas in MDA-MB-231 cells, Rac1, stathmin, and EB1 were overexpressed. Depletion of Rac1 or stathmin by small interfering RNA abrogated the IGF-I-induced invasion of MDA-MB-231 cells; however, depletion of EB1 did not, indicating the necessity of Rac1 and stathmin but not EB1 for invasion. The signaling pathway leading to cell invasion may not be identical but shares some common molecules, leading to cell migration through lamellipodia formation.

  14. 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

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Uchino Masahiro

    2010-08-01

    Full Text Available Abstract Background 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? Methods 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. Results 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

  18. Male Breast Cancer

    Science.gov (United States)

    ... ducts that carry milk to the nipples, and fat. During puberty, women begin developing more breast tissue, and men do not. But because men are born with a small amount of breast tissue, they can develop breast cancer. Types of breast cancer diagnosed in men include: Cancer ...

  19. The value of breast MRI in high-risk patients with newly diagnosed breast cancer to exclude invasive disease in the contralateral prophylactic mastectomy: Is there a role to choose wisely patients for sentinel node biopsy?

    Science.gov (United States)

    Freitas, Vivianne; Crystal, Pavel; Kulkarni, Supriya R; Ghai, Sandeep; Bukhanov, Karina; Escallon, Jaime; Scaranelo, Anabel M

    2016-06-01

    The aim of this study was to evaluate the presence of clinically and mammographically occult disease using breast MRI in a cohort of cancer patients undergoing contralateral prophylactic mastectomy (CPM) and the utmost indication of axillary assessment (sentinel node biopsy (SLNB)) for this side. A retrospective review of patients with unilateral invasive breast cancer or ductal carcinoma in situ (DCIS) from institutional MRI registry data (2004-2010) was conducted. Characteristics of patients undergoing CPM with breast MRI obtained less than 6 month before surgery were evaluated. A total of 2322 consecutive patients diagnosed with DCIS or stage I to III infiltrating breast cancer underwent preoperative breast MRI. Of these, 1376 patients (59.2%) had contralateral clinical breast exam and mammography without abnormalities; and 116 patients (4.9%) underwent CPM (28 excluded patients had breast MRI more than 6 months before CPM). The mean age of the 88 patients was 49 years (range 28-76 years). Two (2.3%) DCIS identified on surgical pathology specimen were not depicted by MRI and the 5 mm T1N0 invasive cancer (1.1%) was identified on MRI. Preoperative MRI showed 95% accuracy to demonstrate absence of occult disease with negative predicted value (NPV) of 98% (95% CI: 91.64-99.64%). Occult disease was present in 3.4% of CPM. MRI accurately identified the case of invasive cancer in this cohort. The high negative predictive value suggests that MRI can be used to select patients without consideration of SLNB for the contralateral side.

  20. Interstitial guidance of cancer invasion.

    Science.gov (United States)

    Gritsenko, Pavlo G; Ilina, Olga; Friedl, Peter

    2012-01-01

    Cancer cell invasion into healthy tissues develops preferentially along pre-existing tracks of least resistance, followed by secondary tissue remodelling and destruction. The tissue scaffolds supporting or preventing guidance of invasion vary in structure and molecular composition between organs. In the brain, the guidance is provided by myelinated axons, astrocyte processes, and blood vessels which are used as invasion routes by glioma cells. In the human breast, containing interstitial collagen-rich connective tissue, disseminating breast cancer cells preferentially invade along bundled collagen fibrils and the surface of adipocytes. In both invasion types, physical guidance prompted by interfaces and space is complemented by molecular guidance. Generic mechanisms shared by most, if not all, tissues include (i) guidance by integrins towards fibrillar interstitial collagen and/or laminins and type IV collagen in basement membranes decorating vessels and adipocytes, and, likely, CD44 engaging with hyaluronan; (ii) haptotactic guidance by chemokines and growth factors; and likely (iii) physical pushing mechanisms. Tissue-specific, resticted guidance cues include ECM proteins with restricted expression (tenascins, lecticans), cell-cell interfaces, and newly secreted matrix molecules decorating ECM fibres (laminin-332, thrombospondin-1, osteopontin, periostin). We here review physical and molecular guidance mechanisms in interstitial tissue and brain parenchyma and explore shared principles and organ-specific differences, and their implications for experimental model design and therapeutic targeting of tumour cell invasion.

  1. 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.

  2. 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.

  3. MiR-487a Promotes TGF-β1-induced EMT, the Migration and Invasion of Breast Cancer Cells by Directly Targeting MAGI2.

    Science.gov (United States)

    Ma, Mengtao; He, Miao; Jiang, Qian; Yan, Yuanyuan; Guan, Shu; Zhang, Jing; Yu, Zhaojin; Chen, Qiuchen; Sun, Mingli; Yao, Weifan; Zhao, Haishan; Jin, Feng; Wei, Minjie

    2016-01-01

    Tumor metastasis is a complex and multistep process and its exact molecular mechanisms remain unclear. We attempted to find novel microRNAs (miRNAs) contributing to the migration and invasion of breast cancer cells. In this study, we found that the expression of miR-487a was higher in MDA-MB-231breast cancer cells with high metastasis ability than MCF-7 breast cancer cells with low metastasis ability and the treatment with transforming growth factor β1 (TGF-β1) significantly increased the expression of miR-487a in MCF-7 and MDA-MB-231 breast cancer cells. Subsequently, we found that the transfection of miR-487a inhibitor significantly decreased the expression of vimentin, a mesenchymal marker, while increased the expression of E-cadherin, an epithelial marker, in both MCF-7 cells and MDA-MB-231 cells. Also, the inactivation of miR-487a inhibited the migration and invasion of breast cancer cells. Furthermore, our findings demonstrated that miR-487a directly targeted the MAGI2 involved in the stability of PTEN. The down-regulation of miR-487a increased the expression of p-PTEN and PTEN, and reduced the expression of p-AKT in both cell lines. In addition, the results showed that NF-kappaB (p65) significantly increased the miR-487a promoter activity and expression, and TGF-β1 induced the increased miR-487a promoter activity via p65 in MCF-7 cells and MDA-MB-231 cells. Moreover, we further confirmed the expression of miR-487a was positively correlated with the lymph nodes metastasis and negatively correlated with the expression of MAGI2 in human breast cancer tissues. Overall, our results suggested that miR-487a could promote the TGF-β1-induced EMT, the migration and invasion of breast cancer cells by directly targeting MAGI2.

  4. 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.

  5. Breast cancer awareness

    OpenAIRE

    2012-01-01

    The incidence of breast cancer is rising among women in many European countries, affecting up to 1 in 16 women and has become the most common cause of cancer in European women. In Malta breast cancer is the commonest oncological cause of death in females. In fact 5.2% of all deaths in females in 2010 was from breast cancer.

  6. 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

    controls using LNA-based quantitative real-time PCR (qRT-PCR). A signature of miRNAs was subsequently validated in an independent set of 111 serum samples from 60 patients with early-stage breast cancer and 51 healthy controls and further tested for reproducibility in 3 independent data sets from the GEO......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-matched healthy...

  7. 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...

  8. Long-term results of breast conserving surgery vs. mastectomy for early stage invasive breast cancer: 20-year follow-up of the Danish randomized DBCG-82TM protocol

    DEFF Research Database (Denmark)

    Blichert-Toft, M.; Nielsen, M.; During, M.;

    2008-01-01

    The main objective of the present study aims at comparing the long-term efficacy of breast conserving surgery (BCS) vs. mastectomy (M) based on a randomized design. The Danish Breast Cancer Cooperative Group (DBCG) conducted the trial (DBCG-82TM) from January 1983 to March 1989 recruiting 1154...... patients with invasive breast carcinoma. Follow-up time ended 1(st) May 2006 with a median follow-up time of 19.6 years (time span 17.1-23.3 years). Eligibility criteria included a one-sided, unifocal, primary operable breast carcinoma, patient age below 70 years, probability of satisfactory cosmetic......% of the complete series. 10-year recurrence free survival (RFS) and 20-year overall survival (OS) based on intent to treat did not reveal significant differences in outcome between breast conserving surgery vs. mastectomy, p=0.95 and p=0.10, respectively. Including the complete series comprising 1133 eligible...

  9. 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.

  10. Gain-of-function of mutant p53: mutant p53 enhances cancer progression by inhibiting KLF17 expression in invasive breast carcinoma cells.

    Science.gov (United States)

    Ali, Amjad; Shah, Abdus Saboor; Ahmad, Ayaz

    2014-11-01

    Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and epithelial-mesenchymal-transition (EMT). However, its expression is downregulated in metastatic breast cancer that contains p53 mutations. Here, we show that mutant-p53 plays a key role to suppress KLF17 and thereby enhances cancer progression, which defines novel gain-of-function (GOF) of mutant-p53. Mutant-p53 interacts with KLF17 and antagonizes KLF17 mediated EMT genes transcription. Depletion of KLF17 promotes cell viability, decreases apoptosis and induces drug resistance in metastatic breast cancer cells. KLF17 suppresses cell migration and invasion by decreasing CD44, PAI-1 and Cyclin-D1 expressions. Taken together, our results show that KLF17 is important for the suppression of metastasis and could be a potential therapeutic target during chemotherapy.

  11. Breast cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  12. The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression.

    Science.gov (United States)

    Shepherd, Jonathan H; Uray, Ivan P; Mazumdar, Abhijit; Tsimelzon, Anna; Savage, Michelle; Hilsenbeck, Susan G; Brown, Powel H

    2016-03-15

    Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer.

  13. Breast Cancer Early Detection and Diagnosis

    Science.gov (United States)

    ... En Español Category Cancer A-Z Breast Cancer Breast Cancer Early Detection and Diagnosis Breast cancer is sometimes ... cancer screening is so important. Learn more. Can Breast Cancer Be Found Early? Breast cancer is sometimes found ...

  14. Breast Cancer and Infertility

    OpenAIRE

    2015-01-01

    Breast cancer is the most common malignancy among women and may accompany infertility. The relationship between infertility treatment and breast cancer has not yet been proven. However, estrogen exposure is well known to cause breast cancer. Recent advances in treatment options have provided young patients with breast cancer a chance of being mother [Archives Medical Review Journal 2015; 24(3.000): 317-323

  15. 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 ...

  16. 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.

  17. 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.

  18. 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.

  19. Down-regulation of c9orf86 in human breast cancer cells inhibits cell proliferation, invasion and tumor growth and correlates with survival of breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Yang-Yang Li

    Full Text Available C9orf86 which is a novel subfamily within the Ras superfamily of GTPases, is overexpressed in the majority of primary breast tumors. Few functional studies have focused on the C9orf86 protein; therefore, in this study, we explored the role of C9orf86 in breast carcinogenesis. In our study, we found that silencing of C9orf86 by siRNA in MCF-7 and SK-BR-3 cells resulted in suppressed cell proliferation as well as in vitro cell invasion capabilities. Moreover, knockdown of C9orf86 inhibited tumor growth in nude mice. Cell cycle and apoptotic assays showed that the anti-proliferative effect of C9orf86-siRNA was mediated by arresting cells in the G1 phase and promoting apoptosis. In addition, we found that patients with high levels of C9orf86 expression showed a significant trend towards worse survival compared to patients with low C9orf86 expression (P = 0.002. These results provide evidence that C9orf86 represents a novel and clinically useful biomarker for BC patients and plays an important role during the progression of BC.

  20. Minimally Invasive Molecular Staging (MIMS) RT-PCR Breast Cancer Study

    Science.gov (United States)

    2007-03-31

    31-03-2007 Final Report 19990426 - 20061231 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Minimally Invasive Molecular Staging (MIMS) N00014-99-1-0784 RT...carcinoma micrometastases in axillary lymph nodes by means of reverse-transcriptase Polymerase chain reaction: comparison between mucl mRNA and keratin-19

  1. 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.

  2. Autocrine/Paracrine Human Growth Hormone-stimulated MicroRNA 96-182-183 Cluster Promotes Epithelial-Mesenchymal Transition and Invasion in Breast Cancer.

    Science.gov (United States)

    Zhang, Weijie; Qian, Pengxu; Zhang, Xiao; Zhang, Min; Wang, Hong; Wu, Mingming; Kong, Xiangjun; Tan, Sheng; Ding, Keshuo; Perry, Jo K; Wu, Zhengsheng; Cao, Yuan; Lobie, Peter E; Zhu, Tao

    2015-05-29

    Human growth hormone (hGH) plays critical roles in pubertal mammary gland growth, development, and sexual maturation. Accumulated studies have reported that autocrine/paracrine hGH is an orthotopically expressed oncoprotein that promotes normal mammary epithelial cell oncogenic transformation. Autocrine/paracrine hGH has also been reported to promote mammary epithelial cell epithelial-mesenchymal transition (EMT) and invasion. However, the underlying mechanism remains largely obscure. MicroRNAs (miRNAs) are reported to be involved in regulation of multiple cellular functions of cancer. To determine whether autocrine/paracrine hGH promotes EMT and invasion through modulation of miRNA expression, we performed microarray profiling using MCF-7 cells stably expressing wild type or a translation-deficient hGH gene and identified miR-96-182-183 as an autocrine/paracrine hGH-regulated miRNA cluster. Forced expression of miR-96-182-183 conferred on epithelioid MCF-7 cells a mesenchymal phenotype and promoted invasive behavior in vitro and dissemination in vivo. Moreover, we observed that miR-96-182-183 promoted EMT and invasion by directly and simultaneously suppressing BRMS1L (breast cancer metastasis suppressor 1-like) gene expression. miR-96 and miR-182 also targeted GHR, providing a potential negative feedback loop in the hGH-GHR signaling pathway. We further demonstrated that autocrine/paracrine hGH stimulated miR-96-182-183 expression and facilitated EMT and invasion via STAT3 and STAT5 signaling. Consistent with elevated expression of autocrine/paracrine hGH in metastatic breast cancer tissue, miR-96-182-183 expression was also remarkably enhanced. Hence, we delineate the roles of the miRNA-96-182-183 cluster and elucidate a novel hGH-GHR-STAT3/STAT5-miR-96-182-183-BRMS1L-ZEB1/E47-EMT/invasion axis, which provides further understanding of the mechanism of autocrine/paracrine hGH-stimulated EMT and invasion in breast cancer.

