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  1. 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.

  2. Epithelial-mesenchymal transition in breast cancer progression and metastasis

    Institute of Scientific and Technical Information of China (English)

    Yifan Wang; Binhua P. Zhou

    2011-01-01

    Breast cancer is the most common cancer in women,and approximately 90% of breast cancer deaths are caused by local invasion and distant metastasis of tumor cells.Epithelial-mesenchymal transition (EMT) is a vital process for large-scale cell movement during morphogenesis at the time of embryonic development.Tumor cells usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis.Several transcription factors and signals are involved in these events.In this review,we summarize recent advances in breast cancer researches that have provided new insights in the molecular mechanisms underlying EMT regulation during breast cancer progression and metastasis.We especially focus on the molecular pathways that control EMT.

  3. Integrin Signaling in Mammary Epithelial Cells and Breast Cancer

    OpenAIRE

    Lambert, Arthur W.; Sait Ozturk; Sam Thiagalingam

    2012-01-01

    Cells sense and respond to the extracellular matrix (ECM) by way of integrin receptors, which facilitate cell adhesion and intracellular signaling. Advances in understanding the mammary epithelial cell hierarchy are converging with new developments that reveal how integrins regulate the normal mammary gland. But in breast cancer, integrin signaling contributes to the development and progression of tumors. This paper highlights recent studies which examine the role of integrin signaling in mam...

  4. Differential expression of bitter taste receptors in non-cancerous breast epithelial and breast cancer cells.

    Science.gov (United States)

    Singh, Nisha; Chakraborty, Raja; Bhullar, Rajinder Pal; Chelikani, Prashen

    2014-04-04

    The human bitter taste receptors (T2Rs) are chemosensory receptors that belong to the G protein-coupled receptor superfamily. T2Rs are present on the surface of oral and many extra-oral cells. In humans 25 T2Rs are present, and these are activated by hundreds of chemical molecules of diverse structure. Previous studies have shown that many bitter compounds including chloroquine, quinidine, bitter melon extract and cucurbitacins B and E inhibit tumor growth and induce apoptosis in cancer cells. However, the existence of T2Rs in cancer cell is not yet elucidated. In this report using quantitative (q)-PCR and flow cytometry, we characterized the expression of T2R1, T2R4, T2R10, T2R38 and T2R49 in the highly metastatic breast cancer cell line MDA-MB-231, poorly metastatic cell line MCF-7, and non-cancerous mammary epithelial cell line MCF-10A. Among the 5 T2Rs analyzed by qPCR and flow cytometry, T2R4 is expressed at 40-70% in mammary epithelial cells in comparison to commonly used breast cancer marker proteins, estrogen receptor and E-cadherin. Interestingly, the expression of T2R4 was downregulated in breast cancer cells. An increase in intracellular calcium mobilization was observed after the application of bitter agonists, quinine, dextromethorphan, and phenylthiocarbamide that are specific for some of the 5 T2Rs. This suggests that the endogenous T2Rs expressed in these cells are functional. Taken together, our novel findings suggest that T2Rs are differentially expressed in mammary epithelial cells, with some T2Rs downregulated in breast cancer cells.

  5. 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

  6. Benzyl Isothiocyanate Inhibits Epithelial-Mesenchymal Transition in Cultured and Xenografted Human Breast Cancer Cells

    OpenAIRE

    Sehrawat, Anuradha; Singh, Shivendra V.

    2011-01-01

    We showed previously that cruciferous vegetable constituent benzyl isothiocyanate (BITC) inhibits growth of cultured and xenografted human breast cancer cells, and suppresses mammary cancer development in a transgenic mouse model. We now demonstrate, for the first time, that BITC inhibits epithelial-to-mesenchymal transition (EMT) in human breast cancer cells. Exposure of estrogen-independent MDA-MB-231 and estrogen-responsive MCF-7 human breast cancer cell lines and a pancreatic cancer cell ...

  7. Epithelial cell identity in hyperplastic precursors of breast cancer

    Institute of Scientific and Technical Information of China (English)

    Danila Coradini; Patrizia Boracchi; Saro Oriana; Elia Biganzoli; Federico Ambrogi

    2015-01-01

    Introduction:In the adult human breast, hyperplastic enlarged lobular unit (HELU) and atypical ductal hyperplasia (ADH) are two common abnormalities that frequently coexist with ductal carcinoma in situ (DCIS). For this reason, they have been proposed as the early steps in a biological continuum toward breast cancer. Methods:We investigated in silico the expression of 369 genes experimentally recognized as involved in establishing and maintaining epithelial cell identity and mammary gland remodeling, in HELUs or ADHs with respect to the corresponding patient-matched normal tissue. Results:Despite the common luminal origin, HELUs and ADHs proved to be characterized by distinct gene profiles that overlap for 5 genes only. While HELUs were associated with the overexpression of progesterone receptor (PGR), ADHs were characterized by the overexpression of estrogen receptor 1 (ESR1) coupled with the overexpression of some proliferation-associated genes. Conclusions:This unexpected finding contradicts the notion that in differentiated luminal cells the expression of estrogen receptor (ER) is dissociated from cell proliferation and suggests that the establishing of an ER-dependent signaling is able to sustain cell proliferation in an autocrine manner as an early event in tumor initiation. Although clinical evidence indicates that only a fraction of HELUs and ADHs evolve to invasive cancer, present findings warn that exposure to synthetic progestins, frequently administered as hormone-replacement therapy, and estrogens, when abnormally produced by adipose cells and persistently present in the stroma surrounding the mammary gland, may cause these hyperplastic lesions.

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

    DEFF Research Database (Denmark)

    Vaapil, Marica; Helczynska, Karolina; Villadsen, René

    2012-01-01

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

  9. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

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    Magnusson Magnus K

    2010-07-01

    Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

  10. An in vitro model that recapitulates the epithelial to mesenchymal transition (EMT in human breast cancer.

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    Elad Katz

    Full Text Available The epithelial to mesenchymal transition (EMT is a developmental program in which epithelial cells down-regulate their cell-cell junctions, acquire spindle cell morphology and exhibit cellular motility. In human breast cancer, invasion into surrounding tissue is the first step in metastatic progression. Here, we devised an in vitro model using selected cell lines, which recapitulates many features of EMT as observed in human breast cancer. By comparing the gene expression profiles of claudin-low breast cancers with the experimental model, we identified a 9-gene signature characteristic of EMT. This signature was found to distinguish a series of breast cancer cell lines that have demonstrable, classical EMT hallmarks, including loss of E-cadherin protein and acquisition of N-cadherin and vimentin expression. We subsequently developed a three-dimensional model to recapitulate the process of EMT with these cell lines. The cells maintain epithelial morphology when encapsulated in a reconstituted basement membrane, but undergo spontaneous EMT and invade into surrounding collagen in the absence of exogenous cues. Collectively, this model of EMT in vitro reveals the behaviour of breast cancer cells beyond the basement membrane breach and recapitulates the in vivo context for further investigation into EMT and drugs that may interfere with it.

  11. Lentiviral Vector Mediated Claudin1 Silencing Inhibits Epithelial to Mesenchymal Transition in Breast Cancer Cells

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    Xianqi Zhao

    2015-06-01

    Full Text Available Breast cancer has a high incidence and mortality rate worldwide. Several viral vectors including lentiviral, adenoviral and adeno-associated viral vectors have been used in gene therapy for various forms of human cancer, and have shown promising effects in controlling tumor development. Claudin1 (CLDN1 is a member of the tetraspan transmembrane protein family that plays a major role in tight junctions and is associated with tumor metastasis. However, the role of CLDN1 in breast cancer is largely unexplored. In this study, we tested the therapeutic potential of silencing CLDN1 expression in two breast cancer (MDA-MB-231 and MCF7 cell lines using lentiviral vector mediated RNA interference. We found that a CLDN1 short hairpin (shRNA construct efficiently silenced CLDN1 expression in both breast cancer cell lines, and CLDN1 knockdown resulted in reduced cell proliferation, survival, migration and invasion. Furthermore, silencing CLDN1 inhibited epithelial to mesenchymal transition (EMT by upregulating the epithelial cell marker, E-cadherin, and downregulating mesenchymal markers, smooth muscle cell alpha-actin (SMA and Snai2. Our data demonstrated that lentiviral vector mediated CLDN1 RNA interference has great potential in breast cancer gene therapy by inhibiting EMT and controlling tumor cell growth.

  12. Identification of 5 novel genes methylated in breast and other epithelial cancers

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    Ward Robyn L

    2010-03-01

    Full Text Available Abstract Background There are several high throughput approaches to identify methylated genes in cancer. We utilized one such recently developed approach, MIRA (methylated-CpG island recovery assay combined with CpG island arrays to identify novel genes that are epigenetically inactivated in breast cancer. Results Using this approach we identified numerous CpG islands that demonstrated aberrant DNA methylation in breast cancer cell lines. Using a combination of COBRA and sequencing of bisulphite modified DNA, we confirmed 5 novel genes frequently methylated in breast tumours; EMILIN2, SALL1, DBC1, FBLN2 and CIDE-A. Methylation frequencies ranged from between 25% and 63% in primary breast tumours, whilst matched normal breast tissue DNA was either unmethylated or demonstrated a much lower frequency of methylation compared to malignant breast tissue DNA. Furthermore expression of the above 5 genes was shown to be restored following treatment with a demethylating agent in methylated breast cancer cell lines. We have expanded this analysis across three other common epithelial cancers (lung, colorectal, prostate. We demonstrate that the above genes show varying levels of methylation in these cancers. Lastly and most importantly methylation of EMILIN2 was associated with poorer clinical outcome in breast cancer and was strongly associated with estrogen receptor as well as progesterone receptor positive breast cancers. Conclusion The combination of the MIRA assay with CpG island arrays is a very useful technique for identifying epigenetically inactivated genes in cancer genomes and can provide molecular markers for early cancer diagnosis, prognosis and epigenetic therapy.

  13. GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition.

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

    2010-04-30

    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 these two distinct phenotypes. Ectopic expression of GATA3 in MDA-MB-231 cells led to a cuboidal-like epithelial phenotype and reduced cell invasive activity. These cells also increased E-cadherin expression but decreased levels of vimentin, N-cadherin, and MMP-9. Further, MDA-MB-231 cells expressing GATA3 grew smaller primary tumors without metastasis compared with larger metastatic tumors derived from control MDA-MB-231 cells in xenografted mice. GATA3 was found to induce E-cadherin expression through binding GATA-like motifs located in the E-cadherin promoter. Blockade of GATA3 using small interfering RNA gene knockdown in MCF-7 cells triggered fibroblastic transformation and cell invasion, resulting in distant metastasis. Studies of human breast cancer showed that GATA3 expression correlated with elevated E-cadherin levels, ER expression, and long disease-free survival. These data suggest that GATA3 drives invasive breast cancer cells to undergo the reversal of epithelial-mesenchymal transition, leading to the suppression of cancer metastasis.

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

    Directory of Open Access Journals (Sweden)

    Marica Vaapil

    Full Text Available INTRODUCTION: Solid tumors are less oxygenated than their tissue of origin. Low intra-tumor oxygen levels are associated with worse outcome, increased metastatic potential and immature phenotype in breast cancer. We have reported that tumor hypoxia correlates to low differentiation status in breast cancer. Less is known about effects of hypoxia on non-malignant cells. Here we address whether hypoxia influences the differentiation stage of non-malignant breast epithelial cells and potentially have bearing on early stages of tumorigenesis. METHODS: Normal human primary breast epithelial cells and immortalized non-malignant mammary epithelial MCF-10A cells were grown in a three-dimensional overlay culture on laminin-rich extracellular matrix for up to 21 days at normoxic or hypoxic conditions. Acinar morphogenesis and expression of markers of epithelial differentiation and cell polarization were analyzed by immunofluorescence, immunohistochemistry, qPCR and immunoblot. RESULTS: In large ductal carcinoma in situ patient-specimens, we find that epithelial cells with high HIF-1α levels and multiple cell layers away from the vasculature are immature compared to well-oxygenated cells. We show that hypoxic conditions impaired acinar morphogenesis of primary and immortalized breast epithelial cells grown ex vivo on laminin-rich matrix. Normoxic cultures formed polarized acini-like spheres with the anticipated distribution of marker proteins associated with mammary epithelial polarization e.g. α6-integrin, laminin 5 and Human Milk Fat Globule/MUC1. At hypoxia, cells were not polarized and the sub-cellular distribution pattern of the marker proteins rather resembled that reported in vivo in breast cancer. The hypoxic cells remained in a mitotic state, whereas proliferation ceased with acinar morphogenesis at normoxia. We found induced expression of the differentiation repressor ID1 in the undifferentiated hypoxic MCF-10A cell structures. Acinar

  15. CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer.

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    Bergamaschi, Anna; Kim, Young H; Kwei, Kevin A; La Choi, Yoon; Bocanegra, Melanie; Langerød, Anita; Han, Wonshik; Noh, Dong-Young; Huntsman, David G; Jeffrey, Stefanie S; Børresen-Dale, Anne-Lise; Pollack, Jonathan R

    2008-12-01

    Breast cancer exhibits clinical and molecular heterogeneity, where expression profiling studies have identified five major molecular subtypes. The basal-like subtype, expressing basal epithelial markers and negative for estrogen receptor (ER), progesterone receptor (PR) and HER2, is associated with higher overall levels of DNA copy number alteration (CNA), specific CNAs (like gain on chromosome 10p), and poor prognosis. Discovering the molecular genetic basis of tumor subtypes may provide new opportunities for therapy. To identify the driver oncogene on 10p associated with basal-like tumors, we analyzed genomic profiles of 172 breast carcinomas. The smallest shared region of gain spanned just seven genes at 10p13, including calcium/calmodulin-dependent protein kinase ID (CAMK1D), functioning in intracellular signaling but not previously linked to cancer. By microarray, CAMK1D was overexpressed when amplified, and by immunohistochemistry exhibited elevated expression in invasive carcinomas compared to carcinoma in situ. Engineered overexpression of CAMK1D in non-tumorigenic breast epithelial cells led to increased cell proliferation, and molecular and phenotypic alterations indicative of epithelial-mesenchymal transition (EMT), including loss of cell-cell adhesions and increased cell migration and invasion. Our findings identify CAMK1D as a novel amplified oncogene linked to EMT in breast cancer, and as a potential therapeutic target with particular relevance to clinically unfavorable basal-like tumors.

  16. SLUG: Critical regulator of epithelial cell identity in breast development and cancer.

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    Phillips, Sarah; Kuperwasser, Charlotte

    2014-01-01

    SLUG, a member of the SNAIL family of transcriptional repressors, is known to play a diverse number of roles in the cell, and its deregulation has been observed in a variety of cancers including breast. Here, we focus on SLUG's role as a master regulator of mammary epithelial cell (MEC) fate and lineage commitment in the normal mammary gland, and discuss how aberrant SLUG expression can influence breast tumor formation, phenotype, and progression. Specifically, we discuss SLUG's involvement in MEC differentiation, stemness, cellular plasticity, and the epithelial to mesenchymal transition (EMT), and highlight the complex connection between these programs during development and disease progression. Undoubtedly, delineating how molecular factors influence lineage identity and cell-state dynamics in the normal mammary gland will contribute to our understanding of breast tumor heterogeneity.

  17. miR-506 regulates epithelial mesenchymal transition in breast cancer cell lines.

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    Arora, Himanshu; Qureshi, Rehana; Park, Woong-Yang

    2013-01-01

    Epithelial-mesenchymal transition (EMT) is an important parameter related to breast cancer survival. Among several microRNAs predicted to target EMT-related genes, miR-506 is a novel miRNA found to be significantly related to breast cancer patient survival in a meta-analysis. miR-506 suppressed the expression of mesenchymal genes such as Vimentin, Snai2, and CD151 in MDA-MB-231 human breast cancer cell line. Moreover, NF-κB bound to the upstream promoter region of miR-506 to suppress transcription. Overexpression of miR-506 inhibited TGFβ-induced EMT and suppressed adhesion, invasion, and migration of MDA-MB-231 cells. From these results, we concluded that miR-506 plays a key role in the process of EMT through posttranslational control of EMT-related genes.

  18. miR-506 regulates epithelial mesenchymal transition in breast cancer cell lines.

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    Himanshu Arora

    Full Text Available Epithelial-mesenchymal transition (EMT is an important parameter related to breast cancer survival. Among several microRNAs predicted to target EMT-related genes, miR-506 is a novel miRNA found to be significantly related to breast cancer patient survival in a meta-analysis. miR-506 suppressed the expression of mesenchymal genes such as Vimentin, Snai2, and CD151 in MDA-MB-231 human breast cancer cell line. Moreover, NF-κB bound to the upstream promoter region of miR-506 to suppress transcription. Overexpression of miR-506 inhibited TGFβ-induced EMT and suppressed adhesion, invasion, and migration of MDA-MB-231 cells. From these results, we concluded that miR-506 plays a key role in the process of EMT through posttranslational control of EMT-related genes.

  19. JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.

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    McMurtry, Vanity; Saavedra, Joseph E; Nieves-Alicea, René; Simeone, Ann-Marie; Keefer, Larry K; Tari, Ana M

    2011-04-01

    Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC50s of JS-K against the breast cancer cells ranged from 0.8 to 3 µM. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-µM concentration, and HMECs were unaffected by 10 µM JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective anti-tumor activity of JS-K warrants its further investigation in breast tumors.

  20. The 18-kDa translocator protein (TSPO) disrupts mammary epithelial morphogenesis and promotes breast cancer cell migration.

    Science.gov (United States)

    Wu, Xiaoting; Gallo, Kathleen A

    2013-01-01

    Mitochondria play important roles in cancer progression and have emerged as viable targets for cancer therapy. Increasing levels of the outer mitochondrial membrane protein, 18-kDa translocator protein (TSPO), are associated with advancing breast cancer stage. In particular, higher TSPO levels are found in estrogen receptor (ER)-negative breast tumors, compared with ER-positive tumors. In this study, we sought to define the roles of TSPO in the acquisition of breast cancer malignancy. Using a three-dimensional Matrigel culture system, we determined the impact of elevated TSPO levels on mammary epithelial morphogenesis. Our studies demonstrate that stable overexpression of TSPO in mammary epithelial MCF10A acini drives proliferation and provides partial resistance to luminal apoptosis, resulting in enlarged acinar structures with partially filled lumen that resemble early stage breast lesions leading to breast cancer. In breast cancer cell lines, TSPO silencing or TSPO overexpression significantly altered the migratory activity. In addition, we found that combination treatment with the TSPO ligands (PK 11195 or Ro5-4864) and lonidamine, a clinical phase II drug targeting mitochondria, decreased viability of ER-negative breast cancer cell lines. Taken together, these data demonstrate that increases in TSPO levels at different stages of breast cancer progression results in the acquisition of distinct properties associated with malignancy. Furthermore, targeting TSPO, particularly in combination with other mitochondria-targeting agents, may prove useful for the treatment of ER-negative breast cancer.

  1. The 18-kDa translocator protein (TSPO disrupts mammary epithelial morphogenesis and promotes breast cancer cell migration.

    Directory of Open Access Journals (Sweden)

    Xiaoting Wu

    Full Text Available Mitochondria play important roles in cancer progression and have emerged as viable targets for cancer therapy. Increasing levels of the outer mitochondrial membrane protein, 18-kDa translocator protein (TSPO, are associated with advancing breast cancer stage. In particular, higher TSPO levels are found in estrogen receptor (ER-negative breast tumors, compared with ER-positive tumors. In this study, we sought to define the roles of TSPO in the acquisition of breast cancer malignancy. Using a three-dimensional Matrigel culture system, we determined the impact of elevated TSPO levels on mammary epithelial morphogenesis. Our studies demonstrate that stable overexpression of TSPO in mammary epithelial MCF10A acini drives proliferation and provides partial resistance to luminal apoptosis, resulting in enlarged acinar structures with partially filled lumen that resemble early stage breast lesions leading to breast cancer. In breast cancer cell lines, TSPO silencing or TSPO overexpression significantly altered the migratory activity. In addition, we found that combination treatment with the TSPO ligands (PK 11195 or Ro5-4864 and lonidamine, a clinical phase II drug targeting mitochondria, decreased viability of ER-negative breast cancer cell lines. Taken together, these data demonstrate that increases in TSPO levels at different stages of breast cancer progression results in the acquisition of distinct properties associated with malignancy. Furthermore, targeting TSPO, particularly in combination with other mitochondria-targeting agents, may prove useful for the treatment of ER-negative breast cancer.

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

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    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.

  3. Endoplasmic reticulum protein 29 regulates epithelial cell integrity during the mesenchymal-epithelial transition in breast cancer cells.

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    Bambang, I F; Lee, Y K; Richardson, D R; Zhang, D

    2013-03-07

    The epithelial-mesenchymal transition (EMT) correlates with disruption of cell-cell adhesion, loss of cell polarity and development of epithelial cell malignancy. Identifying novel molecules that inhibit EMT has profound potential for developing mechanism-based therapeutics. We previously demonstrated that the endoplasmic reticulum protein 29 (ERp29) is a novel factor that can drive mesenchymal-epithelial transition (MET) and induce cell growth arrest in MDA-MB-231 cells. Here, we show that ERp29 is an important molecule in establishing epithelial cell integrity during the MET. We demonstrate that ERp29 regulates MET in a cell context-dependent manner. ERp29 overexpression induced a complete MET in mesenchymal MDA-MB-231 cells through downregulating the expression of transcriptional repressors (for example, Slug, Snai1, ZEB2 and Twist) of E-cadherin. In contrast, overexpression of ERp29 induces incomplete MET in basal-like BT549 cells in which the expression of EMT-related markers (for example, vimentin; cytokeratin 19 (CK19) and E-cadherin) and the transcriptional repressors of E-cadherin were not altered. However, ERp29 overexpression in both cell-types resulted in loss of filamentous stress fibers, formation of cortical actin and restoration of an epithelial phenotype. Mechanistic studies revealed that overexpression of ERp29 in both cell-types upregulated the expression of TJ proteins (zonula-occludens-1 (ZO-1) and occludin) and the core apical-basal polarity proteins (Par3 and Scribble) at the membrane to enhance cell-cell contact and cell polarization. Knockdown of ERp29 in the epithelial MCF-7 cells decreased the expression of these proteins, leading to the disruption of cell-cell adhesion. Taken together, ERp29 is a novel molecule that regulates MET and epithelial cell integrity in breast cancer cells.

  4. Benzyl isothiocyanate inhibits epithelial-mesenchymal transition in cultured and xenografted human breast cancer cells.

    Science.gov (United States)

    Sehrawat, Anuradha; Singh, Shivendra V

    2011-07-01

    We showed previously that cruciferous vegetable constituent benzyl isothiocyanate (BITC) inhibits growth of cultured and xenografted human breast cancer cells and suppresses mammary cancer development in a transgenic mouse model. We now show, for the first time, that BITC inhibits epithelial-mesenchymal transition (EMT) in human breast cancer cells. Exposure of estrogen-independent MDA-MB-231 and estrogen-responsive MCF-7 human breast cancer cell lines and a pancreatic cancer cell line (PL-45) to BITC resulted in upregulation of epithelial markers (e.g., E-cadherin and/or occludin) with a concomitant decrease in protein levels of mesenchymal markers, including vimentin, fibronectin, snail, and/or c-Met. The BITC-mediated induction of E-cadherin protein was accompanied by an increase in its transcription, whereas BITC-treated MDA-MB-231 cells exhibited suppression of vimentin, snail, and slug mRNA levels. Experimental EMT induced by exposure to TGFβ and TNFα or Rb knockdown in a spontaneously immortalized nontumorigenic human mammary epithelial cell line (MCF-10A) was also partially reversed by BITC treatment. The TGFβ-/TNFα-induced migration of MCF-10A cells was inhibited in the presence of BITC, which was partially attenuated by RNA interference of E-cadherin. Inhibition of MDA-MB-231 xenograft growth in vivo in female athymic mice by BITC administration was associated with an increase in protein level of E-cadherin and suppression of vimentin and fibronectin protein expression. In conclusion, this study reports a novel anticancer effect of BITC involving inhibition of EMT, a process triggered during progression of cancer to invasive state.

  5. Impact of tumour epithelial subtype on circulating microRNAs in breast cancer patients.

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    Peadar S Waters

    Full Text Available While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45. Three miRNAs of interest were then quantified in the circulation(n = 166 and tissue (n = 100 of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes >2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of

  6. Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1

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    Patrick P. Carriere

    2015-12-01

    Full Text Available Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT. Letrozole-resistant breast cancer cells (LTLT-Ca were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1 expression (4.51-fold, while glyceollin I treatment caused a −3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.

  7. Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients.

    Science.gov (United States)

    Raimondi, Cristina; Gradilone, Angela; Naso, Giuseppe; Vincenzi, Bruno; Petracca, Arianna; Nicolazzo, Chiara; Palazzo, Antonella; Saltarelli, Rosa; Spremberg, Franco; Cortesi, Enrico; Gazzaniga, Paola

    2011-11-01

    Currently used methods to detect and enumerate circulating tumor cells (CTCs) rely on the expression of the epithelial cell adhesion molecule (EpCAM) and cytokeratins. This selection may exclude cells that have undergone intrinsic modifications of their phenotype, as epithelial-mesenchymal transition (EMT). Aim of the study was to investigate the expression of EMT and stemness markers in CTCs from breast cancer patients in all stages of disease. 92 female breast cancer patients were enrolled. CTCs were isolated by CELLection Dynabeads coated with the monoclonal antibody toward EpCam. Samples found positive for CTCs presence (CD45-/CK+) were evaluated for the expression of ER alpha, HER2, ALDH1, vimentin, and fibronectin. Samples negative for CTCs presence (CD45-/CK-) were also evaluated for the expression of vimentin and fibronectin, used as markers of EMT. CTCs were found in 66% of patients. The distribution of CTCs presence according to stage and grade of disease was found statistically significant. The expression of ALDH1 on CTCs was found to correlate to stage of disease and to the expression of vimentin and fibronectin. In 34% of patients, we detected cells with negative CK/CD45 expression but positive expression of vimentin and fibronectin. There is an urgent need for optimizing CTCs detection methods through the inclusion of EMT markers. The detection of cells in mesenchymal transition, retaining EMT and stemness features, may contribute to discover additional therapeutic targets useful to eradicate micrometastatic disease in breast cancer.

  8. Extracellular vesicles from women with breast cancer promote an epithelial-mesenchymal transition-like process in mammary epithelial cells MCF10A.

    Science.gov (United States)

    Galindo-Hernandez, Octavio; Gonzales-Vazquez, Cristina; Cortes-Reynosa, Pedro; Reyes-Uribe, Emmanuel; Chavez-Ocaña, Sonia; Reyes-Hernandez, Octavio; Sierra-Martinez, Mónica; Salazar, Eduardo Perez

    2015-12-01

    Extracellular vesicles (EVs) mediate many stages of tumor progression including angiogenesis, escape from immune surveillance, and extracellular matrix degradation. We studied whether EVs from plasma of women with breast cancer are able to induce an epithelial-mesenchymal transition (EMT) process in mammary epithelial cells MCF10A. Our findings demonstrate that EVs from plasma of breast cancer patients induce a downregulation of E-cadherin expression and an increase of vimentin and N-cadherin expression. Moreover, EVs induce migration and invasion, as well as an increase of NFκB-DNA binding activity and MMP-2 and MMP-9 secretions. In summary, our findings demonstrate, for the first time, that EVs from breast cancer patients induce an EMT-like process in human mammary non-tumorigenic epithelial cells MCF10A.

  9. The Roles of Epithelial-to-Mesenchymal Transition (EMT and Mesenchymal-to-Epithelial Transition (MET in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment

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    Binnaz Demirkan

    2013-11-01

    Full Text Available Many studies have revealed molecular connections between breast and bone. Genes, important in the control of bone remodeling, such as receptor activator of nuclear kappa (RANK, receptor activator of nuclear kappa ligand (RANKL, vitamin D, bone sialoprotein (BSP, osteopontin (OPN, and calcitonin, are expressed in breast cancer and lactating breast. Epithelial-mesenchymal transition (EMT and mesenchymal-epithelial transition (MET effectors play critical roles during embryonic development, postnatal growth, and epithelial homeostasis, but also are involved in a number of pathological conditions, including wound repair, fibrosis, inflammation, as well as cancer progression and bone metastasis. Transforming growth factor β (TGFβ, insulin-like growth factor I & II (IGF I & II, platelet-derived growth factor (PDGF, parathyroid hormone-related protein (PTH(rP, vascular endothelial growth factor (VEGF, epithelial growth factors II/I (ErbB/EGF, interleukin 6 (IL-6, IL-8, IL-11, IL-1, integrin αvβ3, matrix metalloproteinases (MMPs, catepsin K, hypoxia, notch, Wnt, bone morphogenetic proteins (BMP, and hedgehog signaling pathways are important EMT and MET effectors identified in the bone microenviroment facilitating bone metastasis formation. Recently, Runx2, an essential transcription factor in the regulation of mesenchymal cell differentiation into the osteoblast lineage and proper bone development, is also well-recognized for its expression in breast cancer cells promoting osteolytic bone metastasis. Understanding the precise mechanisms of EMT and MET in the pathogenesis of breast cancer bone metastasis can inform the direction of therapeutic intervention and possibly prevention.

  10. Inositol induces mesenchymal-epithelial reversion in breast cancer cells through cytoskeleton rearrangement.

    Science.gov (United States)

    Dinicola, Simona; Fabrizi, Gianmarco; Masiello, Maria Grazia; Proietti, Sara; Palombo, Alessandro; Minini, Mirko; Harrath, Abdel Halim; Alwasel, Saleh H; Ricci, Giulia; Catizone, Angela; Cucina, Alessandra; Bizzarri, Mariano

    2016-07-01

    Inositol displays multi-targeted effects on many biochemical pathways involved in epithelial-mesenchymal transition (EMT). As Akt activation is inhibited by inositol, we investigated if such effect could hamper EMT in MDA-MB-231 breast cancer cells. In cancer cells treated with pharmacological doses of inositol E-cadherin was increased, β-catenin was redistributed behind cell membrane, and metalloproteinase-9 was significantly reduced, while motility and invading capacity were severely inhibited. Those changes were associated with a significant down-regulation of PI3K/Akt activity, leading to a decrease in downstream signaling effectors: NF-kB, COX-2, and SNAI1. Inositol-mediated inhibition of PS1 leads to lowered Notch 1 release, thus contributing in decreasing SNAI1 levels. Overall, these data indicated that inositol inhibits the principal molecular pathway supporting EMT. Similar results were obtained in ZR-75, a highly metastatic breast cancer line. These findings are coupled with significant changes on cytoskeleton. Inositol slowed-down vimentin expression in cells placed behind the wound-healing edge and stabilized cortical F-actin. Moreover, lamellipodia and filopodia, two specific membrane extensions enabling cell migration and invasiveness, were no longer detectable after inositol addiction. Additionally, fascin and cofilin, two mandatory required components for F-actin assembling within cell protrusions, were highly reduced. These data suggest that inositol may induce an EMT reversion in breast cancer cells, suppressing motility and invasiveness through cytoskeleton modifications.

  11. Contribution of xanthine oxidoreductase to mammary epithelial and breast cancer cell differentiation in part modulates inhibitor of differentiation-1.

    Science.gov (United States)

    Fini, Mehdi A; Monks, Jenifer; Farabaugh, Susan M; Wright, Richard M

    2011-09-01

    Loss of xanthine oxidoreductase (XOR) has been linked to aggressive breast cancer in vivo and to breast cancer cell aggressiveness in vitro. In the present study, we hypothesized that the contribution of XOR to the development of the normal mammary gland may underlie its capacity to modulate breast cancer. We contrasted in vitro and in vivo developmental systems by differentiation marker and microarray analyses. Human breast cancer microarray was used for clinical outcome studies. The role of XOR in differentiation and proliferation was examined in human breast cancer cells and in a mouse xenograft model. Our data show that XOR was required for functional differentiation of mammary epithelial cells both in vitro and in vivo. Poor XOR expression was observed in a mouse ErbB2 breast cancer model, and pharmacologic inhibition of XOR increased breast cancer tumor burden in mouse xenograft. mRNA microarray analysis of human breast cancer revealed that low XOR expression was significantly associated with time to tumor relapse. The opposing expression of XOR and inhibitor of differentiation-1 (Id1) during HC11 differentiation and mammary gland development suggested a potential functional relationship. While overexpression of Id1 inhibited HC11 differentiation and XOR expression, XOR itself modulated expression of Id1 in differentiating HC11 cells. Overexpression of XOR both inhibited Id1-induced proliferation and -stimulated differentiation of Heregulin-β1-treated human breast cancer cells. These results show that XOR is an important functional component of differentiation whose diminished expression contributes to breast cancer aggressiveness, and they support XOR as both a breast cancer biomarker and a target for pharmacologic activation in therapeutic management of aggressive breast cancer.

  12. Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent.

    Science.gov (United States)

    Davis, F M; Azimi, I; Faville, R A; Peters, A A; Jalink, K; Putney, J W; Goodhill, G J; Thompson, E W; Roberts-Thomson, S J; Monteith, G R

    2014-05-01

    Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of

  13. Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

    Science.gov (United States)

    Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J; Shin, Seungjin; Jeruss, Jacqueline S; Shea, Lonnie D

    2013-01-01

    The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

  14. Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

    Directory of Open Access Journals (Sweden)

    Anaar Siletz

    Full Text Available The epithelial-mesenchymal transition (EMT is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

  15. Clinical implications of circulating tumor cells of breast cancer patients: role of epithelial mesenchymal plasticity

    Directory of Open Access Journals (Sweden)

    Linda Maria McInnes

    2015-02-01

    Full Text Available There is increasing interest in circulating tumor cells (CTCs due to their purported role in breast cancer metastasis, and their potential as a ‘liquid biopsy’ tool in breast cancer diagnosis and management. There are, however, questions with regards to the reliability and consistency of CTC detection and to the relationship between CTCs and prognosis, which is limiting their clinical utility. There is increasing acceptance that the ability of CTCs to alter from an epithelial to mesenchymal phenotype plays an important role in determining the metastatic potential of these cells. This review examines the phenotypic and genetic variation, which has been reported within CTC populations. Importantly, we discuss how the detection and characterization of CTCs provides additional and often differing information from that obtained from the primary tumor, and how this may be utilized in determining prognosis and treatment options. It has been shown for example that hormone receptor status often differs between the primary tumor and CTCs, which may help to explain failure of endocrine treatment. We examine how CTC status may introduce alternative treatment options and also how they may be used to monitor treatment. Finally, we discuss the most interesting current clinical trials involving CTC analysis and note further research that is required before the breast cancer liquid biopsy can be realised.

  16. Mammary epithelial morphogenesis and early breast cancer. Evidence of involvement of basal components of the RNA Polymerase I transcription machinery.