  3. 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...

  4. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

    Science.gov (United States)

    Harris, Lyndsay N.; McShane, Lisa M.; Andre, Fabrice; Collyar, Deborah E.; Gonzalez-Angulo, Ana M.; Hammond, Elizabeth H.; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Bast, Robert C.; Hayes, Daniel F.

    2016-01-01

    Purpose To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. Methods A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. Recommendations In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. PMID:26858339

  5. 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 ...

  6. Computer-aided Diagnosis-generated Kinetic Features of Breast Cancer at Preoperative MR Imaging: Association with Disease-free Survival of Patients with Primary Operable Invasive Breast Cancer.

    Science.gov (United States)

    Kim, Jin Joo; Kim, Jin You; Kang, Hyun Jung; Shin, Jong Ki; Kang, Taewoo; Lee, Seok Won; Bae, Young Tae

    2017-03-02

    Purpose To retrospectively investigate the relationship between the kinetic features of breast cancer assessed with computer-aided diagnosis (CAD) at preoperative magnetic resonance (MR) imaging and disease-free survival in patients with primary operable invasive breast cancer. Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. The authors identified 329 consecutive women (mean age, 52.9 years; age range, 32-88 years) with newly diagnosed invasive breast cancer who had undergone preoperative MR imaging and surgery between January 2012 and February 2013. All MR images were retrospectively reviewed by using a commercially available CAD system, and the following kinetic parameters were noted for each lesion: peak enhancement (highest pixel signal intensity in the first series obtained after administration of contrast material), angio-volume (total volume of the enhancing lesion), and delayed enhancement profiles (the proportions of washout, plateau, and persistently enhancing component within a tumor). Cox proportional hazards modeling was used to identify the relationship between CAD-generated kinetics and disease-free survival after adjusting for clinical-pathologic variables. Results A total of 36 recurrences developed at a median follow-up of 50 months (range, 15-55 months). CAD-measured peak enhancement at preoperative MR imaging enabled differentiation between patients with and patients without recurrence (area under the receiver operating characteristic curve = 0.728; 95% confidence interval [CI]: 0.676, 0.775; P < .001). Multivariate Cox analysis showed that a higher peak enhancement (hazard ratio [HR] = 1.001; 95% CI: 1.000, 1.002; P = .004), a higher washout component (HR = 1.029; 95% CI: 1.005, 1.054; P = .017), and lymphovascular invasion at histopathologic examination (HR = 3.011; 95% CI: 1.302, 6.962; P = .010) were associated with poorer disease

  7. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... have revolutionized breast cancer treatment: tamoxifen (Nolvadex) and trastuzumab (Herceptin). Bernard Fisher, M.D., of the University of ... breast tumors. Dr. Slamon and his colleagues developed trastuzumab (Herceptin). Trastuzumab, a monoclonal antibody, was the first ...

  8. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    Science.gov (United States)

    2007-05-01

    Franko, A.; Koch, C.; Boisvert, D. Cancer Res. 1992, 52, 3831. [239] Ballinger , J.R. Semin. Nucl. Med. 2001, 31, 321. [240] Hodgkiss, R.J. Anti-cancer Drug...Tull, D.; Johns , K.; Withers, S. G.; Rose, D. R. Crystallographic observation of a covalent catalytic intermediate in a â-glycosidase. Nat. Struct...inclusion of fluorine atoms in libraries of ligands has been used to probe molecular interactions based on changes in line width and chemical shift

  9. Do We Know What Causes Breast Cancer?

    Science.gov (United States)

    ... Research? Breast Cancer About Breast Cancer How Does Breast Cancer Form? Changes or mutations in DNA can cause ... requests, please contact permissionrequest@cancer.org . More In Breast Cancer About Breast Cancer Risk and Prevention Early Detection ...

  10. microRNA miR-142-3p Inhibits Breast Cancer Cell Invasiveness by Synchronous Targeting of WASL, Integrin Alpha V, and Additional Cytoskeletal Elements.

    Directory of Open Access Journals (Sweden)

    Alexander Schwickert

    Full Text Available MicroRNAs (miRNAs, micro ribonucleic acids are pivotal post-transcriptional regulators of gene expression. These endogenous small non-coding RNAs play significant roles in tumorigenesis and tumor progression. miR-142-3p expression is dysregulated in several breast cancer subtypes. We aimed at investigating the role of miR-142-3p in breast cancer cell invasiveness. Supported by transcriptomic Affymetrix array analysis and confirmatory investigations at the mRNA and protein level, we demonstrate that overexpression of miR-142-3p in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells leads to downregulation of WASL (Wiskott-Aldrich syndrome-like, protein: N-WASP, Integrin-αV, RAC1, and CFL2, molecules implicated in cytoskeletal regulation and cell motility. ROCK2, IL6ST, KLF4, PGRMC2 and ADCY9 were identified as additional targets in a subset of cell lines. Decreased Matrigel invasiveness was associated with the miR-142-3p-induced expression changes. Confocal immunofluorescence microscopy, nanoscale atomic force microscopy and digital holographic microscopy revealed a change in cell morphology as well as a reduced cell volume and size. A more cortical actin distribution and a loss of membrane protrusions were observed in cells overexpressing miR-142-3p. Luciferase activation assays confirmed direct miR-142-3p-dependent regulation of the 3'-untranslated region of ITGAV and WASL. siRNA-mediated depletion of ITGAV and WASL resulted in a significant reduction of cellular invasiveness, highlighting the contribution of these factors to the miRNA-dependent invasion phenotype. While knockdown of WASL significantly reduced the number of membrane protrusions compared to controls, knockdown of ITGAV resulted in a decreased cell volume, indicating differential contributions of these factors to the miR-142-3p-induced phenotype. Our data identify WASL, ITGAV and several additional cytoskeleton-associated molecules as novel invasion-promoting targets of miR-142

  11. PD-L1 is a critical mediator of regulatory B cells and T cells in invasive breast cancer

    Science.gov (United States)

    Guan, Honggeng; Wan, Yuqiu; Lan, Jing; Wang, Qin; Wang, Zhangyu; Li, Yecheng; Zheng, Jiqing; Zhang, Xueguang; Wang, Zemin; Shen, Yueping; Xie, Fang

    2016-01-01

    Regulatory T cells (Tregs), a key mediator in regulating anti-tumor immune suppression, tumor immune escape, metastasis and relapse, are considered an important therapeutic target in immunotherapy of human cancers. In the present investigation, elevated CD19+ CD24+ CD38+ regulatory B cells (Bregs) were observed in PBMCs of invasive carcinoma of breast (IBCa) patients compared with that in patients with fibroadenoma (FIBma) or healthy individuals, and the positive correlation existed between Bregs and CD4+ CD25+ CD127− Tregs (r = 0.316, P = 0.001). We found that PD-L1 expression was higher on Bregs in IBCa patients compared with patients with FIBma or healthy individuals (P < 0.05, respectively), and that a tight correlation exists between CD19+ CD24+ CD38+ PD-L1+ Bregs and CD19+ CD24+ CD38+ Bregs (r = 0.267, P = 0.007), poor TNM phases and up-regulated expression of PD-L1 on Bregs. The pattern of PD-1 expression on CD4+ T cells indicated that high level of PD-1hi expressed on CD4+ CD25+ CD127+ effector T cells (P < 0.001). More importantly, the presence of PD-L1 on Bregs was positively correlated with Tregs (r = 0.299, P = 0.003), but negatively correlated with PD-1hi effector T cells (r = −0.22, P = 0.031). Together, results of the present study indicated that PD-L1 is an important molecule on Bregs, mediated the generation of Tregs in IBCa. PMID:27762298

  12. Chemotherapeutic Targeting of Fibulin-5 to Suppress Breast Cancer Invasion and Metastasis Simulated by Transforming Growth Factor-Beta

    Science.gov (United States)

    2012-01-01

    rates in patients with cancers of the brain , breast, lung, and blood. Our findings related to this novel FBLN5:fibromodulin signaling axis were...epithelial cells via a MMP-dependent mechanism. Carcinogenesis, 29, 2243-2251. [2] Bhowmick NA and Moses HL (2005). Tumor-stroma interactions. Curr...Opin Genet Dev, 15, 97- 101. 13 [3] Bhowmick NA, Neilson EG and Moses HL (2004). Stromal fibroblasts in cancer initiation and progression. Nature

  13. SPOCK1 Is a Novel Transforming Growth Factor-β-Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer.

    Science.gov (United States)

    Fan, Li-Ching; Jeng, Yung-Ming; Lu, Yueh-Tong; Lien, Huang-Chun

    2016-01-01

    In addition to contraction, myoepithelia have diverse paracrine effects, including a tumor suppression effect. However, certain myoepithelial markers have been shown to contribute to tumor progression. Transforming growth factor-β (TGF-β) is involved in the transdifferentiation of fibroblasts to contractile myofibroblasts. We investigated whether TGF-β can upregulate potential myoepithelial markers, which may have functional and clinicopathological significance in breast cancer. We found that TGF-β induced SPOCK1 expression in MCF10A, MCF12A, and M10 breast cells and demonstrated SPOCK1 as a novel myoepithelial marker that was immunolocalized within or beneath myoepithelia lining ductolobular units. A functional study showed that overexpression of SPOCK1 enhanced invasiveness in mammary immortalized and cancer cells. To further determine the biological significance of SPOCK1 in breast cancer, we investigated the expression of SPOCK1 in 478 invasive ductal carcinoma (IDC) cases through immunohistochemistry and correlated the expression with clinicopathological characteristics. SPOCK1 expression was significantly correlated with high pathological tumor size (P = 0.012), high histological grade (P = 0.013), the triple-negative phenotype (P = 0.022), and the basal-like phenotype (P = 0.026) and was correlated with a significantly poorer overall survival on univariate analysis (P = 0.001, log-rank test). Multivariate Cox regression analysis demonstrated that SPOCK1 expression maintained an independent poor prognostic factor of overall survival. Analysis of SPOCK1 expression on various non-IDC carcinoma subtypes showed an enrichment of SPOCK1 expression in metaplastic carcinoma, which is pathogenetically closely related to epithelial-mesenchymal transition (EMT). In conclusion, we identified SPOCK1 as a novel TGF-β-induced myoepithelial marker and further demonstrated that SPOCK1 enhanced invasion in breast cancer cells and correlated with poor prognosis in breast

  14. Exposure to parabens at the concentration of maximal proliferative response increases migratory and invasive activity of human breast cancer cells in vitro.

    Science.gov (United States)

    Khanna, Sugandha; Dash, Philip R; Darbre, Philippa D

    2014-09-01

    Alkyl esters of p-hydroxybenzoic acid (parabens) are widely used as preservatives in personal care products, foods and pharmaceuticals. Their oestrogenic activity, their measurement in human breast tissue and their ability to drive proliferation of oestrogen-responsive human breast cancer cells has opened a debate on their potential to influence breast cancer development. As proliferation is not the only hallmark of cancer cells, we have investigated the effects of exposure to parabens at concentrations of maximal proliferative response on migratory and invasive properties using three oestrogen-responsive human breast cancer cell lines (MCF-7, T-47-D, ZR-75-1). Cells were maintained short-term (1 week) or long-term (20 ± 2 weeks) in phenol-red-free medium containing 5% charcoal-stripped serum with no addition, 10(-8)  M 17β-oestradiol, 1-5 × 10(-4)  M methylparaben, 10(-5)  M n-propylparaben or 10(-5)  M n-butylparaben. Long-term exposure (20 ± 2 weeks) of MCF-7 cells to methylparaben, n-propylparaben or n-butylparaben increased migration as measured using a scratch assay, time-lapse microscopy and xCELLigence technology: invasive properties were found to increase in matrix degradation assays and migration through matrigel on xCELLigence. Western immunoblotting showed an associated downregulation of E-cadherin and β-catenin in the long-term paraben-exposed cells which could be consistent with a mechanism involving epithelial to mesenchymal transition. Increased migratory activity was demonstrated also in long-term paraben-exposed T-47-D and ZR-75-1 cells using a scratch assay and time-lapse microscopy. This is the first report that in vitro, parabens can influence not only proliferation but also migratory and invasive properties of human breast cancer cells.

  15. 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

  16. 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.

  17. 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

  18. Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated breast cancer: implications for tumor aggressiveness and invasiveness.

    Science.gov (United States)

    Xu, Zheli; Wang, Wan; Deng, Chu-Xia; Man, Yan-Gao

    2009-01-01

    Our recent studies revealed that focal alterations in breast myoepithelial cell layers significantly impact the biological presentation of associated epithelial cells. As pregnancy-associated breast cancer (PABC) has a significantly more aggressive clinical course and mortality rate than other forms of breast malignancies, our current study compared tumor suppressor expression in myoepithelial cells of PABC and non-PABC, to determine whether myoepithelial cells of PABC may have aberrant expression of tumor suppressors. Tissue sections from 20 cases of PABC and 20 cases of stage, grade, and age matched non-PABC were subjected to immunohistochemistry, and the expression of tumor suppressor maspin, p63, and Wilms' tumor 1 (WT-1) in calponin positive myoepithelial cells were statistically compared. The expression profiles of maspin, p63, and WT-1 in myoepithelial cells of all ducts encountered were similar between PABC and non-PABC. PABC, however, displayed several unique alterations in terminal duct and lobular units (TDLU), acini, and associated tumor tissues that were not seen in those of non-PABC, which included the absence of p63 and WT-1 expression in a vast majority of the myoepithelial cells, cytoplasmic localization of p63 in the entire epithelial cell population of some lobules, and substantially increasing WT-1 expression in vascular structures of the invasive cancer component. All or nearly all epithelial cells with aberrant p63 and WT-1 expression lacked the expression of estrogen receptor and progesterone receptor, whereas they had a substantially higher proliferation index than their counterparts with p63 and WT-1 expression. Hyperplastic cells with cytoplasmic p63 expression often adjacent to, and share a similar immunohistochemical and cytological profile with, invasive cancer cells. To our best knowledge, our main finings have not been previously reported. Our findings suggest that the functional status of myoepithelial cells may be significantly

  19. Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated breast cancer: implications for tumor aggressiveness and invasiveness

    Directory of Open Access Journals (Sweden)

    Zheli Xu, Wan Wang, Chu-Xia Deng, Yan-gao Man

    2009-01-01

    Full Text Available Our recent studies revealed that focal alterations in breast myoepithelial cell layers significantly impact the biological presentation of associated epithelial cells. As pregnancy-associated breast cancer (PABC has a significantly more aggressive clinical course and mortality rate than other forms of breast malignancies, our current study compared tumor suppressor expression in myoepithelial cells of PABC and non-PABC, to determine whether myoepithelial cells of PABC may have aberrant expression of tumor suppressors. Tissue sections from 20 cases of PABC and 20 cases of stage, grade, and age matched non-PABC were subjected to immunohistochemistry, and the expression of tumor suppressor maspin, p63, and Wilms' tumor 1 (WT-1 in calponin positive myoepithelial cells were statistically compared. The expression profiles of maspin, p63, and WT-1 in myoepithelial cells of all ducts encountered were similar between PABC and non-PABC. PABC, however, displayed several unique alterations in terminal duct and lobular units (TDLU, acini, and associated tumor tissues that were not seen in those of non-PABC, which included the absence of p63 and WT-1 expression in a vast majority of the myoepithelial cells, cytoplasmic localization of p63 in the entire epithelial cell population of some lobules, and substantially increasing WT-1 expression in vascular structures of the invasive cancer component. All or nearly all epithelial cells with aberrant p63 and WT-1 expression lacked the expression of estrogen receptor and progesterone receptor, whereas they had a substantially higher proliferation index than their counterparts with p63 and WT-1 expression. Hyperplastic cells with cytoplasmic p63 expression often adjacent to, and share a similar immunohistochemical and cytological profile with, invasive cancer cells. To our best knowledge, our main finings have not been previously reported. Our findings suggest that the functional status of myoepithelial cells may be

  20. Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Christiansen, Peer; Ejlertsen, Bent; Jensen, Maj-Britt

    2016-01-01

    AIM OF DATABASE: Danish Breast Cancer Cooperative Group (DBCG), with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive...... of adherence to the guidelines in the different departments. CONCLUSION: Utilizing data from the DBCG database, a long array of high-quality DBCG studies of various designs and scope, nationwide or in international collaboration, have contributed to the current updating of the guidelines, and have been...

  1. Immunohistochemical analysis of cancer stem cell markers in invasive breast carcinoma and associated ductal carcinoma in situ: relationships with markers of tumor hypoxia and microvascularity.

    Science.gov (United States)

    Currie, Margaret J; Beardsley, Brooke E; Harris, Gavin C; Gunningham, Sarah P; Dachs, Gabi U; Dijkstra, Birgit; Morrin, Helen R; Wells, J Elisabeth; Robinson, Bridget A

    2013-03-01

    We performed immunohistochemical analysis of 3 cancer stem cell-related markers (CD44(+)/CD24(-/low), aldehyde dehydrogenase [ALDH]-1, CD133) in 94 invasive ductal carcinomas and assessed relationships with markers of hypoxia (carbonic anhydrase IX [CAIX]), tumor microvessel density (CD31), and clinicopathologic variables. Overall, 10% of tumors were CD44(+)/CD24(-/low), 13% were ALDH-1(+), 25% were CD133(+), 35% were immunonegative, and 1 tumor was immunopositive for all 3 markers. Associated ductal carcinoma in situ (DCIS) was present in 48% of tumors. Marker immunopositivity was detected in DCIS in 13% (CD44(+)/CD24(-/low)), 7% (ALDH-1(+)), and 32% (CD133(+)) of these tumors and was more likely present in DCIS when also detected in the invasive compartment (P = .03, P = .001, and P = .009, respectively). CD44(+)/CD24(-/low) cells were more common in progesterone receptor-negative tumors (P breast cancers (P breast cancer and showed that CD44(+)/CD24(-/low) and CD133(+) cells were more frequently observed in hypoxic regions of tumor, whereas ALDH-1(+) cells more commonly colocalized to tumors with high microvessel density.

  2. 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

  3. Dynamics of cancerous tissue correlates with invasiveness

    Science.gov (United States)

    West, Ann-Katrine Vransø; Wullkopf, Lena; Christensen, Amalie; Leijnse, Natascha; Tarp, Jens Magelund; Mathiesen, Joachim; Erler, Janine Terra; Oddershede, Lene Broeng

    2017-01-01

    Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion. PMID:28262796

  4. Dynamics of cancerous tissue correlates with invasiveness

    Science.gov (United States)

    West, Ann-Katrine Vransø; Wullkopf, Lena; Christensen, Amalie; Leijnse, Natascha; Tarp, Jens Magelund; Mathiesen, Joachim; Erler, Janine Terra; Oddershede, Lene Broeng

    2017-03-01

    Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

  5. Breast Cancer in Men

    Science.gov (United States)

    ... Older age • B RCA2 gene mutation • F amily history of breast cancer • Gynecomastia (enlargement of the breast tissue) • Klinefelter’s syndrome (a genetic condition related to high levels ...

  6. Hippo pathway in mammary gland development and breast cancer.

    Science.gov (United States)

    Shi, Peiguo; Feng, Jing; Chen, Ceshi

    2015-01-01

    Accumulated evidence suggests that the Hippo signaling pathway plays crucial roles in mammary gland development and breast cancer. Key components of the Hippo pathway regulate breast epithelial cell proliferation, migration, invasion, and stemness. Additionally, the Hippo pathway regulates breast tumor growth, metastasis, and drug resistance. It is expected that the Hippo pathway will provide novel therapeutic targets for breast cancer. This review will discuss and summarize the roles of several core components of the Hippo pathway in mammary gland development and breast cancer.

  7. 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...

  8. 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.

  9. Feature Extraction and Analysis of Breast Cancer Specimen

    Science.gov (United States)

    Bhattacharyya, Debnath; Robles, Rosslin John; Kim, Tai-Hoon; Bandyopadhyay, Samir Kumar

    In this paper, we propose a method to identify abnormal growth of cells in breast tissue and suggest further pathological test, if necessary. 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 greater extent.

  10. 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

  11. 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.

  12. 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

  13. WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion

    Science.gov (United States)

    García, Esther; Ragazzini, Chiara; Yu, Xinzi; Cuesta-García, Elena; Bernardino de la Serna, Jorge; Zech, Tobias; Sarrió, David; Machesky, Laura M.; Antón, Inés M.

    2016-01-01

    Cancer cells form actin-rich degradative protrusions (invasive pseudopods and invadopodia), which allows their efficient dispersal during metastasis. Using biochemical and advanced imaging approaches, we demonstrate that the N-WASP-interactors WIP and WICH/WIRE play non-redundant roles in cancer cell invasion. WIP interacts with N-WASP and cortactin and is essential for invadopodium assembly, whereas WICH/WIRE regulates N-WASP activation to control invadopodium maturation and degradative activity. Our data also show that Nck interaction with WIP and WICH/WIRE modulates invadopodium maturation; changes in WIP and WICH/WIRE levels induce differential distribution of Nck. We show that WIP can replace WICH/WIRE functions and that elevated WIP levels correlate with high invasiveness. These findings identify a role for WICH/WIRE in invasiveness and highlight WIP as a hub for signaling molecule recruitment during invadopodium generation and cancer progression, as well as a potential diagnostic biomarker and an optimal target for therapeutic approaches. PMID:27009365

  14. 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.

  15. 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.

  16. 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

  17. Radiotherapy in the management of early breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei [Westmead Breast Cancer Institute, Westmead Hospital, Westmead, New South Wales (Australia); Department of Radiation Oncology, Westmead Hospital, New South Wales (Australia)

    2013-03-15

    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 that underpin our current practice are discussed briefly.

  18. Angiogenesis in male breast cancer

    Directory of Open Access Journals (Sweden)

    Kanthan Rani

    2005-03-01

    Full Text Available Abstract Background Male breast cancer is a rare but aggressive and devastating disease. This disease presents at a later stage and in a more advanced fashion than its female counterpart. The immunophenotype also appears to be distinct when compared to female breast cancer. Angiogenesis plays a permissive role in the development of a solid tumor and provides an avenue for nutrient exchange and waste removal. Recent scrutiny of angiogenesis in female breast cancer has shown it to be of significant prognostic value. It was hypothesized that this holds true in invasive ductal carcinoma of the male breast. In the context of male breast cancer, we investigated the relationship of survival and other clinico-pathological variables to the microvascular density of the tumor tissue. Methods Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Agency over a period of 26 years. Forty-seven cases of invasive ductal carcinoma of the male breast had formalin-fixed paraffin-embedded tissue blocks that were suitable for this study. All cases were reviewed. Immunohistochemical staining was performed for the angiogenic markers (cluster designations 31 (CD31, 34 (CD34 and 105 (CD105, von Willebrand factor (VWF, and vascular endothelial growth factor (VEGF. Microvascular density (MVD was determined using average, centre, and highest microvessel counts (AMC, CMC, and HMC, respectively. Statistical analyses compared differences in the distribution of survival times and times to relapse between levels of MVD, tumor size, node status and age at diagnosis. In addition, MVD values were compared within each marker, between each marker, and were also compared to clinico-pathological data. Results Advanced age and tumor size were related to shorter survival times. There were no statistically significant differences in distributions of survival times and times to relapse between levels of MVD variables. There was no

  19. Mitochondrial dysfunction promotes breast cancer cell migration and invasion through HIF1α accumulation via increased production of reactive oxygen species.

    Directory of Open Access Journals (Sweden)

    Jia Ma

    Full Text Available Although mitochondrial dysfunction has been observed in various types of human cancer cells, the molecular mechanism underlying mitochondrial dysfunction mediated tumorigenesis remains largely elusive. To further explore the function of mitochondria and their involvement in the pathogenic mechanisms of cancer development, mitochondrial dysfunction clones of breast cancer cells were generated by rotenone treatment, a specific inhibitor of mitochondrial electron transport complex I. These clones were verified by mitochondrial respiratory defect measurement. Moreover, those clones exhibited increased reactive oxygen species (ROS, and showed higher migration and invasive behaviors compared with their parental cells. Furthermore, antioxidant N-acetyl cysteine, PEG-catalase, and mito-TEMPO effectively inhibited cell migration and invasion in these clones. Notably, ROS regulated malignant cellular behavior was in part mediated through upregulation of hypoxia-inducible factor-1 α and vascular endothelial growth factor. Our results suggest that mitochondrial dysfunction promotes cancer cell motility partly through HIF1α accumulation mediated via increased production of reactive oxygen species.

  20. 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.

  1. 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.

  2. [Male breast cancer: a challenge for urologists].

    Science.gov (United States)

    Hofer, C; Schmalfeldt, B; Gschwend, J E; Herkommer, K

    2010-09-01

    Male breast cancer (male BC) accounts for Klinefelter syndrome) and a positive family history for breast cancer. About 90% of male BC are invasive ductal carcinomas. Standard treatment for localized cancer is surgical removal. Adjuvant radiation and systemic therapy are the same as in women with breast cancer. Male BC expresses hormone receptors in about 90% of cases; therefore, tamoxifen is a therapeutic option. A future challenge for the urologist or andrologist is to diagnose the disease at an early stage to improve prognosis.

  3. Optimized polymerase chain reaction-based single-strand conformation polymorphism analysis of p53 gene applied to Bulgarian patients with invasive breast cancer.

    Science.gov (United States)

    Krasteva, M E; Garanina, Z; Georgieva, E I

    2003-11-01

    During the last few decades a substantial amount of evidence has accumulated proving that the abrogation of the normal p53 pathway is a critical step in the initiation and progression of tumors. Decoding the genetic mechanisms involved in carcinogenesis requires screening for consistent genetic tumor alterations, including those concerning the p53 gene. Thus, practical, efficient, and inexpensive techniques for accurate determination of p53 mutational status are needed. Polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis is considered to be a useful tool to investigate the role of the p53 gene in the development and progression of human cancers. The sensitivity of the method can be increased considerably by varying the experimental conditions. Here we demonstrate a scheme of PCR-SSCP optimization for detection of p53 gene mutations of patients with various cancers. Optimal conditions for PCRSSCP of p53 exons 4-9 are reported. Such PCR-SSCP optimization could allow an increase in the sensitivity and reproducibility of the technique and facilitates screening of large series of patients to assess the clinical significance of p53 mutations in human cancers. Using the optimized PCR-SSCP analysis we screened Bulgarian patients with invasive breast cancer for p53 gene mutations and registered a 33.33% frequency of mutations. To date, there are no data concerning the p53 status of Bulgarian breast cancer patients. Screening for p53 gene mutations enables an accurate and routine determination of the p53 status of patients with cancer and may be applied in clinical oncology to cancer diagnosis, prediction of prognosis and response to treatment.