    Science.gov (United States)

    Rossetti, Stefano; Wierzbicki, Andrzej J; Sacchi, Nicoletta

    2016-09-16

    Upregulation of RNA Polymerase (Pol I)-mediated transcription of rRNA and increased ribogenesis are hallmarks of breast cancer. According to several datasets, including The Cancer Genome Atlas (TCGA), amplification/upregulation of genes encoding for basal components of the Pol I transcriptional machinery is frequent at different breast cancer stages. Here we show that knock down of the RNA polymerase I-specific transcription initiation factor RRN3 (TIF-IA) in breast cancer cells is sufficient to reduce rRNA synthesis and inhibit cell proliferation, and second that stable ectopic expression of RRN3 in human mammary epithelial (HME1) cells, by increasing rRNA transcription, confers increased sensitivity to the anti-proliferative effects of a selective Pol I inhibitor. Further, RRN3-overexpressing HME1 cells, when grown in in vitro 3-dimensional (3D) culture, develop into morphologically aberrant acinar structures lacking a lumen and filled with proliferative cells, thus acquiring a morphology resembling in situ ductal breast cancer lesions (DCIS). Consequently, interference with RRN3 control of Pol I transcription seems capable of both compromising mammary epithelial morphogenetic processes at early breast cancer stages, and driving breast cancer progression by fostering proliferation.

  17. Selective androgen receptor modulators (SARMs negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

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    Ramesh Narayanan

    Full Text Available The androgen receptor (AR is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer.Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC co-culture signaling studies were performed to understand the mechanisms of action.Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures.1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

  18. Differential subcellular localization renders HAI-2 a matriptase inhibitor in breast cancer cells but not in mammary epithelial cells.

    Science.gov (United States)

    Chang, Hsiang-Hua D; Xu, Yuan; Lai, Hongyu; Yang, Xiaoyu; Tseng, Chun-Che; Lai, Ying-Jung J; Pan, Yu; Zhou, Emily; Johnson, Michael D; Wang, Jehng-Kang; Lin, Chen-Yong

    2015-01-01

    The type 2 transmembrane serine protease matriptase is under tight control primarily by the actions of the integral membrane Kunitz-type serine protease inhibitor HAI-1. Growing evidence indicates that HAI-2 might also be involved in matriptase inhibition in some contexts. Here we showed that matriptase inhibition by HAI-2 depends on the subcellular localizations of HAI-2, and is observed in breast cancer cells but not in mammary epithelial cells. HAI-2 is co-expressed with matriptase in 21 out of 26 human epithelial and carcinoma cells examined. HAI-2 is also a potent matriptase inhibitor in solution, but in spite of this, HAI-2 inhibition of matriptase is not observed in all contexts where HAI-2 is expressed, unlike what is seen for HAI-1. Induction of matriptase zymogen activation in mammary epithelial cells results in the formation of matriptase-HAI-1 complexes, but matriptase-HAI-2 complexes are not observed. In breast cancer cells, however, in addition to the appearance of matriptase-HAI-1 complex, three different matriptase-HAI-2 complexes, are formed following the induction of matriptase activation. Immunofluorescent staining reveals that activated matriptase is focused at the cell-cell junctions upon the induction of matriptase zymogen activation in both mammary epithelial cells and breast cancer cells. HAI-2, in contrast, remains localized in vesicle/granule-like structures during matriptase zymogen activation in human mammary epithelial cells. In breast cancer cells, however, a proportion of the HAI-2 reaches the cell surface where it can gain access to and inhibit active matriptase. Collectively, these data suggest that matriptase inhibition by HAI-2 requires the translocation of HAI-2 to the cell surface, a process which is observed in some breast cancer cells but not in mammary epithelial cells.

  19. Activation of apoptosis in NAF-1-deficient human epithelial breast cancer cells

    Science.gov (United States)

    Holt, Sarah H.; Darash-Yahana, Merav; Sohn, Yang Sung; Song, Luhua; Karmi, Ola; Tamir, Sagi; Michaeli, Dorit; Luo, Yuting; Paddock, Mark L.; Jennings, Patricia A.; Onuchic, José N.; Azad, Rajeev K.; Pikarsky, Eli; Cabantchik, Ioav Z.; Nechushtai, Rachel; Mittler, Ron

    2016-01-01

    ABSTRACT Maintaining iron (Fe) ion and reactive oxygen species homeostasis is essential for cellular function, mitochondrial integrity and the regulation of cell death pathways, and is recognized as a key process underlying the molecular basis of aging and various diseases, such as diabetes, neurodegenerative diseases and cancer. Nutrient-deprivation autophagy factor 1 (NAF-1; also known as CISD2) belongs to a newly discovered class of Fe-sulfur proteins that are localized to the outer mitochondrial membrane and the endoplasmic reticulum. It has been implicated in regulating homeostasis of Fe ions, as well as the activation of autophagy through interaction with BCL-2. Here we show that small hairpin (sh)RNA-mediated suppression of NAF-1 results in the activation of apoptosis in epithelial breast cancer cells and xenograft tumors. Suppression of NAF-1 resulted in increased uptake of Fe ions into cells, a metabolic shift that rendered cells more susceptible to a glycolysis inhibitor, and the activation of cellular stress pathways that are associated with HIF1α. Our studies suggest that NAF-1 is a major player in the metabolic regulation of breast cancer cells through its effects on cellular Fe ion distribution, mitochondrial metabolism and the induction of apoptosis. PMID:26621032

  20. TP53 Mutation, Epithelial-Mesenchymal Transition, and Stemlike Features in Breast Cancer Subtypes

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    Danila Coradini

    2012-01-01

    Full Text Available Altered p53 protein is prevalently associated with the pathologic class of triple-negative breast cancers and loss of p53 function has recently been linked to the induction of an epithelial-mesenchymal transition (EMT and acquisition of stemness properties. We explored the association between TP53 mutational status and expression of some genes involved in the canonical TGF-β signaling pathway (the most potent EMT inducer and in two early EMT associated events: loss of cell polarity and acquisition of stemness-associated features. We used a publicly accessible microarray dataset consisting of 251 p53-sequenced primary breast cancers. Statistical analysis indicated that mutant p53 tumors (especially those harboring a severe mutation were consistent with the aggressive class of triple-negative cancers and that, differently from cell cultures, surgical tumors underexpressed some TGF-β related transcription factors known as involved in EMT (ID1, ID4, SMAD3, SMAD4, SMAD5, ZEB1. These unexpected findings suggest an interesting relationship between p53 mutation, mammary cell dedifferentiation, and the concomitant acquisition of stemlike properties (as indicated by the overexpression of PROM1 and NOTCH1 genes, which improve tumor cells aggressiveness as indicated by the overexpression of genes associated with cell proliferation (CDK4, CDK6, MKI67 and migration (CXCR4, MMP1.

  1. Salinomycin suppresses TGF-β1-induced epithelial-to-mesenchymal transition in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Zhang, Chunying; Lu, Ying; Li, Qing; Mao, Jun; Hou, Zhenhuan; Yu, Xiaotang; Fan, Shujun; Li, Jiazhi; Gao, Tong; Yan, Bing; Wang, Bo; Song, Bo; Li, Lianhong

    2016-03-25

    Epithelial-to-mesenchymal transition (EMT) is the major cause of breast cancer to initiate invasion and metastasis. Salinomycin (Sal) has been found as an effective chemical compound to kill breast cancer stem cells. However, the effect of Sal on invasion and metastasis of breast cancer is unclear. In the present study, we showed that Sal reversed transforming growth factor-β1 (TGF-β1) induced invasion and metastasis accompanied with down-regulation of MMP-2 by experiments on human breast cancer cell line MCF-7. Sal was able to inhibit TGF-β1-induced EMT phenotypic transition and the activation of key signaling molecules involved in Smad (p-Smad2/3,Snail1) and non-Smad (β-catenin, p-p38 MAPK) signals which cooperatively regulate the induction of EMT. Importantly, in a series of breast cancer specimens, we found strong correlation among E-cadherin expression, β-catenin expression, and the lymph node metastatic potential of breast cancer. Our research suggests that Sal is promised to be a chemotherapeutic drug by suppressing the metastasis of breast cancer.

  2. Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells.

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    Evan N Cohen

    Full Text Available Inflammatory breast cancer (IBC is the most insidious form of locally advanced breast cancer; about a third of patients have distant metastasis at initial staging. Emerging evidence suggests that host factors in the tumor microenvironment may interact with underlying IBC cells to make them aggressive. It is unknown whether immune cells associated to the IBC microenvironment play a role in this scenario to transiently promote epithelial to mesenchymal transition (EMT in these cells. We hypothesized that soluble factors secreted by activated immune cells can induce an EMT in IBC and thus promote metastasis. In a pilot study of 16 breast cancer patients, TNF-α production by peripheral blood T cells was correlated with the detection of circulating tumor cells expressing EMT markers. In a variety of IBC model cell lines, soluble factors from activated T cells induced expression of EMT-related genes, including FN1, VIM, TGM2, ZEB1. Interestingly, although IBC cells exhibited increased invasion and migration following exposure to immune factors, the expression of E-cadherin (CDH1, a cell adhesion molecule, increased uniquely in IBC cell lines but not in non-IBC cell lines. A combination of TNF-α, IL-6, and TGF-β was able to recapitulate EMT induction in IBC, and conditioned media preloaded with neutralizing antibodies against these factors exhibited decreased EMT. These data suggest that release of cytokines by activated immune cells may contribute to the aggressiveness of IBC and highlight these factors as potential target mediators of immune-IBC interaction.

  3. Snail promotes epithelial mesenchymal transition in breast cancer cells in part via activation of nuclear ERK2.

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    Bethany N Smith

    Full Text Available Snail transcription factor is up-regulated in several cancers and associated with increased tumor migration and invasion via induction of epithelial-to-mesenchymal transition (EMT. MAPK (ERK1/2 signaling regulates cellular processes including cell motility, adhesion, and invasion. We investigated the regulation of ERK1/2 by Snail in breast cancer cells. ERK1/2 activity (p-ERK was higher in breast cancer patient tissue as compared to normal tissue. Snail and p-ERK were increased in several breast cancer cell lines as compared to normal mammary epithelial cells. Snail knockdown in MDA-MB-231 and T47-D breast cancer cells decreased or re-localized p-ERK from the nuclear compartment to the cytoplasm. Snail overexpression in MCF-7 breast cancer cells induced EMT, increased cell migration, decreased cell adhesion and also increased tumorigenicity. Snail induced nuclear translocation of p-ERK, and the activation of its subcellular downstream effector, Elk-1. Inhibiting MAPK activity with UO126 or knockdown of ERK2 isoform with siRNA in MCF-7 Snail cells reverted EMT induced by Snail as shown by decreased Snail and vimentin expression, decreased cell migration and increased cell adhesion. Overall, our data suggest that ERK2 isoform activation by Snail in aggressive breast cancer cells leads to EMT associated with increased cell migration and decreased cell adhesion. This regulation is enhanced by positive feedback regulation of Snail by ERK2. Therefore, therapeutic targeting of ERK2 isoform may be beneficial for breast cancer.

  4. 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.

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

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    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.

  6. The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women.

    Science.gov (United States)

    Huh, Sung Jin; Oh, Hannah; Peterson, Michael A; Almendro, Vanessa; Hu, Rong; Bowden, Michaela; Lis, Rosina L; Cotter, Maura B; Loda, Massimo; Barry, William T; Polyak, Kornelia; Tamimi, Rulla M

    2016-04-01

    The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case-control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67(+) cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12-48.0]. Conversely, the frequency of ER(+) or p27(+) cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER(+): OR = 0.70, 95% CI, 0.33-1.50; p27(+): OR = 0.89, 95% CI, 0.45-1.75). Notably, high Ki67(+)/low p27(+) and high Ki67(+)/low ER(+) cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67(+)/low p27(+) and low Ki67(+)/low ER(+) cell frequencies, respectively, among premenopausal women (Ki67(hi)/p27(lo): OR = 5.08, 95% CI, 1.43-18.1; Ki67(hi)/ER(lo): OR = 4.68, 95% CI, 1.63-13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. Cancer Res; 76(7); 1926-34. ©2016 AACR.

  7. Tracing anti-cancer and cancer-promoting actions of all-trans retinoic acid in breast cancer to a RARα epigenetic mechanism of mammary epithelial cell fate.

    Science.gov (United States)

    Rossetti, Stefano; Ren, MingQiang; Visconti, Nicolo; Corlazzoli, Francesca; Gagliostro, Vincenzo; Somenzi, Giulia; Yao, Jin; Sun, Yijun; Sacchi, Nicoletta

    2016-12-27

    A hallmark of cancer cells is the ability to evade the growth inhibitory/pro-apoptotic action of physiological all-trans retinoic acid (RA) signal, the bioactive derivative of Vitamin A. However, as we and others reported, RA can also promote cancer cell growth and invasion. Here we show that anticancer and cancer-promoting RA actions in breast cancer have roots in a mechanism of mammary epithelial cell morphogenesis that involves both transcriptional (epigenetic) and non-transcriptional RARα (RARA) functions. We found that the mammary epithelial cell-context specific degree of functionality of the RARA transcriptional (epigenetic) component of this mechanism, by tuning the effects of the non-transcriptional RARA component, determines different cell fate decisions during mammary morphogenesis. Indeed, factors that hamper the RARA epigenetic function make physiological RA drive aberrant morphogenesis via non-transcriptional RARA, thus leading to cell transformation. Remarkably, also the cell context-specific degree of functionality of the RARA epigenetic component retained by breast cancer cells is critical to determine cell fate decisions in response to physiological as well as supraphysiological RA variation. Overall this study supports the proof of principle that the epigenetic functional plasticity of the mammary epithelial cell RARA mechanism, which is essential for normal morphogenetic processes, is necessary to deter breast cancer onset/progression consequent to the insidious action of physiological RA.

  8. Elucidation of epithelial-mesenchymal transition-related pathways in a triple-negative breast cancer cell line model by multi-omics interactome analysis

    DEFF Research Database (Denmark)

    Pauling, Josch K; Christensen, Anne G; Batra, Richa

    2014-01-01

    obtained from a triple-negative breast cancer cell line model, combining data sets of gene and protein expression as well as protein phosphorylation. We focus on alterations associated with the phenotypical differences arising from epithelial-mesenchymal transition in two breast cancer cell lines...

  9. Inhibition of RAB1A suppresses epithelial-mesenchymal transition and proliferation of triple-negative breast cancer cells.

    Science.gov (United States)

    Xu, Hui; Qian, Mingping; Zhao, Bingkun; Wu, Chenyang; Maskey, Niraj; Song, Hongming; Li, Dengfeng; Song, Jialu; Hua, Kaiyao; Fang, Lin

    2017-03-01

    RAB1A acts as an oncogene in various cancers, and emerging evidence has verified that RAB1A is an mTORC1 activator in hepatocellular and colorectal cancer, but the role of RAB1A in breast cancer remains unclear. In this investigation, RAB1A siRNA was successfully transfected in MDA-MB-231 and BT-549 human triple-negative breast cancer cells, and verified by real‑time quantitative polymerase chain reaction and western blotting. Then, MTT cell proliferation, colony formation, cell invasion and wound healing assays were performed to characterize the function of RAB1A in the breast cancer cell lines. Downregulation of RAB1A inhibited cellular growth, cell migration, cell invasion and cell epithelial-mesenchymal transition. Furthermore, compared with NC siRNA transfected cells, RAB1A siRNA transfected breast cancer cells inhibited the phosphorylation of S6K1, the effector molecular of mTORC1. Collectively, our data suggested that RAB1A acts as an oncogene by regulating cellular proliferation, growth, invasion and metastasis via activation of mTORC1 pathway in triple-negative breast cancer.

  10. 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 ...

  11. Functional Characteristics of Tumor-Associated Protein Spot14 and Interacting Proteins in Mouse Mammary Epithelial and Breast Cancer Cell Lines

    Science.gov (United States)

    2009-09-01

    Interacting Proteins in Mouse Mammary Epithelial and Breast Cancer Cell Lines PRINCIPAL INVESTIGATOR: Michael C. Rudolph, B.A...Spot14 and Interacting Proteins in Mouse Mammary Epithelial and 5b. GRANT NUMBER W81XWH-08-1-0596 Breast Cancer Cell Lines 5c. PROGRAM ELEMENT...S14 and to identify potential S14 interacting proteins that confer its function. Body The overarching goals of this proposal are to examine the

  12. Hybrid cells derived from breast epithelial cell/breast cancer cell fusion events show a differential RAF-AKT crosstalk

    Directory of Open Access Journals (Sweden)

    Özel Cem

    2012-04-01

    Full Text Available Abstract Background The biological phenomenon of cell fusion has been linked to several characteristics of tumour progression, including an enhanced metastatogenic capacity and an enhanced drug resistance of hybrid cells. We demonstrated recently that M13SV1-EGFP-Neo breast epithelial cells exhibiting stem cell characteristics spontaneously fused with MDA-MB-435-Hyg breast cancer cells, thereby giving rise to stable M13MDA435 hybrid cells, which are characterised by a unique gene expression profile and migratory behaviour. Here we investigated the involvement of the PLC-β/γ1, PI3K/AKT and RAS-RAF-ERK signal transduction cascades in the EGF and SDF-1α induced migration of two M13MDA435 hybrid cell clones in comparison to their parental cells. Results Analysis of the migratory behaviour by using the three-dimensional collagen matrix migration assay showed that M13SV1-EGFP-Neo cells as well as M13MDA435 hybrid cells, but not the breast cancer cell line, responded to EGF stimulation with an increased locomotory activity. By contrast, SDF-1α solely stimulated the migration of M13SV1-EGFP-Neo cells, whereas the migratory activity of the other cell lines was blocked. Analysis of signal transduction cascades revealed a putative differential RAF-AKT crosstalk in M13MDA435-1 and -3 hybrid cell clones. The PI3K inhibitor Ly294002 effectively blocked the EGF induced migration of M13MDA435-3 hybrid cells, whereas the EGF induced locomotion of M13MDA435-1 hybrid cells was markedly increased. Analysis of RAF-1 S259 phosphorylation, being a major mediator of the negative regulation of RAF-1 by AKT, showed decreased pRAF-1 S259 levels in LY294002 treated M13MDA435-1 hybrid cells. By contrast, pRAF-1 S259 levels remained unaltered in the other cell lines. Inhibition of PI3K/AKT signalling by Ly294002 relieves the AKT mediated phosphorylation of RAF-1, thereby restoring MAPK signalling. Conclusions Here we show that hybrid cells could evolve exhibiting a

  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. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers.