  4. 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...

  5. Minimally invasive approach to neoplastic breast disease

    NARCIS (Netherlands)

    Waaijer, L.

    2015-01-01

    Surgical excision is considered the primary treatment for breast cancer. Potentially less deforming approaches such as in situ ablative treatments aim to preserve the greatest amount of normal breast tissue. Previous studies on radiofrequency ablation (RFA) for the local control of small breast canc

  6. Oncogenic role of SIRT1 associated with tumor invasion, lymph node metastasis, and poor disease-free survival in triple negative breast cancer.

    Science.gov (United States)

    Chung, Soo Young; Jung, Yoon Yang; Park, In Ae; Kim, Hyojin; Chung, Yul Ri; Kim, Ji Young; Park, Soo Young; Im, Seock-Ah; Lee, Kyung-Hun; Moon, Hyeong-Gon; Noh, Dong-Young; Han, Wonshik; Lee, Chul; Kim, Tae-Yong; Ryu, Han Suk

    2016-02-01

    The aim of this study is to evaluate the biological role and clinical implications of silent mating type information regulation 2 homolog 1 (SIRT1) as a novel candidate for target therapy in triple negative breast cancer (TNBC) for which there is no specific agent. 344 patients who received surgical resection for TNBC from January 2003 to December 2006 at Seoul National University Hospital were enrolled, and the role of SIRT1 protein was evaluated via immunohistochemistry on tissue samples. In vivo experiments to evaluate tumor invasiveness were carried out with three human TNBC cell lines following SIRT1-siRNA transfection. Expression of SIRT1 significantly correlated with lymph node metastasis (p = 0.008). In multivariate analysis, SIRT1 expression (p = 0.011), T stage (p = 0.014), and lymphatic invasion (p SIRT1 expression correlated with shorter disease-free survival (P = 0.003) but not with overall survival. Inhibition of SIRT1 with small interfering RNA (siRNA) conspicuously suppressed the invasiveness of TNBC cell lines. This study reveals the role of SIRT1 on tumor invasiveness and unfavorable clinical outcomes, and we suggest its potential role as a prognostic indicator as well as a novel therapeutic target in TNBC.

  7. Breast cancer

    Science.gov (United States)

    ... women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2014;160:271-281. PMID: 24366376 www.ncbi. ... Cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . [Epub ahead of print 12 January 2016] doi: ...

  8. 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

  9. BREAST CANCER AND EXERCISE

    Science.gov (United States)

    2008-03-19

    Prevent Osteoporosis and Osteoporotic Fractures; Improve Quality of Life; Improve Weight Control, and Muscular and Cardiovascular Fitness; Help the Patients to Return to Working Life; Reduce the Risk of Breast Cancer Recurrence; Prevent Other Diseases and Reduce All-Cause Mortality in Patients With Primary Breast Cancer.

  10. Inhibitory effect of salinomycin on invasion of breast cancer cells%盐霉素对乳腺癌转移的抑制作用

    Institute of Scientific and Technical Information of China (English)

    赵月; 沈娜; 任精华; 赵向旺; 黄韬; 何文山

    2013-01-01

    Objective To study the effects of salinomycin on the proliferation and invasion of breast cancer cells and the mechanism.Methods The human breast cancer cells MCF-7,MCF-7/ADR and MDA-MB-231,were treated with salinomycin.Cell viability was determined by cell counting kit-8.The invasive ability of tumor cells was evaluated by Transwell chamber assay.The mRNA and protein levels of ETS1 and matrix metalloproteinase (MMP)-1 were detected by using real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting respectively.Results Salinomycin significantly inhibited the proliferation of breast cancer cells with the IC50 value being (7.47 ±0.64) for MCF-7,(5.11 ±0.97) for MCF-7/ADR,and (4.08 ±0.85) μmol/L for MDA-MB-231,respectively.The invasion capacity of breast cancer cells were significantly reduced by salinomycin (65.9%/41.9% for MCR-7,55.8% /37.8% for MCR-7/ADR,and 48.5%/24.6% for MDA-MB-23I,respectivel).Simustaneously,the expression levels of ETS1 and MMP-1 were downregulated by salinomycin.Conclusion Salinomycin can inhibit the proliferation of breast cancer cells,and reduce the invasion capacity.%目的 观察盐霉素对乳腺癌细胞株MCF-7、MCF-7/ADR、MDA-MB-231的体外增殖和侵袭能力的影响,探讨其对乳腺癌细胞的转移抑制作用.方法 用细胞计数试剂盒(CCK-8)法检测细胞增殖,得出半数抑制浓度(IC50)值;用Transwell小室法检测侵袭能力的变化;分别用实时定量聚合酶链反应(Real-time PCR)法和Western blot法检测ETS1和基质金属蛋白酶(MMP)-1基因和蛋白的表达变化.结果 盐霉素抑制乳腺癌细胞的增殖,3种细胞的IC50值分别为(7.47 ±0.64)、(5.11±0.97)、(4.08±0.85)μmol/L;经不同浓度的盐霉素处理后,3种细胞侵袭能力逐渐下降,分别为对照组的65.9%/41.9%、55.8%/37.8%、48.5%/24.6%;MCF-7/ADR和MDA-MB-231的ETS1和MMP-1表达水平随着盐霉素浓度升高而下降.结论 盐霉素可以抑

  11. Is clinical breast examination important for breast cancer detection?

    Science.gov (United States)

    Provencher, L.; Hogue, J.C.; Desbiens, C.; Poirier, B.; Poirier, E.; Boudreau, D.; Joyal, M.; Diorio, C.; Duchesne, N.; Chiquette, J.

    2016-01-01

    Background Screening clinical breast examination (cbe) is controversial; the use of cbe is declining not only as a screening tool, but also as a diagnostic tool. In the present study, we aimed to assess the value of cbe in breast cancer detection in a tertiary care centre for breast diseases. Methods This retrospective study of all breast cancers diagnosed between July 1999 and December 2010 at our centre categorized cases according to the mean of detection (cbe, mammography, or both). A cbe was considered “abnormal” in the presence of a mass, nipple discharge, skin or nipple retraction, edema, erythema, peau d’orange, or ulcers. Results During the study period, a complete dataset was available for 6333 treated primary breast cancers. Cancer types were ductal carcinoma in situ (15.3%), invasive ductal carcinoma (75.7%), invasive lobular carcinoma (9.0%), or others (2.2%). Of the 6333 cancers, 36.5% (n = 2312) were detected by mammography alone, 54.8% (n = 3470) by mammography and cbe, and 8.7% (n = 551) by physician-performed cbe alone (or 5.3% if considering ultrasonography). Invasive tumours diagnosed by cbe alone were more often triple-negative, her2-positive, node-positive, and larger than those diagnosed by mammography alone (p < 0.05). Conclusions A significant number of cancers would have been missed if cbe had not been performed. Compared with cancers detected by mammography alone, those detected by cbe had more aggressive features. Clinical breast examination is a very low-cost test that could improve the detection of breast cancer and could prompt breast ultrasonography in the case of a negative mammogram. PMID:27536182

  12. CDC Vital Signs: Breast Cancer

    Science.gov (United States)

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

  13. Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules.

    Science.gov (United States)

    Vasse, M; Thibout, D; Paysant, J; Legrand, E; Soria, C; Crépin, M

    2001-03-23

    Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1.

  14. 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.

  15. 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

  16. Breast cancer in Singapore: some perspectives.

    Science.gov (United States)

    Jara-Lazaro, Ana Richelia; Thilagaratnam, Shyamala; Tan, Puay Hoon

    2010-01-01

    Breast cancer is the commonest malignancy among Singapore women, accounting for 29.7% of all female cancers, with an age-standardized rate of 54.9 per 100,000 per year. It has been the most frequent cancer in Singapore women for the last 30 years, with the highest rates previously reported in those aged between 45 and 49 years, but with a more recent observation of a change in peak age group to women in their late 50s. About 1,100 new cases are diagnosed annually and approximately 270 women die in Singapore each year from breast cancer. In the multiethnic population of Singapore, it has been noted that rising breast cancer incidence is consistent across all three ethnic groups (Chinese, Malays, and Indians). Singapore has among the highest breast cancer incidence in Asia. Possible explanations include rapid urbanization, improvement in socio-economic status, and adoption of a western lifestyle. Our experience with the Singapore breast screening pilot project (1994-1997) and the national breast-screening program (BreastScreen Singapore) has led to increased understanding of this disease in the country. Data from the pilot project showed that breast screening is just as effective in a predominantly Asian population as in the west. Early breast cancer accounted for most breast cancers detected, with pre-invasive ductal carcinoma in situ (DCIS) comprising 26% of all screen-detected cancers in the pilot study. In the currently on-going BreastScreen Singapore, DCIS forms >30% of all breast cancers among pre-menopausal women, a relatively high proportion probably accounted for partially by the greater participation of women aged between 40 and 49 years. Despite the ready availability of subsidized mammographic screening, there are still women in Singapore who present with locally advanced breast cancer. Clinical management of an increasing number of women with breast cancer embraces a multidisciplinary team-based approach, with regular discussions of therapeutic

  17. 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.)

  18. 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 ...

  19. Embelin Inhibits Invasion and Migration of MDA-MB-231 Breast Cancer Cells by Suppression of CXC Chemokine Receptor 4, Matrix Metalloproteinases-9/2, and Epithelial-Mesenchymal Transition.

    Science.gov (United States)

    Lee, Hanwool; Ko, Jeong-Hyeon; Baek, Seung Ho; Nam, Dongwoo; Lee, Seok Geun; Lee, Junhee; Yang, Woong Mo; Um, Jae-Young; Kim, Sung-Hoon; Shim, Bum Sang; Ahn, Kwang Seok

    2016-06-01

    Embelin (EB) is a benzoquinone derivative isolated from Embelia ribes Burm plant. Recent scientific evidence shows that EB induces apoptosis and inhibits migration and invasion in highly metastatic human breast cancer cells. However, the exact mechanisms of EB in tumor metastasis and invasion have not been fully elucidated. Here, we investigated the underlying mechanisms of antimetastatic activities of EB in breast cancer cells. The EB downregulated the chemokine receptor 4 (CXCR4) as well as matrix metalloproteinase (MMP)-9/2 expression and upregulated the tissue inhibitor of metalloproteinase 1 expression in MDA-MB-231 cells under noncytotoxic concentrations but not in MCF-7 cells. Additionally, EB inhibited the CXC motif chemokine ligand 12 induced invasion and migration activities of MDA-MB-231 cells. A detailed study of underlying mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by the downregulation of mRNA expression and suppression of nuclear factor-kappa B (NF-κB) activation. It further reduced the binding of NF-κB to the CXCR4 promoter. Besides, EB downregulated mesenchymal marker proteins (neural cadherin and vimentin) and concurrently upregulated epithelial markers (epithelial cadherin and occludin). Overall, these findings suggest that EB can abrogate breast cancer cell invasion and metastasis by suppression of CXCR4, MMP-9/2 expressions, and inhibition of epithelial-mesenchymal transition and thus may have a great potential to suppress metastasis of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.

  20. 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.

  1. 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

  2. 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.

  3. [THE EFFECT OF PREGNANCY ON BREAST CANCER].

    Science.gov (United States)

    Matalon, Shelly Tartakover; Shochet, Gali Epstein; Drucker, Liat; Lishner, Michael

    2015-08-01

    Cancer and pregnancy coincide in about one in 1,000 pregnancies. One of the most common malignancies associated with pregnancy is breast cancer. Women with pregnancy-associated breast cancer (PABC) have a higher likelihood of being diagnosed with metastatic disease and estrogen receptor (ER) negative tumors than do non-pregnant women. Controversies exist regarding the effect of pregnancy on breast cancer prognosis. Some researchers suggest that pregnancy does not affect breast cancer prognosis, whereas others claim the opposite. Although PABC is usually discovered in an advanced stage, breast cancer metastasis on the placenta is a rare event. During cancer progression, the surrounding microenvironment co-evolves into an activated state through continuous communication with the malignant cells, thereby promoting tumor growth. The effect of pregnancy and placental environment on breast cancer biology is the issue of this review. Placental and cancer cells implantation processes share similar molecular pathways. This suggests that placental factors may affect breast cancer cells biology. Previously, we analyzed the effect of first trimester human placenta on breast cancer cells. Breast cancer cells were co-cultured with placental explants during their implantation on matrigel substrate. We found that the placenta reduced ER expression on the cancer cells and induced their migration and invasion abilities. As a result of it, breast cancer cells migrated away from the placental implantation sites. Hormonal pathways were involved in these phenomena. These results may explain the high incidence of metastases during pregnancy in on the one hand and the rarity of metastases on the placenta on the other hand.

  4. Experimental co-expression of vimentin and keratin intermediate filaments in human breast cancer cells results in phenotypic interconversion and increased invasive behavior.

    Science.gov (United States)

    Hendrix, M J; Seftor, E A; Seftor, R E; Trevor, K T

    1997-02-01

    The expression of intermediate filament proteins is remarkably tissue specific, which suggests that the intermediate filament type(s) present in cells is somehow related to their biological function. However, in some cancers, particularly malignant breast carcinoma, there is a strong indication that vimentin is co-expressed with keratins, thus presenting as a dedifferentiated or interconverted (between epithelial and mesenchymal) phenotype. In the present study, we recapitulated the interconverted phenotype by developing stable transfectants of MCF-7 human breast cancer cells, termed MoVi clones, to express both vimentin and keratins. Overexpression of vimentin in these cells led to augmentation of motility and invasiveness in vitra. These activities could be transiently down-regulated by vimentin antisense oligonucleotides in MoVi clones and MDA-MB-231 cells (which constitutively co-express keratins and vimentin). Furthermore, in the MoVi experimental transfectants expressing the highest percentage of vimentin-positive cells, their proliferative capacity, clonogenic potential, and tumorigenicity increased. However, the metastatic ability of the MoVi transfectants remained unchanged compared with MCF-7neo controls. The MDA-MB-231 cells metastasized to axillary lymph nodes in a SCID mouse model. Finally, we explored the possibility that potential changes could occur with respect to cell surface integrins. These studies revealed a decrease in the alpha 2- and alpha 3-containing promiscuous integrins, in addition to beta 1 containing integrins, concomitant with an increase in the alpha 6-containing laminin receptor integrin. Further functional analysis of the alpha 6 observation showed an increase in the baptotactic migration of MoVi transfectants toward a laminin substrate. From these data, it is postulated that the ability to co-express vimentin and keratins confers a selective advantage to breast cancer cells in their interpretation of signaling cues from the

  5. 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

  6. Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases.

    Science.gov (United States)

    Hagemann, Thorsten; Robinson, Stephen C; Schulz, Matthias; Trümper, Lorenz; Balkwill, Frances R; Binder, Claudia

    2004-08-01

    Apart from the neoplastic cells, malignant tumours consist of the extracellular matrix (ECM) and normal cells, in particular tumour-associated macrophages (TAM). To understand the mechanisms by which TAM can influence tumour cell invasion we co-cultured the human breast cancer cell lines MCF-7, SK-BR-3 and the benign mammary epithelial cell line hTERT-HME1 with macrophages. Co-incubation enhanced invasiveness of the tumour cells, while hTERT-HME1 remained non-invasive. Addition of the broad-spectrum matrix metalloprotease (MMP)-inhibitor FN 439, neutralizing MMP-9 or tumour necrosis factor-alpha (TNF-alpha) antibodies reduced invasiveness to basal levels. As shown by zymography, all cell lines produced low amounts of MMP-2, -3, -7 and -9 under control conditions. Basal MMP production by macrophages was significantly higher. Upon co-incubation, supernatant levels of MMPs -2, -3, -7 and -9 increased significantly, paralleled by an increase of MMP-2 activation. MMP-2 and -9 induction could be blocked by TNF-alpha antibodies. Co-culture of macrophages and hTERT-HME1 did not lead to MMP induction. In the co-cultures, mRNAs for MMPs and TNF-alpha were significantly up-regulated in macrophages, while the mRNA concentrations in the tumour cells remained unchanged. In summary, we have found that co-cultivation of tumour cells with macrophages leads to enhanced invasiveness of the malignant cells due to TNF-alpha dependent MMP induction in the macrophages.

  7. Can Radiography Be Used to Exclude Negative Margins in Breast Cancer Specimens?

    Science.gov (United States)

    2002-09-01

    carcinoma in-situ (DCIS) cases were included in this study. There were 66 (68%) invasive cancers, 29 (30%) cases of DCIS only, and 2 phyllodes tumors ...Achieving tumor -free margins is an important clinical goal in breast conservation surgery for the treatment of breast cancer. This prospective...cancers: invasive, in-situ, and phyllodes Invasive cancer Invasive ductal carcinoma, not otherwise specified 44 (45%) Invasive carcinoma, mixed

  8. Breast Cancer in Young Women

    Science.gov (United States)

    ... NPCR 2017 CDC National Cancer Conference Stay Informed Breast Cancer in Young Women Recommend on Facebook Tweet Share Compartir Syndicate this page Marleah's family history of breast cancer was her motivation for pursuing a career where ...

  9. Breast Cancer In Women

    Science.gov (United States)

    This infographic shows the Breast Cancer Subtypes in Women. It’s important for guiding treatment and predicting survival. Know the Science: HR = Hormone receptor. HR+ means tumor cells have receptors for the hormones estrogen or progesterone, which can promote the growth of HR+ tumors. Hormone therapies like tamoxifen can be used to treat HR+ tumors. HER2 = Human epidermal growth Factor receptor, HER2+ means tumor cells overexpress (make high levels of) a protein, called HE2/neu, which has been shown to be associated with certain aggressive types of breast cancer. Trastuzumab and some other therapies can target cells that overexpress HER2. HR+/HER2, aka “LuminalA”. 73% of all breast cancer cases: best prognosis, most common subtype for every race, age, and poverty level. HR-/HER2, aka “Triple Negative”: 13% of all breast cancer cases, Worst prognosis, Non-Hispanic blacks have the highest rate of this subtype at every age and poverty level. HR+/HER2+, aka “Luminal B”, 10% of all breast cancer cases, little geographic variation by state. HR-/HER2+, aka”HER2-enriched”, 5% of all breast cancer cases, lowest rates for all races and ethnicities. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  10. 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

  11. 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.

  12. 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.

  13. SIRT1 induces tumor invasion by targeting epithelial mesenchymal transition-related pathway and is a prognostic marker in triple negative breast cancer.

    Science.gov (United States)

    Jin, Min-Sun; Hyun, Chang Lim; Park, In Ae; Kim, Ji Young; Chung, Yul Ri; Im, Seock-Ah; Lee, Kyung-Hun; Moon, Hyeong-Gon; Ryu, Han Suk

    2016-04-01

    Absence of therapeutic targets poses a critical hurdle in improving prognosis for patients with triple negative breast cancer (TNBC). We evaluated interaction between SIRT1 and epithelial mesenchymal transition (EMT)-associated proteins as well as the role of combined protein expression as a predictor of lymph node metastasis and clinical outcome in TNBC through in vivo and vitro studies. Three hundred nineteen patients diagnosed with TNBC were chosen, immunohistochemical staining for SIRT1 and EMT-related markers' expression was performed on tissue microarrays, and in vitro experiments with each of the three human TNBC cell lines were carried out. The cohort was reclassified according to the use of adjuvant chemotherapy, tumor size, and AJCC stage to analyze the prognostic role of SIRT1 and EMT-related proteins' expression considering different therapeutic modalities and AJCC stages. Combination of four proteins including SIRT1 and three EMT-related proteins was revealed to be a statistically significant independent predictor of lymph node metastasis in the tumor size cohort as well as in the total patient population. Upon Cox regression analysis, increased expression level of the combined proteins correlated with decreased disease-free survival in the total patients as well as those who received adjuvant chemotherapy and those who had early stage breast cancer. In additional in vitro experiments, inhibition of SIRT1 expression with small interfering RNA (siRNA) suppressed tumor invasion in three different TNBC cell lines, and altered expression levels of EMT-related proteins following SIRT1 gene inhibition were identified on western blotting and fluorescence activated cell sorting (FACS) analysis; on the other hand, no change in expression levels of the cell cycle-related factors was observed. Our analysis showed the potential role of SIRT1 in association with EMT-related factors on tumor invasion, metastasis, and disease-free survival in TNBC, SIRT1, and

  14. Hormone receptors in breast cancer

    NARCIS (Netherlands)

    Suijkerbuijk, K. P M; van der Wall, E.; van Diest, P. J.

    2016-01-01

    Steroid hormone receptors are critical for the growth and development of breast tissue as well as of breast cancer. The importance of the role estrogens in breast cancer has been delineated for more than 100 years. The analysis of its expression has been used not only to classify breast cancers but

  15. 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...

  16. Invasive Papillary Carcinoma of the Male Breast Misdiagnosed as Fibroadenoma on FNAB

    Science.gov (United States)

    Katiyar, Richa; Kumar, Sandip; Khanna, Rahul

    2017-01-01

    Male breast cancers constitute less than 1% of all the breast cancers. Papillary carcinoma is a very rare tumour of the male breast. Due to rarity, Fine Needle Aspiration Biopsy (FNAB) findings of papillary carcinoma in male breast are seldom reported. A 55-year-old male presented with a lump in the left breast of two years’ duration. FNAB was reported as fibroadenoma. Histopathological examination of the excised breast lump revealed invasive papillary carcinoma. Immunohistochemistry showed expression of pancytokeratin, oestrogen receptor, and progesterone receptor. Negative immunostaining was seen for HER2, p53, 34βE12, and CD34. Ki-67 proliferative index was 5%. We have discussed cytological findings of invasive papillary carcinoma and its differential diagnoses. Cytopathologists must be aware of cytologic findings of invasive papillary carcinoma of the male breast. PMID:28384872

  17. Upregulation of microRNA-181b inhibits CCL18-induced breast cancer cell metastasis and invasion via the NF-κB signaling pathway.

    Science.gov (United States)

    Wang, Lei; Wang, Yu-Xia; Chen, Li-Ping; Ji, Ming-Li

    2016-12-01

    The purpose of the present study was to investigate the effects of upregulating microRNA (miR)-181b expression in tumor-associated macrophages regarding breast cancer cell metastasis and to identify the target gene. Ectopic miR-181b was transfected into MDA-MB-231 and MCF-7 breast cancer cell lines with or without chemokine ligand 18 (CCL18) stimulation. Cell proliferation, migration/invasion and apoptosis rate were investigated. The binding effects of miR-181b to the 3'-untranslated region (UTR) of the nuclear factor (NF)-κB gene were detected with the dual luciferase reporter system. Immunofluorescent staining of the NF-κB key component P65 was performed. The messenger (m) RNA and protein expression of NF-κB induced by CCL18 with or without miR-181b stimulation was evaluated with reverse transcription-quantitative polymerase chain reaction and western blot analysis. When compared with the CCL18-stimulated group, miR-181b mimic-transfected cells exhibited significantly inhibited proliferation and migration, with an increased cell apoptosis percentage in a dose-dependent manner. Furthermore, the luciferase activity was reduced for cells with NF-κB 3'-UTR wild-type that were co-transfected with miR-181b mimics. Immunofluorescent staining of NF-κB demonstrably weakened the P65 signal in stimulated miR-181b mimic cells when compared with parental and CCL18-treated cells. The increased expression level of NF-κB induced by CCL18 in MDA-MB-231 and MCF-7 cells was suppressed by miR-181b mimics. Overexpression of miR-181b suppressed cell survival rate and migration. This overexpression may achieve this goal by regulating the NF-κB pathway in breast cancer cells. Our study demonstrated a potential therapeutic application of miR-181b in the treatment of breast cancer.

  18. 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.

  19. 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.

  20. 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

  1. 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...

  2. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... means they developed from cells that line the milk ducts of the breast and then spread beyond ...

  3. Recurrent Breast Cancer

    Science.gov (United States)

    ... that can help you cope with distress include: Art therapy Dance or movement therapy Exercise Meditation Music ... mayoclinic.org/diseases-conditions/recurrent-breast-cancer/basics/definition/CON-20032432 . Mayo Clinic Footer Legal Conditions and ...

  4. 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.

  5. Targeting Breast Cancer Metastasis

    OpenAIRE

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various me...

  6. 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.

  7. Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal-epithelial transition and suppresses xenograft tumor growth of invasive breast cancer cells.

    Science.gov (United States)

    Bambang, I Fon; Xu, Songci; Zhou, Jianbiao; Salto-Tellez, Manuel; Sethi, Sunil K; Zhang, Daohai

    2009-11-01

    Endoplasmic reticulum protein 29 (ERp29) is a novel endoplasmic reticulum (ER) secretion factor that facilitates the transport of secretory proteins in the early secretory pathway. Recently, it was found to be overexpressed in several cancers; however, little is known regarding its function in breast cancer progression. In this study, we show that the expression of ERp29 was reduced with tumor progression in clinical specimens of breast cancer, and that overexpression of ERp29 resulted in G(0)/G(1) arrest and inhibited cell proliferation in MDA-MB-231 cells. Importantly, overexpression of ERp29 in MDA-MB-231 cells led to a phenotypic change and mesenchymal-epithelial transition (MET) characterized by cytoskeletal reorganization with loss of stress fibers, reduction of fibronectin (FN), reactivation of epithelial cell marker E-cadherin and loss of mesenchymal cell marker vimentin. Knockdown of ERp29 by shRNA in MCF-7 cells reduced E-cadherin, but increased vimentin expression. Furthermore, ERp29 overexpression in MDA-MB-231 and SKBr3 cells decreased cell migration/invasion and reduced cell transformation, whereas silencing of ERp29 in MCF-7 cells enhanced cell aggressive behavior. Significantly, expression of ERp29 in MDA-MB-231 cells suppressed tumor formation in nude mice by repressing the cell proliferative index (Ki-67 positivity). Transcriptional profiling analysis showed that ERp29 acts as a central regulator by upregulating a group of genes with tumor suppressive function, for example, E-cadherin (CDH1), cyclin-dependent kinase inhibitor (CDKN2B) and spleen tyrosine kinase (SYK), and by downregulating a group of genes that regulate cell proliferation (eg, FN, epidermal growth factor receptor (EGFR) and plasminogen activator receptor (uPAR)). It is noteworthy that ERp29 significantly attenuated the overall ERK cascade, whereas the ratio of p-ERK1 to p-ERK2 was highly increased. Taken together, our results showed that ERp29 is a novel regulator leading to cell

  8. The Reproducibility of Nuclear Morphometric Measurements in Invasive Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Pauliina Kronqvist

    1997-01-01

    Full Text Available The intraobserver and interobserver reproducibility of computerized nuclear morphometry was determined in repeated measurements of 212 samples of invasive breast cancer. The influence of biological variation and the selection of the measurement area was also tested. Morphometrically determined mean nuclear profile area (Pearson’s r 0.89, grading efficiency (GE 0.95 and standard deviation (SD of nuclear profile area (Pearson’s r 0.84, GE 0.89 showed high reproducibility. In this respect, nuclear morphometry equals with other established methods of quantitative pathology and exceeds the results of subjective grading of nuclear atypia in invasive breast cancer. A training period of eight days was sufficient to produce clear improvement in consistency of nuclear morphometry results. By estimating the sources of variation it could be shown that the variation associated with the measurement procedure itself is small. Instead, sample associated variation is responsible for the majority of variation in the measurements (82.9% in mean nuclear profile area and 65.9% in SD of nuclear profile area. This study points out that when standardized methods are applied computerized morphometry is a reproducible and reliable method of assessing nuclear atypia in invasive breast cancer. For further improvement special emphasize should be put on sampling rules of selecting the microscope fields and measurement areas.