    Directory of Open Access Journals (Sweden)

    Jonathan Beesley

    Full Text Available Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC. We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.

  15. Anti-Cancer Activity of Solanum nigrum (AESN through Suppression of Mitochondrial Function and Epithelial-Mesenchymal Transition (EMT in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ying-Jang Lai

    2016-04-01

    Full Text Available Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.

  16. Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway.

    Science.gov (United States)

    Qin, Ge; Xu, Fei; Qin, Tao; Zheng, Qiufan; Shi, Dingbo; Xia, Wen; Tian, Yun; Tang, Yanlai; Wang, Jingshu; Xiao, Xiangshen; Deng, Wuguo; Wang, Shusen

    2015-12-08

    Palbociclib, a highly selective CDK4/6 inhibitor, has been shown to be a novel anti-tumor agent that suppresses breast cancer cell proliferation. However, its anti-metastasis activity remains controversial. In the present study, we evaluated whether palbociclib prevented breast cancer cell metastasis and revealed its regulatory mechanism. We found that palbociclib inhibited migration and invasion in the breast cancer cells MDA-MB-231 and T47D. The epithelial-mesenchymal transition (EMT) markers, vimentin and Snail, were down-regulated with palbociclib treatment. Moreover, we revealed that this inhibition was mediated by the c-Jun/COX-2 pathway. COX-2 was decreased after palbociclib treatment. The production of PGE2 was also reduced along with COX-2. Additionally, our data showed that c-Jun, a crucial transcriptional regulator of COX-2, was down-regulated by palbociclib. We found that palbociclib weakened the COX-2 promoter binding activity of c-Jun and prevented its translocation from the cytoplasm to cell nuclei. Bioluminescence imaging and tail intravenous injection were used to evaluate the anti-metastasis effect of palbociclib in vivo. The data demonstrated that palbociclib reduced breast cancer metastasis to the lung. These results therefore demonstrated that the anti-metastasis activity of palbociclib is mediated via the c-Jun/COX-2 signaling pathway by inhibiting EMT in breast cancer cells.

  17. 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.

  18. Identifying breast cancer risk loci by global differential allele-specific expression (DASE analysis in mammary epithelial transcriptome

    Directory of Open Access Journals (Sweden)

    Gao Chuan

    2012-10-01

    Full Text Available Abstract Background The significant mortality associated with breast cancer (BCa suggests a need to improve current research strategies to identify new genes that predispose women to breast cancer. Differential allele-specific expression (DASE has been shown to contribute to phenotypic variables in humans and recently to the pathogenesis of cancer. We previously reported that nonsense-mediated mRNA decay (NMD could lead to DASE of BRCA1/2, which is associated with elevated susceptibility to breast cancer. In addition to truncation mutations, multiple genetic and epigenetic factors can contribute to DASE, and we propose that DASE is a functional index for cis-acting regulatory variants and pathogenic mutations, and that global analysis of DASE in breast cancer precursor tissues can be used to identify novel causative alleles for breast cancer susceptibility. Results To test our hypothesis, we employed the Illumina® Omni1-Quad BeadChip in paired genomic DNA (gDNA and double-stranded cDNA (ds-cDNA samples prepared from eight BCa patient-derived normal mammary epithelial lines (HMEC. We filtered original array data according to heterozygous genotype calls and calculated DASE values using the Log ratio of cDNA allele intensity, which was normalized to the corresponding gDNA. We developed two statistical methods, SNP- and gene-based approaches, which allowed us to identify a list of 60 candidate DASE loci (DASE ≥ 2.00, P ≤ 0.01, FDR ≤ 0.05 by both methods. Ingenuity Pathway Analysis of DASE loci revealed one major breast cancer-relevant interaction network, which includes two known cancer causative genes, ZNF331 (DASE = 2.31, P = 0.0018, FDR = 0.040 and USP6 (DASE = 4.80, P = 0.0013, FDR = 0.013, and a breast cancer causative gene, DMBT1 (DASE=2.03, P = 0.0017, FDR = 0.014. Sequence analysis of a 5′ RACE product of DMBT1 demonstrated that rs2981745, a putative breast cancer risk locus, appears to be one of the causal variants leading to DASE

  19. 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 ...

  20. The role of the breast cancer susceptibility gene 1 (BRCA1 in sporadic epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Mueller Christopher R

    2003-10-01

    Full Text Available Abstract Mutations within the BRCA1 tumor suppressor gene occur frequently in familial epithelial ovarian carcinomas but they are a rare event in the much more prevalent sporadic form of the disease. However, decreased BRCA1 expression occurs frequently in sporadic tumors, and the magnitude of this decrease has been correlated with increased disease progression. The near absence of somatic mutations consequently suggests that there are alternative mechanisms that may contribute to the observed loss of BRCA1 in sporadic tumors. Indeed, both allelic loss at the BRCA1 locus and epigenetic hypermethylation of the BRCA1 promoter play an important role in BRCA1 down-regulation; yet these mechanisms alone or in combination do not always account for the reduced BRCA1 expression. Alternatively, misregulation of specific upstream factors that control BRCA1 transcription may be a crucial means by which BRCA1 is lost. Therefore, determining how regulators of BRCA1 expression may be co-opted during sporadic ovarian tumorigenesis will lead to a better understanding of ovarian cancer etiology and it may help foster the future development of novel therapeutic strategies aimed at halting ovarian tumor progression.

  1. Parabens can enable hallmarks and characteristics of cancer in human breast epithelial cells: a review of the literature with reference to new exposure data and regulatory status.

    Science.gov (United States)

    Darbre, Philippa D; Harvey, Philip W

    2014-09-01

    A framework for understanding the complexity of cancer development was established by Hanahan and Weinberg in their definition of the hallmarks of cancer. In this review, we consider the evidence that parabens can enable development in human breast epithelial cells of four of six of the basic hallmarks, one of two of the emerging hallmarks and one of two of the enabling characteristics. In Hallmark 1, parabens have been measured as present in 99% of human breast tissue samples, possess oestrogenic activity and can stimulate sustained proliferation of human breast cancer cells at concentrations measurable in the breast. In Hallmark 2, parabens can inhibit the suppression of breast cancer cell growth by hydroxytamoxifen, and through binding to the oestrogen-related receptor gamma may prevent its deactivation by growth inhibitors. In Hallmark 3, in the 10 nm-1 μm range, parabens give a dose-dependent evasion of apoptosis in high-risk donor breast epithelial cells. In Hallmark 4, long-term exposure (>20 weeks) to parabens leads to increased migratory and invasive activity in human breast cancer cells, properties that are linked to the metastatic process. As an emerging hallmark methylparaben has been shown in human breast epithelial cells to increase mTOR, a key regulator of energy metabolism. As an enabling characteristic parabens can cause DNA damage at high concentrations in the short term but more work is needed to investigate long-term, low-dose mixtures. The ability of parabens to enable multiple cancer hallmarks in human breast epithelial cells provides grounds for regulatory review of the implications of the presence of parabens in human breast tissue.

  2. 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. ...

  3. SHOX2 Is a Direct miR-375 Target and a Novel Epithelial-to-Mesenchymal Transition Inducer in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sungguan Hong

    2014-04-01

    Full Text Available MicroRNAs have added a new dimension to our understanding of tumorigenesis and associated processes like epithelial-to-mesenchymal transition (EMT. Here, we show that miR-375 is elevated in epithelial-like breast cancer cells, and ectopic miR-375 expression suppresses EMT in mesenchymal-like breast cancer cells. We identified short stature homeobox 2 (SHOX2 as a miR-375 target, and miR-375–mediated suppression in EMT was reversed by forced SHOX2 expression. Ectopic SHOX2 expression can induce EMT in epithelial-like breast cancer cells, whereas SHOX2 knockdown diminishes EMT traits in mesenchymal-like breast cancer cells, demonstrating SHOX2 as an EMT inducer. We show that SHOX2 acts as a transcription factor to upregulate transforming growth factor β receptor I (TβR-I expression, and TβR-I inhibitor LY364947 abolishes EMT elicited by ectopic SHOX2 expression, suggesting that transforming growth factor β signaling is essential for SHOX2-induced EMT. Manipulating SHOX2 abundance in breast cancer cells impact in vitro invasion and in vivo dissemination. Analysis of breast tumor microarray database revealed that high SHOX2 expression significantly correlates with poor patient survival. Our study supports a critical role of SHOX2 in breast tumorigenicity.

  4. Downregulation of β-catenin decreases the tumorigenicity, but promotes epithelial-mesenchymal transition in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Kai Cai

    2014-01-01

    Full Text Available Background: Wnt/β-catenin signaling pathway plays a key role in human breast cancer progression. In this study, we down regulated β-catenin expression in human breast cancer MDA-MB-231 cells and investigated the effect of β-catenin knockdown on the cell biological characteristics. Materials and Methods: The recombinant plasmids of pSUPER-enhancement green fluorescent protein 1 (EGFP1-scrabble-β-catenin-short hairpin ribonucleic acid (shRNA and pSUPER-EGFP1-β-catenin-shRNA-1 were transfected into MDA-MB-231 cells, respectively, and the stably transfected cells were isolated from G418 selected clones. The β-catenin gene silenced efficiency was measured by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR and Western blot. The biological characteristics of MDA-MB-231 cells with down regulated β-catenin were evaluated by analyzing cell proliferation, clonogenicity, cell mobility and tumorigenicity. The expression of E-cadherin and Vimentin was concurrently detected by QRT-PCR. Results: The β-catenin-shRNA-1 stably transfected MDA-MB-231 cells significantly decreased β-catenin expression, cell proliferation, clonogenicity, and tumorigenicity in Balb/c nude mice compared with the MDA-MB-231 cells transfected with pSUPER-EGFP1-scrabble-β-catenin-shRNA. Interestingly, knockdown of β-catenin led to the reduction of epithelial E-cadherin expression, the increase of cell mobility and mesenchymal vimentin expression in MDA-MB-231 cells, indicating an epithelial to mesenchymal transition. Conclusion: Knockdown of β-catenin expression in human breast cancer MDA-MB-231 cells inhibits cell tumorigenicity in mice, but promotes cell epithelial-mesenchymal transition.

  5. Inhibition of Breast Cancer Progression by Blocking Heterocellular Contact Between Epithelial Cells and Fibroblasts

    Science.gov (United States)

    2013-04-01

    which cells in the mammary epithelium continuously interact with cells in the surrounding microenvironment. When the microenvironment receives signals...from cells in the mammary epithelium , it sends back cues that help to maintain normal mammary tissue functions. If these interactions are disturbed...targeting activity, Mol. Cancer Ther., 2004, 3(11), 1365–1373. 5 J. Debnath and J. S. Brugge, Modelling glandular epithelial cancers in three

  6. Suppression of FOXQ1 in benzyl isothiocyanate-mediated inhibition of epithelial-mesenchymal transition in human breast cancer cells.

    Science.gov (United States)

    Sehrawat, Anuradha; Kim, Su-Hyeong; Vogt, Andreas; Singh, Shivendra V

    2013-04-01

    We showed previously that breast cancer chemoprevention with benzyl isothiocyanate (BITC) in MMTV-neu mice was associated with induction of E-cadherin protein in vivo. Loss of E-cadherin expression and induction of mesenchymal markers (e.g. vimentin) are biochemical hallmarks of epithelial-mesenchymal transition (EMT), a developmental process implicated in progression of cancer to aggressive state. This study offers novel insights into the mechanism by which BITC inhibits EMT. Exposure of MDA-MB-231, SUM159 and MDA-MB-468 human breast cancer cells to BITC (2.5 and 5 µM) resulted in transcriptional repression of urokinase-type plasminogen activator (uPA) as well as its receptor (uPAR). However, ectopic expression of uPAR in MDA-MB-468 cells failed to confer protection against induction of E-cadherin and inhibition of cell invasion/migration resulting from BITC treatment. The BITC-mediated induction of E-cadherin and inhibition of cell migration was sustained in MDA-MB-231 and SUM159 cells transiently transfected with an uPAR-targeted small interfering RNA. Overexpression of Forkhead Box Q1 (FOXQ1), whose protein and messenger RNA levels were decreased by BITC treatment in cells and MDA-MB-231 xenografts, conferred marked protection against BITC-mediated inhibition of EMT and cell migration. In conclusion, this study implicates FOXQ1 suppression in BITC-mediated inhibition of EMT in human breast cancer cells.

  7. 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 ...

  8. The function of breast cancer resistance protein in epithelial barriers, stem cells and milk secretion of drugs and xenotoxins.

    Science.gov (United States)

    van Herwaarden, Antonius E; Schinkel, Alfred H

    2006-01-01

    The breast cancer resistance protein [BCRP (also known as ABCG2)] belongs to the ATP binding cassette (ABC) family of transmembrane drug transporters. BCRP has a broad substrate specificity and actively extrudes a wide variety of drugs, carcinogens and dietary toxins from cells. Situated in the apical plasma membrane of epithelial cells of the small and large intestine and renal proximal tubules and in the bile canalicular membrane of hepatocytes, BCRP decreases the oral availability and systemic exposure of its substrates. In several blood-tissue barriers BCRP reduces tissue penetration of its substrates and it protects haematopoietic stem cells from cytotoxic substrates. Moreover, BCRP is expressed in mammary gland alveolar epithelial cells during pregnancy and lactation, where it actively secretes a variety of drugs, toxins and carcinogens into milk. In apparent contradiction with the detoxifying role of BCRP in mothers, this contamination of milk exposes suckling infants and dairy consumers to xenotoxins. BCRP thus affects many important aspects of pharmacology and toxicology.

  9. The role of maintenance proteins in the preservation of epithelial cell identity during mammary gland remodeling and breast cancer initiation

    Institute of Scientific and Technical Information of China (English)

    Danila Coradini; Saro Oriana

    2014-01-01

    During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cellidentity. This identity is maintained during cellreplication in a heritable but DNA-independent manner. The preservation of cellidentity is fundamental, especialy when cels must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cellidentity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG) and Polycomb (PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cellidentity, mammary gland remodeling, and breast cancer initiation.

  10. Alterations of EGFR, p53 and PTEN that mimic changes found in basal-like breast cancer promote transformation of human mammary epithelial cells.

    Science.gov (United States)

    Pires, Maira M; Hopkins, Benjamin D; Saal, Lao H; Parsons, Ramon E

    2013-03-01

    Breast cancer can be classified into different molecular subtypes with varying clinical and pathological characteristics. The basal-like breast cancer subtype represents one of the most aggressive and lethal types of breast cancer, and due to poor mechanistic understanding, it lacks targeted therapy. Many basal-like breast cancer patient samples display alterations of established drivers of cancer development, including elevated expression of EGFR, p53 inactivating mutations and loss of expression of the tumor suppressor PTEN; however, their contribution to human basal-like breast cancer pathogenesis remains ill-defined. Using non-transformed human mammary epithelial cells, we set out to determine whether altering EGFR, p53 and PTEN in different combinations could contribute to basal-like breast cancer progression through transformation of cells. Altering PTEN in combination with either p53 or EGFR in contrast to any of the single alterations caused increased growth of transformed colonies in soft agar. Concomitantly modifying all three genes led to the highest rate of cellular proliferation and the greatest degree of anchorage-independent colony formation. Results from our effort to engineer a model of BBC expressing alterations of EGFR, p53 and PTEN suggest that these changes are cooperative and likely play a causal role in basal-like breast cancer pathogenesis. Consideration should be given to targeting EGFR and restoring p53 and PTEN signaling simultaneously as a strategy for treatment of this subtype of breast cancer.

  11. miR-144 functions as a tumor suppressor in breast cancer through inhibiting ZEB1/2-mediated epithelial mesenchymal transition process

    Directory of Open Access Journals (Sweden)

    Pan Y

    2016-10-01

    Full Text Available Yuliang Pan,1,2 Jun Zhang,1 Huiqun Fu,1 Liangfang Shen2 1Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Oncology Radiotherapy, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China Abstract: Breast cancer is the most common cancer in women worldwide. Local invasion, metastasis, and chemotherapy resistance are the obstacles for treatment of breast cancer. In this study, we aim to investigate the role of miR-144 in breast cancer. We demonstrate that the expression of miR-144 is downregulated in breast cancer and cell lines, and lower miR-144 expression is associated with poor differentiation, higher clinical stage, and lymph node metastasis in patients with breast cancer. The rescue of miR-144 expression is able to inhibit the cell proliferation and the ability of cell migration and invasion. In addition, we show that miR-144 can directly target at 3'-untranslation region of zinc finger E-box-binding homeobox 1 and 2, that is, ZEB1 and ZEB2, and regulate their expression at transcriptional and translational levels. Moreover, we also demonstrate that ectopic expression of miR-144 can inhibit the process of epithelial mesenchymal transition in MCF-7 and MDA-MB-231 cells. Thus, we here demonstrate that miR-144 functions as a tumor suppressor in breast cancer at least partly through inhibiting ZEB1/2-mediated epithelial mesenchymal transition process. Our findings indicate that the miR-144-ZEB1/2 signaling could represent a promising therapeutic target for breast cancer treatment. Keywords: breast cancer, miR-144, ZEB1, ZEB2, epithelial mesenchymal transition

  12. 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.