  9. 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...... cancer overdiagnosis, and false-positive results. On the basis of the studies reviewed, the authors present a first estimate of the benefit and harm balance sheet. For every 1,000 women screened biennially from ages 50 to 51 years until ages 68 to 69 years and followed up until age 79 years, an estimated...

  10. Increasing Breast Cancer Surveillance Among African American Breast Cancer Survivors

    Science.gov (United States)

    2010-01-01

    Family history of breast cancer  specifically mother or sister diagnosed with breast cancer  Not the same as genetic risk for breast cancer...treatment. Table 5 presents sociodemographic variables for the first 20 SIS participants. The majority of participants were African American, unmarried

  11. Breast Cancer Basics and You

    Science.gov (United States)

    ... in both men and women, although male breast cancer is rare. The Breasts Inside a woman's breast are 15 to 20 sections called lobes. Each lobe contains many smaller sections called lobules. These are groups of tiny glands that make breast milk. Breast milk flows through thin tubes called ducts ...

  12. Genetics Home Reference: breast cancer

    Science.gov (United States)

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions breast cancer breast cancer Enable ...

  13. Inflammatory breast cancer: an overview

    NARCIS (Netherlands)

    Uden, D.J. van; Laarhoven, H.W.M. van; Westenberg, A.H.; Wilt, J.H. de; Blanken-Peeters, C.F.

    2015-01-01

    Inflammatory breast cancer (IBC) is the most aggressive entity of breast cancer. Management involves coordination of multidisciplinary management and usually includes neoadjuvant chemotherapy, ablative surgery if a tumor-free resection margin is expected and locoregional radiotherapy. This multimoda

  14. 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

  15. 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.

  16. 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.

  17. The impact of in situ breast cancer and family history on risk of subsequent breast cancer events and mortality - a population-based study from Sweden

    NARCIS (Netherlands)

    Sackey, Helena; Hui, Miao; Czene, Kamila; Verkooijen, Helena; Edgren, Gustaf; Frisell, Jan; Hartman, Mikael

    2016-01-01

    BACKGROUND: The clinical behavior of in situ breast cancer is incompletely understood and several factors have been associated with invasive recurrence. The purpose of this study was to evaluate long-term risk of subsequent breast cancer and mortality among women diagnosed with in situ breast cancer

  18. 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.

  19. A Novel Multi-voxel Based Quantitation of Metabolites and Lipids Non-invasively Combined with Diffusion Weighted Imaging in Breast Cancer

    Science.gov (United States)

    2011-09-01

    20. Bogner W, Gruber S, Pinker K, et al. Diffusion-weighted MR for Differentiation of Breast Lesions at 3.0 T: How Does Selection of Diffusion...Combined with Diffusion Weighted Imaging in Breast Cancer M. Albert Thomas, Neil Wilson, Jon Furuyama, Nanette DeBruhl and Lawrence Bassett Radiological

  20. Affluence and Breast Cancer.

    Science.gov (United States)

    Lehrer, Steven; Green, Sheryl; Rosenzweig, Kenneth E

    2016-09-01

    High income, high socioeconomic status, and affluence increase breast cancer incidence. Socioeconomic status in USA breast cancer studies has been assessed by block-group socioeconomic measures. A block group is a portion of a census tract with boundaries that segregate, as far as possible, socioeconomic groups. In this study, we used US Census income data instead of block groups to gauge socioeconomic status of breast cancer patients in relationship with incidence, prognostic markers, and survival. US state breast cancer incidence and mortality data are from the U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2011. Three-Year-Average Median Household Income by State, 2010 to 2012, is from the U.S. Census Bureau, Current Population Survey, 2011 to 2013 Annual Social and Economic Supplements. County incomes are from the 2005-2009 American Community Survey of the U.S. Census Bureau. The American Community Survey is an ongoing statistical survey that samples a small percentage of the population yearly. Its purpose is to provide communities the information they need to plan investments and services. Breast cancer county incidence and survival data are from the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) data base. We analyzed SEER data from 198 counties in California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, Utah, and Washington. SEER uses the Collaborative Stage (CS) Data Collection System. We have retained the SEER CS variables. There was a significant relationship of income with breast cancer incidence in 50 USA states and the District of Columbia in White women (r = 0.623, p breast cancer. Income was not correlated with 5-year survival of Black race (p = 0.364) or other races (p = 0.624). The multivariate general linear model with income as covariate, 5-year survival by race as a dependent variable, showed a significant effect of income and White race on 5-year survival (p breast cancer

  1. 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

  2. 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

  3. Primary cilia are lost in preinvasive and invasive prostate cancer.

    Directory of Open Access Journals (Sweden)

    Nadia B Hassounah

    Full Text Available Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Little is known about the role of primary cilia in preinvasive and invasive prostate cancer. However, reduced cilia expression has been observed in human cancers including pancreatic cancer, renal cell carcinoma, breast cancer, cholangiocarcinoma, and melanoma. The aim of this study was to characterize primary cilia expression in preinvasive and invasive human prostate cancer, and to investigate the correlation between primary cilia and the Wnt signaling pathway. Human prostate tissues representative of stages of prostate cancer formation (normal prostate, prostatic intraepithelial neoplasia (PIN, and invasive prostate cancer (including perineural invasion were stained for ciliary proteins. The frequency of primary cilia was determined. A decrease in the percentage of ciliated cells in PIN, invasive cancer and perineural invasion lesions was observed when compared to normal. Cilia lengths were also measured to indirectly test functionality. Cilia were shorter in PIN, cancer, and perineural invasion lesions, suggesting dysfunction. Primary cilia have been shown to suppress the Wnt pathway. Increased Wnt signaling has been implicated in prostate cancer. Therefore, we investigated a correlation between loss of primary cilia and increased Wnt signaling in normal prostate and in preinvasive and invasive prostate cancer. To investigate Wnt signaling in our cohort, serial tissue sections were stained for β-catenin as a measure of Wnt signaling. Nuclear β-catenin was analyzed and Wnt signaling was found to be higher in un-ciliated cells in the normal prostate, PIN, a subset of invasive cancers, and perineural invasion. Our results suggest that cilia normally function to suppress the Wnt signaling pathway in epithelial cells and that cilia loss may play a role in increased Wnt signaling in some prostate cancers. These results suggest that cilia are dysfunctional in human

  4. 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 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...

  5. TNM staging and classification (familial and nonfamilial of breast cancer in Jordanian females

    Directory of Open Access Journals (Sweden)

    M F Atoum

    2010-01-01

    Full Text Available Purpose : Staging of breast tumor has important implications for treatment and prognosis. This study aims at pinpointing the frequency of each stage among familial and nonfamilial breast cancers. Materials and Methods : Ninety-nine Jordanian females diagnosed with familial and nonfamilial breast cancer between 2000 and 2002 were enrolled in this study All breast cancer cases were staged according to the TNM classification into in situ, early invasive, advanced invasive and metastatic. Results : Forty-three cases were familial breast cancer and 56 were nonfamilial. One female breast cancer was diagnosed with ductal carcinoma in situ (DCIS cancer. Fifty cases were diagnosed in early stages of invasive breast cancer, of which 31 cases were familial, 29 cases were classified as advanced invasive, where 21 cases were nonfamilial and 19 cases were metastatic stage of breast cancer, with 16 nonfamilial cases. Stage 2b was the most common stage of early invasive cases and represented 48% of the early stage of breast cancer. On the other hand, among cases diagnosed with advanced invasive breast cancer, stage 3a was the most common stage and represented 89.6% of the advanced stage. Interestingly, all cases of stage 3a belonged to TNM stages of T2N2M0 and T3N1M0. The tumor size in all cases of Jordanian females diagnosed with advanced invasive breast cancer exceeded 2 cm in size due to selection bias from symptomatic women in our study. Conclusion : The incidence of nonfamilial breast cancer was slightly higher than that of the familial type amongst studied the Jordanian females studied. The early invasive stage of breast cancer was more common in the familial while the advanced invasive and metastatic breast cancer cases were encountered more often in the nonfamilial type. Our study was based on a small sample and symptomatic women. Therefore, more research with larger population samples is needed to confirm this conclusion.

  6. 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

  7. 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。

  8. Abortion, Miscarriage, and Breast Cancer Risk

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk: 2003 Workshop In ... cancer risk, including studies of induced and spontaneous abortions. They concluded that having an abortion or miscarriage ...

  9. Interstitial guidance of cancer invasion.

    NARCIS (Netherlands)

    Gritsenko, P.G.; Ilina, O.; Friedl, P.H.

    2012-01-01

    Cancer cell invasion into healthy tissues develops preferentially along pre-existing tracks of least resistance, followed by secondary tissue remodelling and destruction. The tissue scaffolds supporting or preventing guidance of invasion vary in structure and molecular composition between organs. In

  10. Early detection of breast cancer.

    Science.gov (United States)

    Nettles-Carlson, B

    1989-01-01

    Timely, comprehensive screening for breast cancer is a major, though often overlooked, component of primary health care for women. This article reviews the scientific rationale for screening and outlines the current recommendations of the American Cancer Society and the U.S. Preventive Services Task Force regarding the use of mammography, clinical breast examination (CBE), and breast self-examination (BSE). Nursing interventions to decrease barriers to effective screening are discussed, and an expanded role of nurses in breast cancer screening is proposed.

  11. Brachytherapy in breast cancer: an effective alternative

    Directory of Open Access Journals (Sweden)

    Janusz Skowronek

    2014-03-01

    Full Text Available Breast conserving surgery (BCS with following external beam radiation therapy (EBRT of the conserved breast has become widely accepted in the last decades for the treatment of early invasive breast cancer. The standard technique of EBRT after BCS is to treat the whole breast up to a total dose of 42.5 to 50 Gy. An additional dose is given to treated volume as a boost to a portion of the breast. In the early stage of breast cancer, research has shown that the area requiring radiation treatment to prevent the cancer from local recurrence is the breast tissue that surrounds the area where the initial cancer was removed. Accelerated partial breast irradiation (APBI is an approach that treats only the lumpectomy bed plus a 1-2 cm margin rather than the whole breast and as a result allows accelerated delivery of the radiation dose in four to five days. There has been a growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy (3D-EBRT and intra-operative radiation therapy (IORT. Balloon-based brachytherapy approaches include MammoSite, Axxent electronic brachytherapy, Contura, hybrid brachytherapy devices. Another indication for breast brachytherapy is reirradiation of local recurrence after mastectomy. Published results of brachytherapy are very promising. We discuss the current status, indications, and technical aspects of breast cancer brachytherapy.

  12. Breast cancer epidemiology.

    Science.gov (United States)

    Kelsey, J L; Berkowitz, G S

    1988-10-15

    The various risk factors for breast cancer have been recognized for many years. A table lists these established breast cancer risk factors together with the approximate magnitude of the increase in risk associated with them. Breast cancer incidence rates increase with age throughout the life span in Western countries, although the rate of increase is greater up to age 50 years than after 50 years. Breast cancer is more common among women in upper rather than lower social classes, among women who never have been married, among women living in urban areas, among women living in the northern US than in the southern US, and among whites than blacks, at least among those over age 50. Women in North American and Northern European countries have the highest risk for breast cancer, women in Southern European and Latin American countries are at intermediate risk, and women in Africa and Asian countries have the lowest risk. Yet, rapid rates of increase in incident rates have been noted in recent years in many Asian, Central European, and some South American countries. The later the age at which a woman has her 1st full-term pregnancy, the higher her risk for breast cancer; the earlier the age at menarche and the later the age at menopause the higher the risk; and among women who have a premenopausal oophorectomy, the earlier the age at which this occurs the lower the risk. Among postmenopausal women, obesity is associated with an increase in risk. Lactation is negatively associated with subsequent breast cancer risk. Some current research is considering potential risk factors that have not been well studied in the past, including alcohol consumption, cigarette smoking, caffeine consumption, exposure to diethylstilbestrol (DES), emotional stress, exposure to electric power, and lack of physical activity. Other areas of current research reviewed here include radiation, mammographic parenchymal patterns, a high-fat diet, use of oral contraceptives (OCs), use of estrogen

  13. 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

  14. 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.

  15. Breast Cancer in Art Painting

    OpenAIRE

    2011-01-01

    Breast cancer is an emotive cancer. It is a disease that affects a visible sexual organ and it is the commonest single cause of death of women between 40 and 60 years of age. Nevertheless, this type of cancer was infrequently depicted in art paintings. In this article the themes from the breast cancer in famous art paintings are discussed.

  16. Intracystic papillary breast cancer: a clinical update

    Science.gov (United States)

    Reefy, Sara Al; Kameshki, Rashid; Sada, Dhabya Al; Elewah, Abdullah Al; Awadhi, Arwa Al; Awadhi, Kamil Al

    2013-01-01

    Introduction: Intracystic (encysted) papillary cancer (IPC) is a rare entity of breast cancer accounting for approximately (1–2%) of all breast tumours [1], usually presenting in postmenopausal women and having an elusive natural history. The prediction of the biological behaviour of this rare form of breast cancer and the clinical outcome showed its overall favourable prognosis; however, its consideration as a form of ductal carcinoma in situ with non-invasive nature is to be reconsidered as it has been shown to present histologically with invasion of basement membrane and even metastasis [2]. The objective of this review is to shed some light on this rare, diagnostically challenging form of breast cancer, including its radiological, histological, and molecular characteristics and its pathological classification. The final goal is to optimize the clinical management including the role of sentinel lymph node biopsy (SLNB), general management with adjuvant radiotherapy (RT), mammary ductoscopy, and hormonal treatment. Methods: A literature review, facilitated by Medline, PubMed, and the Cochrane database, was carried out using the terms ‘Intracystic (encysted) papillary breast cancer’. Results: Intracystic papillary breast cancer (IPC) is best managed in the context of a multidisciplinary team. Surgical excision of the lump with margins in excess of 2 mm is considered satisfactory. Sentinel lymph node biopsy (SLNB) is recommended as data have shown the possibility of the presence of invasive cancer in the final histology. RT following IPC alone is of uncertain significance as this form of cancer is usually low grade and rarely recurs. However, if it is associated with DCIS or invasive cancer and found in young women, radiotherapy may be prudent to reduce local recurrence. Large tumours, centrally located or in cases where breast conserving surgery is unable to achieve a favourable aesthetic result, a skin sparing mastectomy with the opportunity for immediate

  17. 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.

  18. Hormones and Breast Cancer.

    Science.gov (United States)

    1997-10-01

    pathway of El metabolism may be altered by dietary (in particular, cruciferous vegetables ) and other factors (54-58). In this project we compared the... Cancer PRINCIPAL INVESTIGATOR: Giske Ursin, M.D., Ph.D. CONTRACTING ORGANIZATION: University of Southern California School of Medicine Los Angeles...TYPE AND DATES COVERED I October 1997 Final (30 Sep 94 - 29 Sep 97) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Hormones and Breast Cancer DAMD17-94-J

  19. Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

    Energy Technology Data Exchange (ETDEWEB)

    Matsunuma, Ryoichi, E-mail: r-matsunuma@nifty.com [Department of Surgery, Breast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo (Japan); First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka (Japan); Oguchi, Masahiko [Radiation Oncology Department, Breast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo (Japan); Fujikane, Tomoko [Department of Surgery, Breast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo (Japan); Matsuura, Masaaki [Bioinformatics Group, Genome Center of the Japanese Foundation for Cancer Research and Division of Cancer Genomics, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo (Japan); Sakai, Takehiko; Kimura, Kiyomi; Morizono, Hidetomo; Iijima, Kotaro; Izumori, Ayumi; Miyagi, Yumi; Nishimura, Seiichiro; Makita, Masujiro [Department of Surgery, Breast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo (Japan); Gomi, Naoya [Department of Diagnostic Imaging, Breast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo (Japan); Horii, Rie [Division of Pathology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo (Japan); Akiyama, Futoshi [Division of Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo (Japan); Iwase, Takuji [Department of Surgery, Breast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo (Japan)

    2012-07-01

    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.

  20. Breast Cancer Research Program

    Science.gov (United States)

    2010-09-01

    tion of tumor cells with red indicating the highest density of tumor cells at the primary tumor (4th mammary fat pad ) and purple/blue showing the...Idea Award Elaine Hardman and Philippe Georgel “ Maternal Consumption of Omega 3 Fatty Acids to Reduce Breast Cancer Risk in Offspring” FY09

  1. Living Beyond Breast Cancer

    Science.gov (United States)

    ... MBC Radiation Therapy for MBC Surgery for MBC Yoga and MBC Side Effects Bone Health and MBC Bone Pain and MBC ... Yoga Poses Special Situations Yoga and Lymphedema Risk Yoga and Metastatic Breast Cancer Side Effects Anemia Bone Loss Bone Pain Chemobrain Depression and ...

  2. 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.

  3. Progestins and breast cancer.

    Science.gov (United States)

    Pasqualini, Jorge R

    2007-10-01

    Progestins exert their progestational activity by binding to the progesterone receptor (form A, the most active and form B, the less active) and may also interact with other steroid receptors (androgen, glucocorticoid, mineralocorticoid, estrogen). They can have important effects in other tissues besides the endometrium, including the breast, liver, bone and brain. The biological responses of progestins cover a very large domain: lipids, carbohydrates, proteins, water and electrolyte regulation, hemostasis, fibrinolysis, and cardiovascular and immunological systems. At present, more than 200 progestin compounds have been synthesized, but the biological response could be different from one to another depending on their structure, metabolism, receptor affinity, experimental conditions, target tissue or cell line, as well as the biological response considered. There is substantial evidence that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of estradiol (E(2)) from circulating precursors. Two principal pathways are implicated in the final steps of E(2) formation in breast cancer tissue: the 'aromatase pathway', which transforms androgens into estrogens, and the 'sulfatase pathway', which converts estrone sulfate (E(1)S) into estrone (E(1)) via estrone sulfatase. The final step is the conversion of weak E(1) to the potent biologically active E(2) via reductive 17beta-hydroxysteroid dehydrogenase type 1 activity. It is also well established that steroid sulfotransferases, which convert estrogens into their sulfates, are present in breast cancer tissues. It has been demonstrated that various progestins (e.g. nomegestrol acetate, medrogestone, promegestone) as well as tibolone and their metabolites can block the enzymes involved in E(2) bioformation (sulfatase, 17beta-hydroxysteroid dehydrogenase) in breast cancer cells. These substances can also stimulate the sulfotransferase activity which converts estrogens into the biologically

  4. Induction of the mesenchymal to epithelial transition by demethylation- activated microRNA-200c is involved in the anti-migration/invasion effects of arsenic trioxide on human breast cancer cells.

    Science.gov (United States)

    Si, Lu; Jiang, Fei; Li, Yuan; Ye, Xianqing; Mu, Juan; Wang, Xingxing; Ning, Shilong; Hu, Chunyan; Li, Zhong

    2015-09-01

    Breast cancer is a major health problem worldwide. Current standard practices for treatment of breast cancer are less than satisfactory because of high rates of metastasis. Arsenic trioxide (As(2)O(3)), which induces demethylation of DNA and causes apoptosis, has been used as an anti-tumor agent. Little is known, however, regarding its anti-metastatic effects. The microRNA-200c (miR-200c), which is frequently lowly expressed in triple negative breast cancers (TNBCs), inhibits metastasis by inducing the mesenchymal to epithelial transition (MET). Here, we report that As(2)O(3) attenuates the migratory and invasive capacities of breast cancer cells, MDA-MB-231 and BT-549. Notably, As(2)O(3) induces an MET in vitro and in vivo, as determined by the increased expression of the epithelial marker, E-cadherin and decreased expressions of mesenchymal markers, N-cadherin and vimentin. Moreover, As(2)O(3) up-regulates the expression of miR-200c through demethylation. Over-expression of miR-200c enhances the expression of E-cadherin and decreases the expressions of N-cadherin and vimentin. Further, in MDA-MB-231 cells exposed to As(2)O(3), knockdown of miR-200c blocks the As(2)O(3) -induced MET. Finally, in MDA-MB-231 and BT-549 cells exposed to As(2)O(3), knockdown of miR-200c decreases the As(2)O(3) -induced inhibition of the migratory and invasive capacities. By identifying a mechanism whereby As(2)O(3) regulates miR-200c and MET, the results establish the anti-migration/invasion potential of arsenic trioxide.

  5. Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

    Science.gov (United States)

    2017-03-21

    Cancer Survivor; Early-Stage Breast Carcinoma; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  6. 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.

  7. The contribution of risk factors to the higher incidence of invasive and in situ breast cancers in women with higher levels of education in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    G. Menvielle (Gwenn); A.E. Kunst (Anton); C.H. van Gils (Carla); P.H.M. Peeters (Petra); H.C. Boshuizen (Hendriek); K. Overvad (Kim); A. Olsen (Anja); A. Tjonneland (Anne); S. Hermann (Silke); R. Kaaks (Rudolf); M.M. Bergmann (Manuela); A.-K. Illner (Anne-Kathrin); P. Lagiou (Pagona); D. Trichopoulos (Dimitrios); A. Trichopoulou (Antonia); D. Palli (Domenico); F. Berrino (Franco); A. Mattiello (Amelia); R. Tumino (Rosario); C. Sacerdote (Carlotta); A.M. May (Anne); E. Monninkhof (Evelyn); T. Braaten (Tonje); E. Lund (Eiliv); J.R. Quirós; E.J. Duell (Eric); M.J. Sánchez; C. Navarro (Carmen); S. Borgquist (Signe); J. Manjer (Jonas); K-T. Khaw (Kay-Tee); G.K. Reeves (Gillian); V. Chajes (Véronique); S. Rinaldi (Sabina); N. Slimani (Nadia); V. Gallo (Valentina); P. Vineis (Paolo); E. Riboli (Elio); H.B. Bueno-De-Mesquita (Bas); N.E. Allen (Naomi); E. Ardanaz (Eva)

    2011-01-01

    textabstractThe authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasi

  8. 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...

  9. Estimation of health state utilities in breast cancer

    Directory of Open Access Journals (Sweden)

    Kim SH

    2017-03-01

    Full Text Available Seon-Ha Kim,1 Min-Woo Jo,2 Minsu Ock,2 Hyeon-Jeong Lee,2 Jong-Won Lee3,4 1Department of Nursing, College of Nursing, Dankook University, Cheonan, 2Department of Preventive Medicine, University of Ulsan College of Medicine, Seoul, 3Department of Breast and Endocrine Surgery, Asan Medical Center, Seoul, 4Department of Surgery, University of Ulsan College of Medicine, Seoul, South Korea Purpose: The aim of this study is to determine the utility of breast cancer health states using the standard gamble (SG and visual analog scale (VAS methods in the Korean general population.Materials and methods: Eight hypothetical breast cancer health states were developed based on patient education material and previous publications. Data from 509 individuals from the Korean general population were used to evaluate breast cancer health states using the VAS and the SG methods, which were obtained via computer-assisted personal interviews. Mean utility values were calculated for each human papillomavirus (HPV-related health state.Results: The rank of health states was identical between two valuation methods. SG values were higher than VAS values in all health states. The utility values derived from SG were 0.801 (noninvasive breast cancer with mastectomy and followed by reconstruction, 0.790 (noninvasive breast cancer with mastectomy only, 0.779 (noninvasive breast cancer with breast-conserving surgery and radiation therapy, 0.731 (invasive breast cancer with surgery, radiation therapy, and/or chemotherapy, 0.610 (locally advanced breast cancer with radical mastectomy with radiation therapy, 0.587 (inoperable locally advanced breast cancer, 0.496 (loco-regional recurrent breast cancer, and 0.352 (metastatic breast cancer.Conclusion: Our findings might be useful for economic evaluation of breast cancer screening and interventions in general populations. Keywords: breast neoplasm, Korea, quality-adjusted life years, quality of life

  10. Breast cancer associated with type 1 neurofibromatosis.

    Science.gov (United States)

    Salemis, Nikolaos S; Nakos, Georgios; Sambaziotis, Dimitrios; Gourgiotis, Stavros

    2010-10-01

    The association between breast cancer and type 1 neurofibromatosis (NF1) is a rare clinical entity. We herein present the case of a 59-year-old woman, with typical clinical manifestations of NF1, who presented with a painless lump in her right breast, which she had first noticed 8 months earlier. Clinical examination and diagnostic workup were suggestive of a breast carcinoma, and a modified radical mastectomy was performed. Histopathological examination revealed a poorly differentiated invasive ductal breast carcinoma and multiple neurofibromas. The pathological staging was pT2N1a according to TNM/UICC. Delayed presentation of the patient was the result of her mistakenly identifying the breast tumor as a manifestation of NF1 neurofibromatosis.

  11. 14-3-3σ Expression Identifies Basal-Like Breast Cancer and Regulates Tumor Invasion by Defining Subcellular Regions of Actin Polymerization

    OpenAIRE

    Boudreau, Aaron Thomas

    2010-01-01

    The mammary gland can be thought of as an "organism" with very complicated biology. The normal breast is comprised of a milieu of different cell types and extracellular matrix (ECM) components, the sum of which yield a complex microenvironment and series of biological interactions that are essential for normal development and functional differentiation. Many of these events go awry in breast cancer, a disease best characterized by the loss of tissue structure, morphology, and function - in es...

  12. 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.