  13. Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

    Science.gov (United States)

    Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

    2017-02-01

    Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of

  14. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    Science.gov (United States)

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  15. Quantitative analysis of promoter methylation in exfoliated epithelial cells isolated from breast milk of healthy women

    OpenAIRE

    Wong, Chung M; Anderton, Douglas L.; Smith-Schneider, Sallie; Wing, Megan A; Greven, Melissa C; Arcaro, Kathleen F.

    2010-01-01

    Promoter methylation analysis of genes frequently silenced in breast cancer is a promising indicator of breast cancer risk, as these methylation events are thought to occur long before presentation of disease. The numerous exfoliated epithelial cells present in breast milk may provide the breast epithelial DNA needed for detailed methylation analysis and assessment of breast cancer risk. Fresh breast milk samples and health, lifestyle and reproductive history questionnaires were collected fro...

  16. A transcriptional repressive role for epithelial-specific ETS factor ELF3 on oestrogen receptor alpha in breast cancer cells.

    Science.gov (United States)

    Gajulapalli, Vijaya Narasihma Reddy; Samanthapudi, Venkata Subramanyam Kumar; Pulaganti, Madhusudana; Khumukcham, Saratchandra Singh; Malisetty, Vijaya Lakhsmi; Guruprasad, Lalitha; Chitta, Suresh Kumar; Manavathi, Bramanandam

    2016-04-15

    Oestrogen receptor-α (ERα) is a ligand-dependent transcription factor that primarily mediates oestrogen (E2)-dependent gene transcription required for mammary gland development. Coregulators critically regulate ERα transcription functions by directly interacting with it. In the present study, we report that ELF3, an epithelial-specific ETS transcription factor, acts as a transcriptional repressor of ERα. Co-immunoprecipitation (Co-IP) analysis demonstrated that ELF3 strongly binds to ERα in the absence of E2, but ELF3 dissociation occurs upon E2 treatment in a dose- and time-dependent manner suggesting that E2 negatively influences such interaction. Domain mapping studies further revealed that the ETS (E-twenty six) domain of ELF3 interacts with the DNA binding domain of ERα. Accordingly, ELF3 inhibited ERα's DNA binding activity by preventing receptor dimerization, partly explaining the mechanism by which ELF3 represses ERα transcriptional activity. Ectopic expression of ELF3 decreases ERα transcriptional activity as demonstrated by oestrogen response elements (ERE)-luciferase reporter assay or by endogenous ERα target genes. Conversely ELF3 knockdown increases ERα transcriptional activity. Consistent with these results, ELF3 ectopic expression decreases E2-dependent MCF7 cell proliferation whereas ELF3 knockdown increases it. We also found that E2 induces ELF3 expression in MCF7 cells suggesting a negative feedback regulation of ERα signalling in breast cancer cells. A small peptide sequence of ELF3 derived through functional interaction between ERα and ELF3 could inhibit DNA binding activity of ERα and breast cancer cell growth. These findings demonstrate that ELF3 is a novel transcriptional repressor of ERα in breast cancer cells. Peptide interaction studies further represent a novel therapeutic option in breast cancer therapy.

  17. Pterostilbene inhibits triple-negative breast cancer metastasis via inducing microRNA-205 expression and negatively modulates epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Su, Chih-Ming; Lee, Wei-Hwa; Wu, Alexander T H; Lin, Yen-Kuang; Wang, Liang-Shun; Wu, Chih-Hsiung; Yeh, Chi-Tai

    2015-06-01

    Breast cancer is the leading cause of cancer-related deaths among females in economically developing countries. Greater than 95% of breast malignancies are of epithelial origin; the induction of epithelial-to-mesenchymal transition (EMT) has been shown to initiate the metastatic process in breast carcinoma and remains the key target for drug development. Here, we examine the anti-metastatic potential of pterostilbene in modulating EMT process in breast cancer cells both in vitro and in vivo. The differential invasive ability among MCF7, Hs578t and MDA-MB-231 breast cancer cell lines were closely correlated with the expression of EMT markers, determined by Western blots and Matrigel-coated transwells assay. Pterostilbene inhibited the migratory and invasive potential of triple-negative MDA-MB-231 and Hs578t cells, accompanied by the up-regulation of E-cadherin and down-regulation of Snail, Slug, vimentin and ZEB1. Mechanistic investigations revealed a significant up-regulation of miR-205, which resulted in the reduction of Src expression in pterostilbene-treated breast cancer cells. Importantly, pterostilbene suppressed tumor growth and metastasis in MDA-MB-231-bearing NOD/SCID mice by reducing Src/Fak signaling; this observation was consistent with the negative correlations between miR-205 and Src expression in both normal and malignant breast tissues. Our findings provide supports for the usage of pterostilbene as an inhibitor of EMT process and potential candidate for adjuvant therapy.

  18. Epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.

    Directory of Open Access Journals (Sweden)

    Cristiana Angelucci

    Full Text Available Interactions occurring between malignant cells and the stromal microenvironment heavily influence tumor progression. We investigated whether this cross-talk affects some molecular and functional aspects specifically correlated with the invasive phenotype of breast tumor cells (i.e. adhesion molecule expression, membrane fluidity, migration by co-culturing mammary cancer cells exhibiting different degrees of metastatic potential (MDA-MB-231>MCF-7 with fibroblasts isolated from breast healthy skin (normal fibroblasts, NFs or from breast tumor stroma (cancer-associated fibroblasts, CAFs in 2D or 3D (nodules cultures. Confocal immunofluorescence analysis of the epithelial adhesion molecule E-cadherin on frozen nodule sections demonstrated that NFs and CAFs, respectively, induced or inhibited its expression in MCF-7 cells. An increase in the mesenchymal adhesion protein N-cadherin was observed in CAFs, but not in NFs, as a result of the interaction with both kinds of cancer cells. CAFs, in turn, promoted N-cadherin up-regulation in MDA-MB-231 cells and its de novo expression in MCF-7 cells. Beyond promotion of "cadherin switching", another sign of the CAF-triggered epithelial-mesenchymal transition (EMT was the induction of vimentin expression in MCF-7 cells. Plasma membrane labeling of monolayer cultures with the fluorescent probe Laurdan showed an enhancement of the membrane fluidity in cancer cells co-cultured with NFs or CAFs. An increase in lipid packing density of fibroblast membranes was promoted by MCF-7 cells. Time-lapsed cell tracking analysis of mammary cancer cells co-cultured with NFs or CAFs revealed an enhancement of tumor cell migration velocity, even with a marked increase in the directness induced by CAFs.Our results demonstrate a reciprocal influence of mammary cancer and fibroblasts on various adhesiveness/invasiveness features. Notably, CAFs' ability to promote EMT, reduction of cell adhesion, increase in membrane fluidity, and

  19. Sclerotium rolfsii Lectin Induces Stronger Inhibition of Proliferation in Human Breast Cancer Cells than Normal Human Mammary Epithelial Cells by Induction of Cell Apoptosis

    Science.gov (United States)

    Savanur, Mohammed Azharuddin; Eligar, Sachin M.; Pujari, Radha; Chen, Chen; Mahajan, Pravin; Borges, Anita; Shastry, Padma; Ingle, Arvind.; Kalraiya, Rajiv D.; Swamy, Bale M.; Rhodes, Jonathan M.; Yu, Lu-Gang; Inamdar, Shashikala R.

    2014-01-01

    Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. As a lectin that binds specifically to a cancer-associated glycan, has potential to be developed as an anti-cancer agent. PMID:25364905

  20. Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis.

    Science.gov (United States)

    Savanur, Mohammed Azharuddin; Eligar, Sachin M; Pujari, Radha; Chen, Chen; Mahajan, Pravin; Borges, Anita; Shastry, Padma; Ingle, Arvind; Kalraiya, Rajiv D; Swamy, Bale M; Rhodes, Jonathan M; Yu, Lu-Gang; Inamdar, Shashikala R

    2014-01-01

    Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. As a lectin that binds specifically to a cancer-associated glycan, has potential to be developed as an anti-cancer agent.

  1. 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. ...

  2. Fusion of CCL21 non-migratory active breast epithelial and breast cancer cells give rise to CCL21 migratory active tumor hybrid cell lines.

    Directory of Open Access Journals (Sweden)

    Benjamin Berndt

    Full Text Available The biological phenomenon of cell fusion has been linked to tumor progression because several data provided evidence that fusion of tumor cells and normal cells gave rise to hybrid cell lines exhibiting novel properties, such as increased metastatogenic capacity and an enhanced drug resistance. Here we investigated M13HS hybrid cell lines, derived from spontaneous fusion events between M13SV1-EGFP-Neo breast epithelial cells exhibiting stem cell characteristics and HS578T-Hyg breast cancer cells, concerning CCL21/CCR7 signaling. Western Blot analysis showed that all cell lines varied in their CCR7 expression levels as well as differed in the induction and kinetics of CCR7 specific signal transduction cascades. Flow cytometry-based calcium measurements revealed that a CCL21 induced calcium influx was solely detected in M13HS hybrid cell lines. Cell migration demonstrated that only M13HS hybrid cell lines, but not parental derivatives, responded to CCL21 stimulation with an increased migratory activity. Knockdown of CCR7 expression by siRNA completely abrogated the CCL21 induced migration of hybrid cell lines indicating the necessity of CCL21/CCR7 signaling. Because the CCL21/CCR7 axis has been linked to metastatic spreading of breast cancer to lymph nodes we conclude from our data that cell fusion could be a mechanism explaining the origin of metastatic cancer (hybrid cells.

  3. Interactions between exosomes from breast cancer cells and primary mammary epithelial cells leads to generation of reactive oxygen species which induce DNA damage response, stabilization of p53 and autophagy in epithelial cells.

    Directory of Open Access Journals (Sweden)

    Sujoy Dutta

    Full Text Available Exosomes are nanovesicles originating from multivesicular bodies and are released by all cell types. They contain proteins, lipids, microRNAs, mRNAs and DNA fragments, which act as mediators of intercellular communications by inducing phenotypic changes in recipient cells. Tumor-derived exosomes have been shown to play critical roles in different stages of tumor development and metastasis of almost all types of cancer. One of the ways by which exosomes affect tumorigenesis is to manipulate the tumor microenvironments to create tumor permissive "niches". Whether breast cancer cell secreted exosomes manipulate epithelial cells of the mammary duct to facilitate tumor development is not known. To address whether and how breast cancer cell secreted exosomes manipulate ductal epithelial cells we studied the interactions between exosomes isolated from conditioned media of 3 different breast cancer cell lines (MDA-MB-231, T47DA18 and MCF7, representing three different types of breast carcinomas, and normal human primary mammary epithelial cells (HMECs. Our studies show that exosomes released by breast cancer cell lines are taken up by HMECs, resulting in the induction of reactive oxygen species (ROS and autophagy. Inhibition of ROS by N-acetyl-L-cysteine (NAC led to abrogation of autophagy. HMEC-exosome interactions also induced the phosphorylation of ATM, H2AX and Chk1 indicating the induction of DNA damage repair (DDR responses. Under these conditions, phosphorylation of p53 at serine 15 was also observed. Both DDR responses and phosphorylation of p53 induced by HMEC-exosome interactions were also inhibited by NAC. Furthermore, exosome induced autophagic HMECs were found to release breast cancer cell growth promoting factors. Taken together, our results suggest novel mechanisms by which breast cancer cell secreted exosomes manipulate HMECs to create a tumor permissive microenvironment.

  4. Interactions between exosomes from breast cancer cells and primary mammary epithelial cells leads to generation of reactive oxygen species which induce DNA damage response, stabilization of p53 and autophagy in epithelial cells.

    Science.gov (United States)

    Dutta, Sujoy; Warshall, Case; Bandyopadhyay, Chirosree; Dutta, Dipanjan; Chandran, Bala

    2014-01-01

    Exosomes are nanovesicles originating from multivesicular bodies and are released by all cell types. They contain proteins, lipids, microRNAs, mRNAs and DNA fragments, which act as mediators of intercellular communications by inducing phenotypic changes in recipient cells. Tumor-derived exosomes have been shown to play critical roles in different stages of tumor development and metastasis of almost all types of cancer. One of the ways by which exosomes affect tumorigenesis is to manipulate the tumor microenvironments to create tumor permissive "niches". Whether breast cancer cell secreted exosomes manipulate epithelial cells of the mammary duct to facilitate tumor development is not known. To address whether and how breast cancer cell secreted exosomes manipulate ductal epithelial cells we studied the interactions between exosomes isolated from conditioned media of 3 different breast cancer cell lines (MDA-MB-231, T47DA18 and MCF7), representing three different types of breast carcinomas, and normal human primary mammary epithelial cells (HMECs). Our studies show that exosomes released by breast cancer cell lines are taken up by HMECs, resulting in the induction of reactive oxygen species (ROS) and autophagy. Inhibition of ROS by N-acetyl-L-cysteine (NAC) led to abrogation of autophagy. HMEC-exosome interactions also induced the phosphorylation of ATM, H2AX and Chk1 indicating the induction of DNA damage repair (DDR) responses. Under these conditions, phosphorylation of p53 at serine 15 was also observed. Both DDR responses and phosphorylation of p53 induced by HMEC-exosome interactions were also inhibited by NAC. Furthermore, exosome induced autophagic HMECs were found to release breast cancer cell growth promoting factors. Taken together, our results suggest novel mechanisms by which breast cancer cell secreted exosomes manipulate HMECs to create a tumor permissive microenvironment.

  5. 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 ...

  6. Discoidin domain receptor 2 (DDR2) promotes breast cancer cell metastasis and the mechanism implicates epithelial-mesenchymal transition programme under hypoxia.

    Science.gov (United States)

    Ren, Tingting; Zhang, Wei; Liu, Xinping; Zhao, Hu; Zhang, Jian; Zhang, Jing; Li, Xia; Zhang, Yan; Bu, Xin; Shi, Man; Yao, Libo; Su, Jin

    2014-12-01

    A wide range of genes involved in breast cancer metastasis have been reported to be related to the microenvironment. We studied the role of discoidin domain receptor 2 (DDR2), a collagen-binding receptor, in breast cancer progression under hypoxic conditions. We showed that DDR2 protein expression closely correlated with the expression of hypoxic marker HIF-1α in clinical breast cancer specimens. The in vitro data demonstrated that hypoxia treatment increased the levels of both expression and phosphorylation of DDR2 in human breast cancer cell lines. In vivo, orthotopic breast tumour xenografts with DDR2 knockdown displayed reduced dissemination and significant prevention in pulmonary and lymphatic metastasis; conversely, these processes were significantly facilitated by the enforced expression of the activated form of DDR2. Further mechanism studies indicated that DDR2 plays an indispensable role in a series of hypoxia-induced behaviours of breast cancer cells, including migration, invasion, and epithelial-mesenchymal transition (EMT). The transcription factor Snail was found to mediate DDR2-induced down-regulation of the cell-cell adhesion molecule E-cadherin. It was also documented that there is a correlation between DDR2 and E-cadherin expression with the presence of lymph node metastases in 160 cases of invasive human breast carcinoma. In addition, we provided evidence that DDR2 silencing in breast cancer cells prevents the hypoxia-induced activation of ERK MAPK, suggesting its potential involvement in mediating the effect of DDR2 on hypoxia-induced signalling. Based on the results of this study, we conclude that DDR2 participates in hypoxia-induced breast cancer metastasis through the regulation of cell migration, invasion, and EMT, and thus may serve as an accessible therapeutic target for the treatment of breast cancer.

  7. Roles of Breast Cancer Susceptibility Genes BRCA’s in Mammary Epithelial Cell Differentiation

    Science.gov (United States)

    2006-03-01

    associated factor 3 - 3.0 IFNAR1 AA133989 interferon (alpha, beta and omega) receptor 1 -3.1 PDXK AW449022 pyridoxal ( pyridoxine , vitamin B6...IFNAR1 AA133989 Interferon (, , and ) receptor 1 3.1 PDXK AW449022 Pyridoxal ( pyridoxine , vitamin B6) kinase 4.0 HTATIP2 BC002439 HIV-1 Tat...evaluate the risk of breast cancer. N Engl J Med 336, 1409-1415. 26 Cullmann, G., Fien, K., Kobayashi, R., and Stillman, B. (1995). Characterization

  8. Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells

    Directory of Open Access Journals (Sweden)

    Li Qianqian

    2010-10-01

    Full Text Available Abstract Background Spontaneous immortalisation of cultured mammary epithelial cells (MECs is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs and the changes in gene expression associated with BME65Cs cells. Results BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line. In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a. Conclusions Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and

  9. Effect of nanostructured TiO2 crystal phase on photoinduced apoptosis of breast cancer epithelial cells

    Directory of Open Access Journals (Sweden)

    Lagopati N

    2014-07-01

    Full Text Available Nefeli Lagopati,1,2 Effie-Photini Tsilibary,1,* Polycarpos Falaras,2,* Panagiota Papazafiri,3 Evangelia A Pavlatou,4 Eleni Kotsopoulou,1 Paraskevi Kitsiou1,* 1Institute of Biosciences and Applications, 2Institute of Advanced Materials, Physicochemical Processes, Nanotechnology and Microsystems, National Center for Scientific Research “Demokritos”, Athens, Greece; 3Department of Animal and Human Physiology, Faculty of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece; 4Laboratory of General Chemistry, School of Chemical Engineering, National Technical University of Athens, Athens, Greece *These authors contributed equally to this work Purpose: The use of nanoparticles has seen exponential growth in the area of health care, due to the unique physicochemical properties of nanomaterials that make them desirable for medical applications. The aim of this study was to examine the effects of crystal phase-nanostructured titanium dioxide particles on bioactivity/cytotoxicity in breast cancer epithelial cells. Materials and methods: Cultured Michigan Cancer Foundation (MCF-7 and human breast adenocarcinoma (MDA-MB-468 breast cancer epithelial cells were exposed to ultraviolet A light (wavelength 350 nm for 20 minutes in the presence of aqueous dispersions of two different nanostructured titanium dioxide (TiO2 crystal phases: anatase and an anatase–rutile mixture. Detailed characterization of each titanium dispersion was performed by dynamic light scattering. A 3-(4,5-dimethylthiazol-2-yl-2,5 diphenyltetrazolium bromide (MTT colorimetric assay was employed to estimate the percentage of viable cells after each treatment. Western blot analysis of protein expression and characterization, as well as a deoxyribonucleic acid (DNA-laddering assay, were used to detect cell apoptosis. Results: Our results documented that 100% anatase TiO2 nanoparticles (110–130 nm exhibited significantly higher cytotoxicity in

  10. 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).

  11. 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, ...

  12. The role of maintenance proteins in the preservation of epithelial cell identity during mammary gland remodeling and breast cancer initiation.

    Science.gov (United States)

    Coradini, Danila; Oriana, Saro

    2014-02-01

    During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNA-independent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG) and Polycomb (PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.

  13. Cadmium modulates H-ras expression and caspase-3 apoptotic cell death in breast cancer epithelial MCF-7 cells.

    Science.gov (United States)

    Petanidis, Savvas; Hadzopoulou-Cladaras, Margarita; Salifoglou, Athanasios

    2013-04-01

    Cadmium (Cd) is a well-known metal carcinogen associated with tumor formation and carcinogenesis. It has been shown to induce cancer through various cellular mechanisms involving inhibition of DNA repair, abnormal gene expression, induction of oxidative stress, and triggering apoptosis. It is well-established that the H-ras oncogene is involved in the process of carcinogenesis with direct effects on cellular proliferation and tumorigenesis. Given the biotoxicity of cadmium and its association with carcinogenesis, the effect of that metal ion (Cd(II)) was investigated, in a concentration-dependent fashion, on cell viability, cell proliferation, caspase-3 mediated apoptosis and H-ras gene expression in human breast cancer epithelial MCF-7 cells transfected with the H-ras oncogene (wild type and G12V mutation). The findings show a significant modulation effect of cadmium on H-ras gene expression accompanied by up-regulation of caspase-3-related apoptosis in the concentration range of 100-1000 nΜ cadmium. Concurrently, there is a decrease in MCF-7 proliferation. Collectively, the results a) indicate an interplay of cadmium with H-ras(wt and G12V), with cadmium exhibiting a significant concentration-dependent effect on the modulation of H-ras expression, cell viability and proliferation, and b) project distinctly interwoven roles for both cadmium and H-ras in aberrant physiologies in cancer cells.

  14. Expression of Angiogenesis Regulatory Proteins and Epithelial-Mesenchymal Transition Factors in Platelets of the Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Hui Han

    2014-01-01

    Full Text Available Platelets play a role in tumor angiogenesis and growth and are the main transporters of several angiogenesis regulators. Here, we aimed to determine the levels of angiogenesis regulators and epithelial-mesenchymal transition factors sequestered by circulating platelets in breast cancer patients and age-matched healthy controls. Platelet pellets (PP and platelet-poor plasma (PPP were collected by routine protocols. Vascular endothelial growth factor (VEGF, platelet-derived growth factor BB (PDGF-BB, thrombospondin-1 (TSP-1, platelet factor 4 (PF4, and transforming growth factor-β1 (TGF-β1 were measured by enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF (2.1 pg/106 platelets versus 0.9 pg/106 platelets, P < 0.001, PF4 (21.2 ng/106 platelets versus 10.2 ng/106 platelets, P < 0.001, PDGF-BB (42.9 pg/106 platelets versus 19.1 pg/106 platelets, P < 0.001, and TGF-β1 (15.3 ng/106 platelets versus 4.3 ng/106 platelets, P < 0.001 differed in the PP samples of cancer and control subjects. In addition, protein concentrations were associated with clinical characteristics (P<0.05. Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF-BB, and TGF-β1, suggesting a possible target for early diagnosis. VEGF, PDGF, and TGF-β1 concentrations in platelets may be associated with prognosis.

  15. Transforming growth factor-β1 regulates epithelial-mesenchymal transition in association with cancer stem-like cells in a breast cancer cell line.

    Science.gov (United States)

    Jia, Yongfeng; Wu, Di; Yun, Fen; Shi, Lin; Luo, Nianrong; Liu, Zhiyue; Shi, Yonghong; Sun, Qinnuan; Jiang, Lili; Wang, Shiqi; Du, Maolin

    2014-01-01

    Epithelial-mesenchymal transition (EMT) is associated with altered connection and junctions between cells and changes in abilities of invasion and migration. In this study, we investigated whether SK-BR-3 breast cancer cells induced to undergo EMT exhibit changes in morphological and invasion abilities after Transforming growth factor β1 (TGF-β1) treatment. Serum-deprived SK-BR-3 cells were treated with TGF-β1 (0, 10 ng/mL) for 24 h. The cells morphological changes were observed and imaged using inverted phase contrast microscope. Scratch experiment and invasion experiment were employed to detect changes of invasion ability, cell-flow experiment was used to assess cell cycle, immunohistochemistry technique was used to detect epithelial and mesenchymal markers after the crawling cells were fixed. Our research reveal that SK-BR-3 cells become larger and more messy, the elongated cells extend pseudopodia, the link of the cells became more loosely and cell gap widened after TGF-β1 treatment. SK-BR-3 cells showed faster growing and improved invasion abilities after TGF-β1 treatment, and reduced G1 phase cells proportion in the total number of cells after the conversion, in contrast the S phase cells accounted for the proportion of the total number of cells increased. These findings indicate that TGF-β1-induced EMT in breast cancer cells may be associated with major alterations in morphological and invasion abilities.

  16. 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 ...

  17. Identification of EPSTI1, a novel gene induced by epithelial-stromal interaction in human breast cancer

    DEFF Research Database (Denmark)

    Nielsen, Helga Lind; Rønnov-Jessen, Lone; Villadsen, René

    2002-01-01

    reading frame (ORF) encoding a putative 307-amino-acid protein, and mapped to chromosome 13q13.3. EPSTI1 was highly upregulated in invasive breast carcinomas compared with normal breast. In a tissue mRNA panel the most prominent expression of EPSTI1 was found in placenta. Thus, EPSTI1 is a novel human...... (DD), a transcript representing a novel gene, designated epithelial-stromal interaction 1 (breast) (EPSTI1), was identified. EPSTI1 showed no homology to any known gene, but matched a cluster of expressed-sequence tags (ESTs). The full-length cDNA of 1508 bp was generated by 5'-RACE, included an open...

  18. 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 ...

  19. Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2.

    Science.gov (United States)

    Chakrabarti, Rumela; Hwang, Julie; Andres Blanco, Mario; Wei, Yong; Lukačišin, Martin; Romano, Rose-Anne; Smalley, Kirsten; Liu, Song; Yang, Qifeng; Ibrahim, Toni; Mercatali, Laura; Amadori, Dino; Haffty, Bruce G; Sinha, Satrajit; Kang, Yibin

    2012-11-01

    The epithelial-mesenchymal transition (EMT) is a complex process that occurs during organogenesis and in cancer metastasis. Despite recent progress, the molecular pathways connecting the physiological and pathological functions of EMT need to be better defined. Here we show that the transcription factor Elf5, a key regulator of mammary gland alveologenesis, controls EMT in both mammary gland development and metastasis. We uncovered this role for Elf5 through analyses of Elf5 conditional knockout animals, various in vitro and in vivo models of EMT and metastasis, an MMTV-neu transgenic model of mammary tumour progression and clinical breast cancer samples. Furthermore, we demonstrate that Elf5 suppresses EMT by directly repressing the transcription of Snail2, a master regulator of mammary stem cells and a known inducer of EMT. These findings establish Elf5 not only as a key cell lineage regulator during normal mammary gland development, but also as a suppressor of EMT and metastasis in breast cancer.

  20. Reversibility of epithelial-mesenchymal transition (EMT) induced in breast cancer cells by activation of urokinase receptor-dependent cell signaling.

    Science.gov (United States)

    Jo, Minji; Lester, Robin D; Montel, Valerie; Eastman, Boryana; Takimoto, Shinako; Gonias, Steven L

    2009-08-21

    Hypoxia induces expression of the urokinase receptor (uPAR) and activates uPAR-dependent cell signaling in cancer cells. This process promotes epithelial-mesenchymal transition (EMT). uPAR overexpression in cancer cells also promotes EMT. In this study, we tested whether uPAR may be targeted to reverse cancer cell EMT. When MDA-MB 468 breast cancer cells were cultured in 1% O(2), uPAR expression increased, as anticipated. Cell-cell junctions were disrupted, vimentin expression increased, and E-cadherin was lost from cell surfaces, indicating EMT. Transferring these cells back to 21% O(2) decreased uPAR expression and reversed the signs of EMT. In uPAR-overexpressing MDA-MB 468 cells, EMT was reversed by silencing expression of endogenously produced urokinase-type plasminogen activator (uPA), which is necessary for uPAR-dependent cell signaling, or by targeting uPAR-activated cell signaling factors, including phosphatidylinositol 3-kinase, Src family kinases, and extracellular signal-regulated kinase. MDA-MB 231 breast cancer cells express high levels of uPA and uPAR and demonstrate mesenchymal cell morphology under normoxic culture conditions (21% O(2)). Silencing uPA expression in MDA-MB-231 cells decreased expression of vimentin and Snail, and induced changes in morphology characteristic of epithelial cells. These results demonstrate that uPAR-initiated cell signaling may be targeted to reverse EMT in cancer.

  1. Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway.

    Science.gov (United States)

    Han, Dan; Wu, Gang; Chang, Chan; Zhu, Fang; Xiao, Yin; Li, Qiuhui; Zhang, Tao; Zhang, Liling

    2015-12-01

    Disulfiram (DSF), an anti-alcoholism drug, has been reported as an inhibitor of NF-κB. NF-κB is involved in epithelial-mesenchymal transition (EMT) and self-renewal of breast cancer stem cells (CSCs). In this study, we treated MCF-7 and MDA-MB-231 breast cancer cells with TGF-β to induce EMT and cancer stem-like features and studied whether DSF can reverse this process. We found that DSF inhibited TGF-β induced EMT in breast cancer cells in a dose-dependent manner. Also, DSF inhibited EMT-associated stem-like features, migration and invasion of tumor cells as well as tumor growth in xenograft model. The activation of NF-κB was linked with EMT and stem-like cells. We conclude that DSF can suppress NF-κB activity and downregulate ERK/NF-κB/Snail pathway, leading to reverse EMT and stem-like features. Our data suggest that DSF inhibits EMT and stem-like properties in breast cancer cells associated with inhibition of the ERK/NF-κB/Snail pathway.

  2. The monoamine oxidase-A inhibitor clorgyline promotes a mesenchymal-to-epithelial transition in the MDA-MB-231 breast cancer cell line.

    Science.gov (United States)

    Satram-Maharaj, Tamara; Nyarko, Jennifer N K; Kuski, Kelly; Fehr, Kelsey; Pennington, Paul R; Truitt, Luke; Freywald, Andrew; Lukong, Kiven Erique; Anderson, Deborah H; Mousseau, Darrell D

    2014-12-01

    Monoamine oxidase-A (MAO-A) dysfunction has been historically associated with depression. Recently, depression as well as altered MAO-A expression have both been associated with a poor prognosis in cancers, although the mechanism involved remains ambiguous. For example, MAO-A mRNA is repressed across cancers, yet MAO-A protein and levels of serotonin, a substrate of MAO-A implicated in depression, are paradoxically increased in malignancies, including breast cancer. The effect of clorgyline (CLG), a selective inhibitor of MAO-A, on malignant behaviour, expression of transitional markers, and biochemical correlates was examined in two human breast carcinoma cell lines, i.e. the epithelial, oestrogen receptor (ER)-positive MCF-7 cell line and the post-EMT (mesenchymal), ER-negative MDA-MB-231 cell line. CLG exerted little effect on malignant behaviour in MCF-7 cells, but inhibited proliferation and anchorage-independent growth, and increased invasiveness and active migration of MDA-MB-231 cells. CLG induced the expression of the mesenchymal marker vimentin in MCF-7 cells, but not in MDA-MB-231 cells. In contrast, CLG induced the epithelial protein marker E-cadherin in both cell lines, with a more robust effect in MDA-MB-231 cells (where a nuclear E-cadherin signal was also detected). This effect appears to be independent of any canonical Snai1-mediated regulation of E-cadherin mRNA expression. CLG interfered with the β-catenin/[phospho]GSK-3β complex as well as the E-cadherin/β-catenin complex in both cell lines cells, but, again, the effect was more robust in MDA-MB-231 cells. Parallel studies revealed a general lack of effect of CLG on the ER-negative, epithelial Au565 breast cancer cell line. Thus, any effect of CLG on metastatic behaviours appears to rely on the cell's EMT status rather than on the cell's ER status. These data suggest that inactivation of MAO-A triggers a mesenchymal-to-epithelial transition in MDA-MB-231 cells via a non-canonical mechanism

  3. 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 ...

  4. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers

    NARCIS (Netherlands)

    Beesley, J.; Pickett, H.A.; Johnatty, S.E.; Dunning, A.M.; Chen, X.; Li, J.; Michailidou, K.; Lu, Y.; Rider, D.N.; Palmieri, R.T.; Stutz, M.D.; Lambrechts, D.; Despierre, E.; Lambrechts, S.; Vergote, I.; Chang-Claude, J.; Nickels, S.; Vrieling, A.; Flesch-Janys, D.; Wang-Gohrke, S.; Eilber, U.; Bogdanova, N.; Antonenkova, N.; Runnebaum, I.B.; Dork, T.; Goodman, M.T.; Lurie, G.; Wilkens, L.R.; Matsuno, R.K.; Kiemeney, L.A.L.M.; Aben, K.K.H.; Marees, T.; Massuger, L.F.A.G.; Fridley, B.L.; Vierkant, R.A.; Bandera, E.V.; Olson, S.H.; Orlow, I.; Rodriguez-Rodriguez, L.; Cook, L.S.; Le, N.D.; Brooks-Wilson, A.; Kelemen, L.E.; Campbell, I.; Gayther, S.A.; Ramus, S.J.; Gentry-Maharaj, A.; Menon, U.; Ahmed, S.; Baynes, C.; Pharoah, P.D.; Muir, K.; Lophatananon, A.; Chaiwerawattana, A.; Wiangnon, S.; MacGregor, S.; Easton, D.F.; Reddel, R.R.; Goode, E.L.; Chenevix-Trench, G.

    2011-01-01

    Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC). We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP) within the TERT p

  5. Elucidation of epithelial-mesenchymal transition-related pathways in a triple-negative breast cancer cell line model by multi-omics interactome analysis.

    Science.gov (United States)

    Pauling, Josch K; Christensen, Anne G; Batra, Richa; Alcaraz, Nicolas; Barbosa, Eudes; Larsen, Martin R; Beck, Hans C; Leth-Larsen, Rikke; Azevedo, Vasco; Ditzel, Henrik J; Baumbach, Jan

    2014-11-01

    In life sciences, and particularly biomedical research, linking aberrant pathways exhibiting phenotype-specific alterations to the underlying physical condition or disease is an ongoing challenge. Computationally, a key approach for pathway identification is data enrichment, combined with generation of biological networks. This allows identification of intrinsic patterns in the data and their linkage to a specific context such as cellular compartments, diseases or functions. Identification of aberrant pathways by traditional approaches is often limited to biological networks based on either gene expression, protein expression or post-translational modifications. To overcome single omics analysis, we developed a set of computational methods that allow a combined analysis of data collections from multiple omics fields utilizing hybrid interactome networks. We apply these methods to data obtained from a triple-negative breast cancer cell line model, combining data sets of gene and protein expression as well as protein phosphorylation. We focus on alterations associated with the phenotypical differences arising from epithelial-mesenchymal transition in two breast cancer cell lines exhibiting epithelial-like and mesenchymal-like morphology, respectively. Here we identified altered protein signaling activity in a complex biologically relevant network, related to focal adhesion and migration of breast cancer cells. We found dysregulated functional network modules revealing altered phosphorylation-dependent activity in concordance with the phenotypic traits and migrating potential of the tested model. In addition, we identified Ser267 on zyxin, a protein coupled to actin filament polymerization, as a potential in vivo phosphorylation target of cyclin-dependent kinase 1.

  6. An Epithelial-Derived, Integral Membrane, Kunitz-Type Serine Protease Inhibitor in Breast Cancer

    Science.gov (United States)

    2005-08-01

    an epithelial membrane serine protease. J Biol Chein 275: 36720-36725, 2000. prevents15. Lin CY, Anders J, Johnson M, and Dickson RB. Purification and...functions properly, thus trypsin-like activity. J Biol Chein 274: 18231--18236, 1999. 0 avoiding harmful effects. 17. Lin CY, Wang JK, Torri J, Dou L, Sang

  7. 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.

  8. Combined niclosamide with cisplatin inhibits epithelial-mesenchymal transition and tumor growth in cisplatin-resistant triple-negative breast cancer.