  13. GATA3 Inhibits Breast Cancer Metastasis through the Reversal of Epithelial-Mesenchymal Transition*

    OpenAIRE

    Yan, Wei; Cao, Qing Jackie; Arenas, Richard B.; Bentley, Brooke; Shao, Rong

    2010-01-01

    GATA3, a transcription factor that regulates T lymphocyte differentiation and maturation, is exclusively expressed in early stage well differentiated breast cancers but not in advanced invasive cancers. However, little is understood regarding its activity and the mechanisms underlying this differential expression in cancers. Here, we employed GATA3-positive, non-invasive (MCF-7) and GATA3-negative, invasive (MDA-MB-231) breast cancer cells to define its role in the transformation between thes...

  14. 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.

  15. Treatment Option Overview (Male Breast Cancer)

    Science.gov (United States)

    ... Cancers Breast Cancer Screening Research Male Breast Cancer Treatment (PDQ®)–Patient Version General Information about Male Breast ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  16. You, Your Teenage Daughter and Breast Cancer.

    Science.gov (United States)

    Brateman, Libby

    1991-01-01

    Discusses breast cancer and teenagers, focusing on how parents can introduce the subject and encourage breast self-examination. The article provides information on breast cancer statistics, mammography, and American Cancer Society services. (SM)

  17. Braving Breast Cancer: Just Do It!

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Breast Cancer Braving Breast Cancer: Just Do It! Past Issues / Spring - Summer 2010 Table of Contents Breast cancer survivor Jana Brightwell, pictured here on the NIH ...

  18. Breast cancer fear in African American breast cancer survivors.

    Science.gov (United States)

    Gibson, Lynette M; Thomas, Sheila; Parker, Veronica; Mayo, Rachel; Wetsel, Margaret Ann

    2014-01-01

    The purpose of this study was to describe breast cancer fear according to phase of survivorship, determine whether breast cancer fear levels differed among survivorship phases, and determine the relationship between fear and age in African-American breast cancer survivors. The study utilized secondary data analysis from the study, Inner Resources as Predictors of Psychological Well-Being in AABCS. A new subscale entitled, "Breast Cancer Fear" was adapted from the Psychological Well Being Subscale by Ferrell and Grant. There was no significant difference between fear and phase of survivorship. There was a significant positive relationship between age and fear.

  19. Cell Polarity Proteins in Breast Cancer Progression.

    Science.gov (United States)

    Rejon, Carlis; Al-Masri, Maia; McCaffrey, Luke

    2016-10-01

    Breast cancer, one of the leading causes of cancer related death in women worldwide, is a heterogeneous disease with diverse subtypes that have different properties and prognoses. The developing mammary gland is a highly proliferative and invasive tissue, and some of the developmental programs may be aberrantly activated to promote breast cancer progression. In the breast, luminal epithelial cells exhibit apical-basal polarity, and the failure to maintain this organizational structure, due to disruption of polarity complexes, is implicated in promoting hyperplasia and tumors. Therefore, understanding the mechanisms underlying loss of polarity will contribute to our knowledge of the early stages leading to the pathogenesis of the disease. In this review, we will discuss recent findings that support the idea that loss of apical-basal cell polarity is a crucial step in the acquisition of the malignant phenotype. Oncogene induced loss of tissue organization shares a conserved cellular mechanism with developmental process, we will further describe the role of the individual polarity complexes, the Par, Crumbs, and Scribble, to couple cell division orientation and cell growth. We will examine symmetric or asymmetric cell divisions in mammary stem cell and their contribution to the development of breast cancer subtypes and cancer stem cells. Finally, we will highlight some of the recent advances in our understanding of the molecular mechanisms by which changes in epithelial polarity programs promote invasion and metastasis through single cell and collective cell modes. J. Cell. Biochem. 117: 2215-2223, 2016. © 2016 Wiley Periodicals, Inc.

  20. Getting free of breast cancer

    DEFF Research Database (Denmark)

    Halttunen, Arja; Hietanen, P; Jallinoja, P

    1992-01-01

    Twenty-two breast cancer patients who were relapse-free and had no need for cancer-related treatment were interviewed 8 years after mastectomy in order to evaluate their feelings of getting free of breast cancer and the meaning of breast cancer in their lives. The study is a part of an intervention...... and follow-up study of 57 breast cancer patients. Half of the 22 patients still had frequent or occasional thoughts of recurrence and over two-thirds still thought they had not been 'cured' of cancer. More than half of the patients admitted that going through breast cancer had made them more mature. Women...... who had less thoughts of recurrence belonged to a group that had gone through an eight-week group psychotherapy intervention, were less depressed and had more other illnesses. Women who felt 'cured' had less limitations and restrictions due to cancer and belonged more often to higher social classes...

  1. 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

  2. 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.

  3. The Breast Cancer DNA Interactome

    Science.gov (United States)

    2014-12-01

    Sugumar A, Liu YC, Xia Q , Koh YS, Matsuo K. Insulin-like growth factor (IGF)-I and IGF-binding protein 3 and the risk of premenopausal breast cancer: a...stimulates autophagy and promotes the survival of breast cancer cells exposed to adverse microenvironments. Oncogene 32(19): 2412 2420. 29. Mehta HH, Gao Q ...Award Number: W81XWH-11-1-0474 TITLE: The Breast Cancer DNA Interactome PRINCIPAL INVESTIGATOR: Andrew R. Hoffman CONTRACTING ORGANIZATION

  4. Progress in breast cancer: overview.

    Science.gov (United States)

    Arteaga, Carlos L

    2013-12-01

    This edition of CCR Focus titled Research in Breast Cancer: Frontiers in Genomics, Biology, and Clinical Investigation reviews six topics that cover areas of translational research of high impact in breast cancer. These topics represent areas of breast cancer research where significant progress has occurred but also where very important challenges remain. The papers in this CCR Focus section are contributed by experts in the respective areas of investigation. Herein, key aspects of these contributions and the research directions they propose are reviewed.

  5. 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.

  6. 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

    3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor......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...

  7. 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

    3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P = 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor......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...

  8. Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jie [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Yang, Xi-fei [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Ren, Xiao-hu [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Meng, Xiao-jing [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Huang, Hai-yan [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zhao, Qiong-hui [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen (China); Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Liu, Jian-jun, E-mail: bio-research@hotmail.com [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zou, Fei, E-mail: zoufei616@163.com [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China)

    2014-10-10

    Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.

  9. A systematic review of bevacizumab efficacy in breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Grummedal Christiansen, Ole; 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...

  10. An Analytical Approach Differentiates Between Individual and Collective Cancer Invasion

    Directory of Open Access Journals (Sweden)

    Elad Katz

    2011-01-01

    Full Text Available Tumour cells employ a variety of mechanisms to invade their environment and to form metastases. An important property is the ability of tumour cells to transition between individual cell invasive mode and collective mode. The switch from collective to individual cell invasion in the breast was shown recently to determine site of subsequent metastasis. Previous studies have suggested a range of invasion modes from single cells to large clusters. Here, we use a novel image analysis method to quantify and categorise invasion. We have developed a process using automated imaging for data collection, unsupervised morphological examination of breast cancer invasion using cognition network technology (CNT to determine how many patterns of invasion can be reliably discriminated. We used Bayesian network analysis to probabilistically connect morphological variables and therefore determine that two categories of invasion are clearly distinct from one another. The Bayesian network separated individual and collective invading cell groups based on the morphological measurements, with the level of cell-cell contact the most discriminating morphological feature. Smaller invading groups were typified by smoother cellular surfaces than those invading collectively in larger groups. Interestingly, elongation was evident in all invading cell groups and was not a specific feature of single cell invasion as a surrogate of epithelial-mesenchymal transition. In conclusion, the combination of cognition network technology and Bayesian network analysis provides an insight into morphological variables associated with transition of cancer cells between invasion modes. We show that only two morphologically distinct modes of invasion exist.

  11. Targeting Master Regulators of the Breast Cancer Metastasis Transcriptome

    Science.gov (United States)

    2014-07-01

    rigorous state -of-the- art bioinformatic analysis, and functional models using isogenic human breast cancer cells with varying metastatic potential, we will...A, Ergun B, Erbersdobler A, Jung K, Stephan C. RECK overexpression decreases invasive potential in prostate cancer cells. Prostate 2012; 72: 948–954...Breast Cancer Metastasis Transcriptome PRINCIPAL INVESTIGATOR: Timothy A. Chan MD, PhD CONTRACTING ORGANIZATION: Sloan-Kettering Institute

  12. 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.

  13. 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.

  14. Role of cyclooxygenase-2 in breast cancer.

    Science.gov (United States)

    Singh, Balraj; Lucci, Anthony

    2002-11-01

    Cyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid to prostaglandin H2, is expressed in normal brain and kidney, activated macrophages, synoviocytes during inflammation, and malignant epithelial cells. COX-2 expression is stimulated by a number of inflammatory cytokines, growth factors, oncogenes, lipopolysaccharides, and tumor promoters. There is evidence that COX-2 plays a key role in tumorigenesis through stimulating epithelial cell proliferation, inhibiting apoptosis, stimulating angiogenesis, enhancing cell invasiveness, mediating immune suppression, and by increasing the production of mutagens. Results of several studies using mouse models of colon cancer and the results of clinical trials have shown COX-2 to be a useful target for the prevention and treatment of colon cancer. Studies with several other epithelial cancers involving different organ sites, e.g., breast, prostate, bladder, lung, and pancreas, suggest that COX-2 plays an important role in the pathogenesis of these cancers. In this review, we summarize the studies that pertain to the involvement of COX-2 in breast cancer. COX-2 overexpression affects the physiological processes at different organ sites in a similar manner, although specific effectors and targets of COX-2 may differ at different sites. Thus in reviewing the data on the involvement of COX-2 in breast cancer, we have also considered the findings regarding the role of COX-2 in other organ sites. Studies from mouse models of mammary tumorigenesis and from human breast cancer cell lines provide evidence that COX-2 overexpression plays an important role in the pathogenesis of malignant breast cancer in humans. Because of availability of effective and relatively safe COX-2 inhibitors, it should be soon possible to evaluate their effectiveness in the clinic for the prevention and treatment of breast cancer. It is likely that the COX-2 inhibitors will be effective in the treatment regimens involving combination

  15. Breast cancer imaging; Bildgebende Diagnostik des Mammakarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Funke, M. [Stadtklinik Baden-Baden, Brustzentrum Klinikum Mittelbaden, Radiologische Klinik, Baden-Baden (Germany); Villena, C. [Stadtklinik Baden-Baden, Brustzentrum Klinikum Mittelbaden, Frauenklinik, Baden-Baden (Germany)

    2008-06-15

    Advances in female breast imaging have substantially influenced the diagnosis, therapy, and prognosis of breast cancer in the past few years. Mammography using conventional or digital technique is considered the gold standard for the early detection of breast cancer. Other modalities such as breast ultrasound and contrast-enhanced magnetic resonance imaging of the breast play an important role in diagnostic imaging, staging, and follow-up of breast cancer. Percutaneous needle biopsy is a faster, less invasive, and more cost-effective method than surgical biopsy for verifying the histological diagnosis. New methods such as breast tomosynthesis, contrast-enhanced mammography, and positron emission tomography promise to further improve breast imaging. Further studies are mandatory to adapt these new methods to clinical needs and to evaluate their performance in clinical practice. (orig.) [German] Die Fortschritte bei den bildgebenden Verfahren der weiblichen Brust haben in den letzten Jahren die Diagnostik, die Therapie und die Prognose des Mammakarzinoms erheblich beeinflusst. Die Frueherkennungsmammographie in traditioneller oder digitaler Technik gilt heute als der ''Goldstandard'' fuer die fruehzeitige Detektion von Brustkrebs. Weitere Modalitaeten wie die Mammasonographie und die kontrastmittelgestuetzte MR-Mammographie spielen bei der bildgebenden Diagnostik, im Staging sowie in der Nachsorge des Mammakarzinoms eine wichtige Rolle. Die perkutane Nadelbiopsie stellt eine schnellere, weniger invasive und kostenguenstigere Methode dar als die diagnostische Exzision fuer die histologische Sicherung der Diagnose. Neue Modalitaeten wie Tomosynthese der Brust, kontrastverstaerkte Mammographie und Positronenemissionstomographie erheben den Anspruch, zu einer weiteren Verbesserung der Bildgebung beizutragen. Weitere Studien sind notwendig, um diese neuen Methoden an die klinischen Beduerfnisse zu adaptieren und ihren Stellenwert im klinischen Alltag

  16. Breast cancer risk factors

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2015-09-01

    Full Text Available Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women’s ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual’s life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence.

  17. Interventional MRI of the breast: minimally invasive therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hall-Craggs, M.A. [MR Unit, Middlesex Hospital, London (United Kingdom)

    2000-01-01

    In recent years a variety of minimally invasive therapies have been applied to the treatment of breast lesions. These therapies include thermal treatments (interstitial laser coagulation, focused ultrasound, radiofrequency and cryotherapy), percutaneous excision, and interstitial radiotherapy. Magnetic resonance has been used in these treatments to visualize lesions before, during and after therapy and to guide interventions. ''Temperature-sensitive'' sequences have shown changes with thermal ablation which broadly correlate with areas of tumour necrosis. Consequently, MR has the potential to monitor treatment at the time of therapy. To date, experience in the treatment of breast cancer has been restricted to small studies. Large controlled studies are required to validate the efficacy and safety of these therapies in malignant disease. (orig.)

  18. Cost-effectiveness of non-invasive assessment in the Dutch breast cancer screening program versus usual care: A randomized controlled trial

    NARCIS (Netherlands)

    Timmers, J.M.H.; Damen, J.A.A.G.; Pijnappel, R.M.; Verbeek, A.L.M.; H