    Science.gov (United States)

    Liu, Junjun; Chen, Xiaosong; Ward, Toby; Pegram, Mark; Shen, Kunwei

    2016-07-01

    Women with triple-negative breast cancer have worse prognosis compared to other breast cancer subtypes. Acquired drug resistance remains to be an important reason influencing triple-negative breast cancer treatment efficacy. A prevailing theory postulates that the cancer resistance and recurrence results from a subpopulation of tumor cells with stemness program, which are often insensitive to cytotoxic drugs such as cisplatin. Recent studies suggested that niclosamide, an anti-helminthic drug, has potential therapeutic activities against breast cancer stem cells, which prompts us to determine its roles on eliminating cisplatin-resistant cancer cells. Hence, we established a stable cisplatin-resistant MDA-MB-231 cell line (231-CR) through continuously exposure to increasing concentrations of cisplatin (5-20 μmol/l). Interestingly, 231-CR exhibited properties associated to epithelial-mesenchymal transition with enhanced invasion, preserved proliferation, increased mammosphere formation, and reduced apoptosis compared to naive MDA-MB-231 sensitive cells (231-CS). Importantly, niclosamide or combination with cisplatin inhibited both 231-CS and 231-CR cell proliferation in vitro. In addition, niclosamide reversed the EMT phenotype of 231-CR by downregulation of snail and vimentin. Mechanistically, niclosamide treatment in combination with or without cisplatin significantly inhibited Akt, ERK, and Src signaling pathways. In vivo study showed that niclosamide or combination with cisplatin could repress the growth of xenografts originated from either 231-CS or 231-CR cells, with prominent suppression of Ki67 expression. These findings suggested that niclosamide might serve as a novel therapeutic strategy, either alone or in combination with cisplatin, for triple-negative breast cancer treatment, especially those resistant to cisplatin.

  9. Kaempferol, a phytoestrogen, suppressed triclosan-induced epithelial-mesenchymal transition and metastatic-related behaviors of MCF-7 breast cancer cells.

    Science.gov (United States)

    Lee, Geum-A; Choi, Kyung-Chul; Hwang, Kyung-A

    2017-01-01

    As a phytoestrogen, kaempferol is known to play a chemopreventive role inhibiting carcinogenesis and cancer progression. In this study, the influences of triclosan, an anti-bacterial agent recently known for an endocrine disrupting chemical (EDC), and kaempferol on breast cancer progression were examined by measuring their effects on epithelial-mesenchymal transition (EMT) and metastatic-related behaviors of MCF-7 breast cancer cells. Morphological changes of MCF-7 cells were observed, and a wound-healing assay was performed after the treatment of triclosan and kaempferol. The effects of triclosan and kaempferol on protein expression of EMT-related markers such as E-cadherin, N-cadherin, Snail, and Slug and metastasis-related markers such as cathepsin B, D, MMP-2 and -9 were investigated by Western blot assay. In microscopic observations, triclosan (10(-6)M) or E2 (10(-9)M) induced transition to mesenchymal phenotype of MCF-7 cells compared with the control. Co-treatment of ICI 182,780 (10(-8)M), an ER antagonist, or kaempferol (25μM) with E2 or triclosan restored the cellular morphology to an epithelial phenotype. In a wound-healing scratch and a transwell migration assay, triclosan enhanced migration and invasion of MCF-7 cells, but co-treatment of kaempferol or ICI 182,780 reduced the migration and invasion ability of MCF-7 cells to the control level. In addition, kaempferol effectively suppressed E2 or triclosan-induced protein expressions of EMT and metastasis promoting markers. Taken together, triclosan may be a distinct xenoestrogenic EDC to promote EMT, migration, and invasion of MCF-7 breast cancer cells through ER. On the other hand, kaempferol can be an alternative chemopreventive agent to effectively suppress the metastatic behavior of breast cancer induced by an endogenous estrogen as well as exogenous xenoestrogenic compounds including triclosan.

  10. Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

    Science.gov (United States)

    Bussard, Karen M; Smith, Gilbert H

    2012-01-01

    Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

  11. Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

    Directory of Open Access Journals (Sweden)

    Karen M Bussard

    Full Text Available Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

  12. 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 ...

  13. Expression of Proteins Involved in Epithelial-Mesenchymal Transition as Predictors of Metastasis and Survival in Breast Cancer Patients

    Science.gov (United States)

    2015-01-01

    biology of metastasis could lead to better stratification of recurrence risk. We proposed to study genes related to epithelial-mesenchymal transition (EMT...pathologist at RPCI and a breast biology researcher at the University at Buffalo (Dr. Patricia Masso-Welch) to identify and implement an appropriate plan for...Abstract nr 3593. DOI:1538-7445.AM2012-3593. iv. Roberts MR, Sucheston- Campbell LE, Zirpoli GR, Bandera EV, Ambrosone CB, and Yao S. Single nucleotide

  14. 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.

  15. Differential gene expression pattern in human mammary epithelial cells induced by realistic organochlorine mixtures described in healthy women and in women diagnosed with breast cancer.

    Science.gov (United States)

    Rivero, Javier; Henríquez-Hernández, Luis Alberto; Luzardo, Octavio P; Pestano, José; Zumbado, Manuel; Boada, Luis D; Valerón, Pilar F

    2016-03-30

    Organochlorine pesticides (OCs) have been associated with breast cancer development and progression, but the mechanisms underlying this phenomenon are not well known. In this work, we evaluated the effects exerted on normal human mammary epithelial cells (HMEC) by the OC mixtures most frequently detected in healthy women (H-mixture) and in women diagnosed with breast cancer (BC-mixture), as identified in a previous case-control study developed in Spain. Cytotoxicity and gene expression profile of human kinases (n=68) and non-kinases (n=26) were tested at concentrations similar to those described in the serum of those cases and controls. Although both mixtures caused a down-regulation of genes involved in the ATP binding process, our results clearly indicate that both mixtures may exert a very different effect on the gene expression profile of HMEC. Thus, while BC-mixture up-regulated the expression of oncogenes associated to breast cancer (GFRA1 and BHLHB8), the H-mixture down-regulated the expression of tumor suppressor genes (EPHA4 and EPHB2). Our results indicate that the composition of the OC mixture could play a role in the initiation processes of breast cancer. In addition, the present results suggest that subtle changes in the composition and levels of pollutants involved in environmentally relevant mixtures might induce very different biological effects, which explain, at least partially, why some mixtures seem to be more carcinogenic than others. Nonetheless, our findings confirm that environmentally relevant pollutants may modulate the expression of genes closely related to carcinogenic processes in the breast, reinforcing the role exerted by environment in the regulation of genes involved in breast carcinogenesis.

  16. Phenformin Induces Cell Cycle Change, Apoptosis, and Mesenchymal-Epithelial Transition and Regulates the AMPK/mTOR/p70s6k and MAPK/ERK Pathways in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Zhao Liu

    Full Text Available Breast cancer remains a world-wide challenge, and additional anti-cancer therapies are still urgently needed. Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin. However, little attention has been given to the role of phenformin in breast cancer. In this study, we reveal the role of phenformin in cell death of the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 breast cancer cell lines. The respective IC50 values of phenformin in MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error. Phenformin induced cell cycle change and apoptosis in breast cancer cells via the AMPK/mTOR/p70s6k and MAPK/ERK pathways. Interestingly, phenformin induced MET (mesenchymal-epithelial transition and decreased the migration rate in breast cancer cell lines. Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice. Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer.

  17. Phenformin Induces Cell Cycle Change, Apoptosis, and Mesenchymal-Epithelial Transition and Regulates the AMPK/mTOR/p70s6k and MAPK/ERK Pathways in Breast Cancer Cells.

    Science.gov (United States)

    Liu, Zhao; Ren, Lidong; Liu, Chenghao; Xia, Tiansong; Zha, Xiaoming; Wang, Shui

    2015-01-01

    Breast cancer remains a world-wide challenge, and additional anti-cancer therapies are still urgently needed. Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin. However, little attention has been given to the role of phenformin in breast cancer. In this study, we reveal the role of phenformin in cell death of the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 breast cancer cell lines. The respective IC50 values of phenformin in MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error). Phenformin induced cell cycle change and apoptosis in breast cancer cells via the AMPK/mTOR/p70s6k and MAPK/ERK pathways. Interestingly, phenformin induced MET (mesenchymal-epithelial transition) and decreased the migration rate in breast cancer cell lines. Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice. Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer.

  18. 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.

  19. Overexpression of SDF-1 activates the NF-κB pathway to induce epithelial to mesenchymal transition and cancer stem cell-like phenotypes of breast cancer cells.

    Science.gov (United States)

    Kong, Lingxin; Guo, Sufen; Liu, Chunfeng; Zhao, Yiling; Feng, Chong; Liu, Yunshuang; Wang, Tao; Li, Caijuan

    2016-03-01

    The formation of EMT and EMT-induced CSC-like phenotype is crucial for the metastasis of tumor cells. The stromal cell-derived factor-1 (SDF-1) is upregulated in various human carcinomas, which is closely associated with proliferation, migration, invasion and prognosis of malignancies. However, limited attention has been directed towards the effect of SDF-1 on epithelial to mesenchymal transition (EMT) or cancer stem cell (CSC)-like phenotype formation in breast cancer cells and the related mechanism. In the present study, we screened MCF-7 cells with low SDF-1 expression level for the purpose of evaluating whether SDF-1 is involved in EMT and CSC-like phenotype formation in MCF-7 cells. The pEGFP-N1-SDF-1 plasmid was transfected into MCF-7 cells, and the stably overexpressed SDF-1 in MCF-7 cells was confirmed by real-time PCR and western blot analysis. Colony formation assay, MTT, wound healing assay and Transwell invasion assay demonstrated that overexpression of SDF-1 significantly boosted the proliferation, migration and invasion of MCF-7 cells compared with parental (PSDF-1 overexpressing MCF-7 cells (PSDF-1 overexpressed MCF-7 cells in comparison with parental (PSDF-1 induced the activation of NF-κB pathway in MCF-7 cells. Conversely, suppressing or silencing p65 expression by antagonist or RNA interference could remarkably increase the expression of E-cadherin in SDF-1 overexpressed MCF-7 cells (PSDF-1 enhanced EMT by activating the NF-κB pathway of MCF-7 cells and further induced the formation of CSC-like phenotypes, ultimately promoting the proliferation and metastasis of MCF-7 cells. Therefore, SDF-1 may further be assessed as a potential target for gene therapy of breast cancer.

  20. In vitro methods to culture primary human breast epithelial cells.

    Science.gov (United States)

    Raouf, Afshin; Sun, Yu Jia

    2013-01-01

    Current evidence suggests that much like leukemia, breast tumors are maintained by a small subpopulation of tumor cells that have stem cell properties. These cancer stem cells are envisaged to be responsible for tumor formation and relapse. Therefore, knowledge about their nature will provide a platform to develop therapies to eliminate these breast cancer stem cells. This concept highlights the need to understand the mechanisms that regulate the normal functions of the breast stem cells and their immediate progeny as alterations to these same mechanisms can cause these primitive cells to act as cancer stem cells. The study of the primitive cell functions relies on the ability to isolate them from primary sources of breast tissue. This chapter describes processing of discarded tissue from reduction mammoplasty samples as sources of normal primary human breast epithelial cells and describes cell culture systems to grow single-cell suspensions prepared from these reduction samples in vitro.

  1. 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.

  2. Downregulation of β-catenin decreases the tumorigenicity, but promotes epithelial-mesenchymal transition in breast cancer cells

    OpenAIRE

    Kai Cai; Longwei Jiang; Jing Wang; Hongyi Zhang; Xiaoying Wang; Dengyu Cheng; Jun Dou

    2014-01-01

    Background: Wnt/β-catenin signaling pathway plays a key role in human breast cancer progression. In this study, we down regulated β-catenin expression in human breast cancer MDA-MB-231 cells and investigated the effect of β-catenin knockdown on the cell biological characteristics. Materials and Methods: The recombinant plasmids of pSUPER-enhancement green fluorescent protein 1 (EGFP1)-scrabble-β-catenin-short hairpin ribonucleic acid (shRNA) and pSUPER-EGFP1-β-catenin-shRNA-1 were transfe...

  3. Low Trichorhinophalangeal Syndrome 1 Gene Transcript Levels in Basal-like Breast Cancer Associate with Mesenchymal-to-epithelial Transition

    Institute of Scientific and Technical Information of China (English)

    Yi Bao; Ling-juan Ruan; Juan-fen Mo

    2013-01-01

    Objective To investigate trichorhinophalangeal syndrome 1 gene (TRPS-1) expression patterns in different subtypes of breast cancer and its correlations with other genes and survival using microarray data sets. Methods The transcripts of TRPS-1 and its role in survival in breast cancer were analyzed using published microarray data sets-Netherlands Cancer Institute (NKI) cohort andWang cohort. Results TRPS-1 expression was lower in basal-like breast cancer. The mRNA levels of TRPS-1 negatively correlated with Slug (Pearson correlation coefficient=−0.1366, P=0.0189 in NKI data set and Pearson correlation coefficient=−0.1571, P=0.0078 in Wang data set), FOXC1 (Pearson correlation coefficient=−0.1211, P=0.0376 in NKI data set and Pearson correlation coefficient=−0.1709, P=0.0037 in Wang data set), and CXCL1 (Pearson correlation coefficient=−0.1197, P=0.0399 in NKI data set and Pearson correlation coefficient=−0.3436, P Conclusion The strong expression of TRPS-1 may serve as a good prognostic marker in breast cancer.

  4. 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 ...

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

    Science.gov (United States)

    Zhang, Panshi; Yang, Xiaowei; Yin, Qian; Yi, Jilin; Shen, Wenzhuang; Zhao, Lu; Zhu, Zhi; Liu, Jinwen

    2016-01-01

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

  6. Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

    Science.gov (United States)

    2011-10-01

    analyzed data on tumor progression in these genetically modified animals and completed the staining of different markers of tumor growth (FGF/ FGFR ...H) . Original magnifications: X400 (A-H) 6. FGF, FGFRs and markers differentiating normal and mammary tumor cells We also continued to...oncogene or the absence of FGF2. Figure 5 Immunohistochemistry (IHC) of FGFR in mammary cancer. Staining confirmed the presence of FGFR1

  7. Breast cancer in men

    Science.gov (United States)

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

  8. The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells.

    Science.gov (United States)

    Li, Jin-Ping; Yang, Yin-Xue; Liu, Qi-Lun; Zhou, Zhi-Wei; Pan, Shu-Ting; He, Zhi-Xu; Zhang, Xueji; Yang, Tianxin; Pan, Si-Yuan; Duan, Wei; He, Shu-Ming; Chen, Xiao-Wu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2015-01-01

    Danusertib (Danu) is a pan-inhibitor of Aurora kinases and a third-generation breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (Bcr-Abl) tyrosine kinase inhibitor, but its antitumor effect and underlying mechanisms in the treatment of human breast cancer remain elusive. This study aimed to investigate the effects of Danu on the growth, apoptosis, autophagy, and epithelial-to-mesenchymal transition (EMT) and the molecular mechanisms in human breast cancer MCF7 and MDA-MB-231 cells. The results demonstrated that Danu remarkably inhibited cell proliferation, induced apoptosis and autophagy, and suppressed EMT in both breast cancer cell lines. Danu arrested MCF7 and MDA-MB-231 cells in G2/M phase, accompanied by the downregulation of cyclin-dependent kinase 1 and cyclin B1 and upregulation of p21 Waf1/Cip1, p27 Kip1, and p53. Danu significantly decreased the expression of B-cell lymphoma-extra-large (Bcl-xl) and B-cell lymphoma 2 (Bcl-2), but increased the expression of Bcl-2-associated X protein (Bax) and p53-upregulated modulator of apoptosis (PUMA), and promoted the cleavage of caspases 3 and 9. Furthermore, Danu significantly increased the expression levels of the membrane-bound microtubule-associated protein 1A/1B-light chain 3 (LC3-II) and beclin 1 in breast cancer cells, two markers for autophagy. Danu induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases 1 and 2 (Erk1/2) and inhibited the activation of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways in breast cancer cells. Treatment with wortmannin (a phosphatidylinositol 3-kinase inhibitor) markedly inhibited Danu-induced activation of p38 MAPK and conversion of cytosolic LC3-I to membrane-bound LC3-II. Pharmacological inhibition and small interfering RNA-mediated knockdown of p38 MAPK suppressed Akt activation, resulting in LC3-II accumulation and enhanced autophagy. Pharmacological inhibition

  9. Beta-elemene blocks epithelial-mesenchymal transition in human breast cancer cell line MCF-7 through Smad3-mediated down-regulation of nuclear transcription factors.

    Directory of Open Access Journals (Sweden)

    Xian Zhang

    Full Text Available Epithelial-mesenchymal transition (EMT is the first step required for breast cancer to initiate metastasis. However, the potential of drugs to block and reverse the EMT process are not well explored. In the present study, we investigated the inhibitory effect of beta-elemene (ELE, an active component of a natural plant-derived anti-neoplastic agent in an established EMT model mediated by transforming growth factor-beta1 (TGF-β1. We found that ELE (40 µg/ml blocked the TGF-β1-induced phenotypic transition in the human breast cancer cell line MCF-7. ELE was able to inhibit TGF-β1-mediated upregulation of mRNA and protein expression of nuclear transcription factors (SNAI1, SNAI2, TWIST and SIP1, potentially through decreasing the expression and phosphorylation of Smad3, a central protein mediating the TGF-β1 signalling pathway. These findings suggest a potential therapeutic benefit of ELE in treating basal-like breast cancer.

  10. Histone deacetylase inhibitor entinostat reverses epithelial to mesenchymal transition of breast cancer cells by reversing the repression of E-cadherin.

    Science.gov (United States)

    Shah, Preeti; Gau, Yael; Sabnis, Gauri

    2014-01-01

    Loss of ERα in breast cancer correlates with poor prognosis, increased recurrence rates, and higher incidence of metastasis. Epigenetic silencing of E-cadherin (loss of which is associated with more invasive phenotype) is observed in metastatic cell lines and invasive breast cancers. Here, we are showing that entinostat (ENT) can reverse epithelial to mesenchymal transition (EMT), which is considered to be a first step in the process of metastases formation. Triple-negative breast cancer cells such as MDA-MB-231 and Hs578T show a basal phenotype characterized by loss of E-cadherin expression and higher expression of mesenchymal markers such as N-cadherin and vimentin along with transcriptional repressors such as twist and snail. When MDA-MB-231 and Hs578T cells or tumors were treated with ENT, E-cadherin transcription was increased along with reduction in N-cadherin mRNA expression. Chromatin immunoprecipitation assay showed that treatment of MDA-MB-231 and Hs578T cells increased the activation of E-cadherin promoter by reducing the association of twist and snail with the E-cadherin (CDH1) promoter and downregulated both the snail and twist. ENT also inhibited cell migration in vitro. In addition, phosphorylation of vimentin was increased, as well as remodeling of vimentin filaments. ENT treatment also reduced formation of tubulin-based microtentacles, which help floating cells attach to other surfaces. These findings suggest that ENT can reverse EMT and may reduce the formation of metastasis.

  11. Epithelial-Mesenchymal Transitions and the Expression of Twist in MCF-7/ADR,Human Multidrug-Resistant Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Fei Zhang; Yurong Shi; Lin Zhang; Bin Zhang; Xiyin Wei; Yi Yang; RUi Wang; Ruifang Niu

    2007-01-01

    OBJECTIVE To study the expression levels of Twist and epithelialmesenchymal transitions in multidrug-resistant MCF-7/ADR breast cancer cells,and to study the relationship between multidrug resistance (MDR) and metastatic potential of the cells.METHODS RT-PCR,immunohislochemical and Western blotting methods were used to examine the changes of expression levels of the transcription factor Twist.E-cadherin and N-cadherin in the MCF-7 breast cancer cell line and its multidrug-resistant variant.MCF-7/ADR.RESULTS In MCF-7 cells,the expression of E-cadherin can be detected,but there is no expression of Twisl or N-cadherin.In MCF-7/ADR cells,E-cadherin expression is lost.bul the expression of two other genes was significantly positive.CONCLUSION Epithelial-mesenchymal transitions induced by Twist,may have a relationship with enhanced invasion and metastatic potential during the development of multidrug-resistant MCF-7/ADR breast cancer cells.

  12. 3D models of epithelial-mesenchymal transition in breast cancer metastasis: high-throughput screening assay development, validation, and pilot screen.

    Science.gov (United States)

    Li, Qun; Chen, Chaoyu; Kapadia, Amit; Zhou, Qiong; Harper, Mary Kay; Schaack, Jerome; LaBarbera, Daniel V

    2011-02-01

    Despite advancements in therapies developed for the treatment of cancer, patient prognosis and mortality rates have improved minimally, and metastasis remains the primary cause of cancer mortality worldwide. An underlying mechanism promoting metastasis in many types of cancer is epithelial-mesenchymal transition (EMT). Here the authors report a novel 3D model of EMT and metastatic breast cancer suitable for high-throughput screening (HTS) drug discovery. The primary assay incorporates the expression of the prognostic biomarker vimentin, as a luciferase reporter of EMT, in basil-like/triple-negative MDA-MB-231 breast carcinoma spheroids. Using this model, the authors developed a number of known antitumor agents as control modulators of EMT. U0126, PKC412, PF2341066, dasatinib, and axitinib downregulated vimentin expression by 70% to 90% as compared to untreated spheroids. Counterassays were developed to measure spheroid viability and the invasive potential of MDA-MB-231 spheroids after small-molecule treatment and used to confirm hits from primary screening. Finally, the authors conducted a pilot screen to validate this model for HTS using a purified library of marine secondary metabolites. From 230 compounds screened, they obtained a Z' score of 0.64, indicative of an excellent assay, and confirmed 4 hits, including isonaamidine B, papuamine, mycalolide E, and jaspamide. This HTS model demonstrates the potential to identify small-molecule modulators of EMT that could be used to discover novel antimetastatic agents for the treatment of cancer.

  13. 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.

  14. Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers

    Science.gov (United States)

    2016-09-20

    Colorectal Cancer; Gastric Adenocarcinoma; Esophageal Cancer; Hepatocellular Carcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Ovarian Epithelial Cancer; Carcinoma Breast Stage IV; Hormone-refractory Prostate Cancer; Pancreatic Ductal Adenocarcinoma; Head and Neck Cancers- Squamous Cell; Renal Cell Cancer; Urinary Bladder Neoplasms; Cervical Cancer; Endometrial Cancer; Follicular Thyroid Cancer; Glioblastoma Multiforme

  15. Increased promoter methylation in exfoliated breast epithelial cells in women with a previous breast biopsy.

    Science.gov (United States)

    Browne, Eva P; Punska, Elizabeth C; Lenington, Sarah; Otis, Christopher N; Anderton, Douglas L; Arcaro, Kathleen F

    2011-12-01

    Accurately identifying women at increased risk of developing breast cancer will provide greater opportunity for early detection and prevention. DNA promoter methylation is a promising biomarker for assessing breast cancer risk. Breast milk contains large numbers of exfoliated epithelial cells that are ideal for methylation analyses. Exfoliated epithelial cells were isolated from the milk obtained from each breast of 134 women with a history of a non-proliferative benign breast biopsy (Biopsy Group). Promoter methylation of three tumor suppressor genes, RASSF1, SFRP1 and GSTP1, was assessed by pyrosequencing of bisulfite-modified DNA. Methylation scores from the milk of the 134 women in the Biopsy Group were compared to scores from 102 women for whom a breast biopsy was not a recruitment requirement (Reference Group). Mean methylation scores for RASSF1 and GSTP1 were significantly higher in the Biopsy than in the Reference Group. For all three genes the percentage of outlier scores was greater in the Biopsy than in the Reference Group but reached statistical significance only for GSTP1. A comparison between the biopsied and non-biopsied breasts of the Biopsy Group revealed higher mean methylation and a greater number of outlier scores in the biopsied breast for both SFRP1 and RASSF1, but not for GSTP1. This is the first evidence of CpG island methylation in tumor suppressor genes of women who may be at increased risk of developing breast cancer based on having had a prior breast biopsy.

  16. 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.

  17. 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 ...

  18. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Christopher A Maxwell

    2011-11-01

    Full Text Available Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((wHR = 1.09 (95% CI 1.02-1.16, p(trend = 0.017; and n = 3,965, (wHR = 1.04 (95% CI 0.94-1.16, p(trend = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.

  19. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.

    Science.gov (United States)

    Maxwell, Christopher A; Benítez, Javier; Gómez-Baldó, Laia; Osorio, Ana; Bonifaci, Núria; Fernández-Ramires, Ricardo; Costes, Sylvain V; Guinó, Elisabet; Chen, Helen; Evans, Gareth J R; Mohan, Pooja; Català, Isabel; Petit, Anna; Aguilar, Helena; Villanueva, Alberto; Aytes, Alvaro; Serra-Musach, Jordi; Rennert, Gad; Lejbkowicz, Flavio; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Ripamonti, Carla B; Bonanni, Bernardo; Viel, Alessandra; Allavena, Anna; Bernard, Loris; Radice, Paolo; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Dubrovsky, Maya; Milgrom, Roni; Jakubowska, Anna; Cybulski, Cezary; Gorski, Bohdan; Jaworska, Katarzyna; Durda, Katarzyna; Sukiennicki, Grzegorz; Lubiński, Jan; Shugart, Yin Yao; Domchek, Susan M; Letrero, Richard; Weber, Barbara L; Hogervorst, Frans B L; Rookus, Matti A; Collee, J Margriet; Devilee, Peter; Ligtenberg, Marjolijn J; Luijt, Rob B van der; Aalfs, Cora M; Waisfisz, Quinten; Wijnen, Juul; Roozendaal, Cornelis E P van; Easton, Douglas F; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Harrington, Patricia; Evans, D Gareth; Lalloo, Fiona; Eeles, Rosalind; Izatt, Louise; Chu, Carol; Eccles, Diana; Douglas, Fiona; Brewer, Carole; Nevanlinna, Heli; Heikkinen, Tuomas; Couch, Fergus J; Lindor, Noralane M; Wang, Xianshu; Godwin, Andrew K; Caligo, Maria A; Lombardi, Grazia; Loman, Niklas; Karlsson, Per; Ehrencrona, Hans; Wachenfeldt, Anna von; Barkardottir, Rosa Bjork; Hamann, Ute; Rashid, Muhammad U; Lasa, Adriana; Caldés, Trinidad; Andrés, Raquel; Schmitt, Michael; Assmann, Volker; Stevens, Kristen; Offit, Kenneth; Curado, João; Tilgner, Hagen; Guigó, Roderic; Aiza, Gemma; Brunet, Joan; Castellsagué, Joan; Martrat, Griselda; Urruticoechea, Ander; Blanco, Ignacio; Tihomirova, Laima; Goldgar, David E; Buys, Saundra; John, Esther M; Miron, Alexander; Southey, Melissa; Daly, Mary B; Schmutzler, Rita K; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Deissler, Helmut; Varon-Mateeva, Raymonda; Sutter, Christian; Niederacher, Dieter; Imyamitov, Evgeny; Sinilnikova, Olga M; Stoppa-Lyonne, Dominique; Mazoyer, Sylvie; Verny-Pierre, Carole; Castera, Laurent; de Pauw, Antoine; Bignon, Yves-Jean; Uhrhammer, Nancy; Peyrat, Jean-Philippe; Vennin, Philippe; Fert Ferrer, Sandra; Collonge-Rame, Marie-Agnès; Mortemousque, Isabelle; Spurdle, Amanda B; Beesley, Jonathan; Chen, Xiaoqing; Healey, Sue; Barcellos-Hoff, Mary Helen; Vidal, Marc; Gruber, Stephen B; Lázaro, Conxi; Capellá, Gabriel; McGuffog, Lesley; Nathanson, Katherine L; Antoniou, Antonis C; Chenevix-Trench, Georgia; Fleisch, Markus C; Moreno, Víctor; Pujana, Miguel Angel

    2011-11-01

    Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.

  20. 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.

  1. miR-181b-3p promotes epithelial-mesenchymal transition in breast cancer cells through Snail stabilization by directly targeting YWHAG.

    Science.gov (United States)

    Yoo, Je-Ok; Kwak, Seo-Young; An, Hyun-Ju; Bae, In-Hwa; Park, Myung-Jin; Han, Young-Hoon

    2016-07-01

    Epithelial-mesenchymal transition (EMT) is essential for increased invasion and metastasis during cancer progression. Among the candidate EMT-regulating microRNAs that we previously identified, miR-181b-3p was found to induce EMT in MCF7 breast cancer cells, as indicated by an EMT-characteristic morphological change, increased invasiveness, and altered expression of an EMT marker. Transfection with a miR-181b-3p inhibitor reduced the expression of mesenchymal markers and the migration and invasion of highly invasive breast cancer cells. miR-181b-3p induced the upregulation of Snail, a master EMT inducer and transcriptional repressor of E-cadherin, through protein stabilization. YWHAG was identified as a direct target of miR-181b-3p, downregulation of which induced Snail stabilization and EMT phenotypes. Ectopic expression of YWHAG abrogated the effect of miR-181b-3p, including Snail stabilization and the promotion of invasion. In situ hybridization and immunohistochemical analyses indicated that YWHAG expression was inversely correlated with the expression of miR-181b-3p and Snail in human breast cancer tissues. Furthermore, transfection with miR-181b-3p increased the frequency of metastatic nodule formation in the lungs of mice in experimental metastasis assays using MDA-MB-231 cells. Taken together, our data suggest that miR-181b-3p functions as a metastasis activator by promoting Snail-induced EMT, and may therefore be a therapeutic target in metastatic cancers.

  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. Suberoylanilide hydroxamic acid (SAHA) promotes the epithelial mesenchymal transition of triple negative breast cancer cells via HDAC8/FOXA1 signals.

    Science.gov (United States)

    Wu, Shao; Luo, Zhi; Yu, Peng-Jiu; Xie, Hui; He, Yu-Wen

    2016-01-01

    Inhibitor of histone deacetylases (HDACIs) have great therapeutic value for triple negative breast cancer (TNBC) patients. Interestingly, our present study reveals that suberoyl anilide hydroxamic acid (SAHA), one of the most advanced pan-HDAC inhibitor, can obviously promote in vitro motility of MDA-MB-231 and BT-549 cells via induction of epithelial-mesenchymal transition (EMT). SAHA treatment significantly down-regulates the expression of epithelial markers E-cadherin (E-Cad) while up-regulates the mesenchymal markers N-cadherin (N-Cad), vimentin (Vim) and fibronectin (FN). However, SAHA has no effect on the expression and nuclear translocation of EMT related transcription factors including Snail, Slug, Twist and ZEB. While SAHA treatment down-regulates the protein and mRNA expression of FOXA1 and then decreases its nuclear translocation. Over-expression of FOXA1 markedly attenuates SAHA induced EMT of TNBC cells. Further, silence of HDAC8, while not HDAC6, alleviates the down-regulation of FOXA1 and up-regulation of N-Cad and Vim in MDA-MB-231 cells treated with SAHA. Collectively, our present study reveals that SAHA can promote EMT of TNBC cells via HDAC8/FOXA1 signals, which suggests that more attention should be paid when SAHA is used as anti-cancer agent for cancer treatment.

  4. 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.

  5. Estrogen receptor beta growth-inhibitory effects are repressed through activation of MAPK and PI3K signalling in mammary epithelial and breast cancer cells.

    Science.gov (United States)

    Cotrim, C Z; Fabris, V; Doria, M L; Lindberg, K; Gustafsson, J-Å; Amado, F; Lanari, C; Helguero, L A

    2013-05-09

    Two thirds of breast cancers express estrogen receptors (ER). ER alpha (ERα) mediates breast cancer cell proliferation, and expression of ERα is the standard choice to indicate adjuvant endocrine therapy. ERbeta (ERβ) inhibits growth in vitro; its effects in vivo have been incompletely investigated and its role in breast cancer and potential as alternative target in endocrine therapy needs further study. In this work, mammary epithelial (EpH4 and HC11) and breast cancer (MC4-L2) cells with endogenous ERα and ERβ expression and T47-D human breast cancer cells with recombinant ERβ (T47-DERβ) were used to explore effects exerted in vitro and in vivo by the ERβ agonists 2,3-bis (4-hydroxy-phenyl)-propionitrile (DPN) and 7-bromo-2-(4-hydroxyphenyl)-1,3-benzoxazol-5-ol (WAY). In vivo, ERβ agonists induced mammary gland hyperplasia and MC4-L2 tumour growth to a similar extent as the ERα agonist 4,4',4''-(4-propyl-(1H)-pyrazole-1,3,5-triyl) trisphenol (PPT) or 17β-estradiol (E2) and correlated with higher number of mitotic and lower number of apoptotic features. In vitro, in MC4-L2, EpH4 or HC11 cells incubated under basal conditions, ERβ agonists induced apoptosis measured as upregulation of p53 and apoptosis-inducible factor protein levels and increased caspase 3 activity, whereas PPT and E2 stimulated proliferation. However, when extracellular signal-regulated kinase 1 and 2 (ERK ½) were activated by co-incubation with basement membrane extract or epidermal growth factor, induction of apoptosis by ERβ agonists was repressed and DPN induced proliferation in a similar way as E2 or PPT. In a context of active ERK ½, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/RAC-alpha serine/threonine-protein kinase (AKT) signalling was necessary to allow proliferation stimulated by ER agonists. Inhibition of MEK ½ with UO126 completely restored ERβ growth-inhibitory effects, whereas inhibition of PI3K by LY294002 inhibited ERβ-induced proliferation. These

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

    Directory of Open Access Journals (Sweden)

    Panshi Zhang

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

  7. 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. ...

  8. 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.

  9. Epithelial-Mesenchymal Transition (EMT and Regulation of EMT Factors by Steroid Nuclear Receptors in Breast Cancer: A Review and in Silico Investigation

    Directory of Open Access Journals (Sweden)

    Ioannis A. Voutsadakis

    2016-01-01

    Full Text Available Steroid Nuclear Receptors (SNRs are transcription factors of the nuclear receptor super-family. Estrogen Receptor (ERα is the best-studied and has a seminal role in the clinic both as a prognostic marker but also as a predictor of response to anti-estrogenic therapies. Progesterone Receptor (PR is also used in the clinic but with a more debatable prognostic role and the role of the four other SNRs, ERβ, Androgen Receptor (AR, Glucocorticoid Receptor (GR and Mineralocorticoid Receptor (MR, is starting only to be appreciated. ERα, but also to a certain degree the other SNRs, have been reported to be involved in virtually every cancer-enabling process, both promoting and impeding carcinogenesis. Epithelial-Mesenchymal Transition (EMT and the reverse Mesenchymal Epithelial Transition (MET are such carcinogenesis-enabling processes with important roles in invasion and metastasis initiation but also establishment of tumor in the metastatic site. EMT is governed by several signal transduction pathways culminating in core transcription factors of the process, such as Snail, Slug, ZEB1 and ZEB2, and Twist, among others. This paper will discuss direct regulation of these core transcription factors by SNRs in breast cancer. Interrogation of publicly available databases for binding sites of SNRs on promoters of core EMT factors will also be included in an attempt to fill gaps where other experimental data are not available.

  10. 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 ...

  11. 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

  12. 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

  13. 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 ...

  14. The Polycomb group protein RING1B is overexpressed in ductal breast carcinoma and is required to sustain FAK steady state levels in breast cancer epithelial cells

    Science.gov (United States)

    Bosch, Almudena; Panoutsopoulou, Konstantina; Corominas, Josep Maria; Gimeno, Ramón; Moreno-Bueno, Gema; Martín-Caballero, Juan; Morales, Saleta; Lobato, Tania; Martínez-Romero, Carles; Farias, Eduardo F.; Mayol, Xavier; Cano, Amparo; Hernández-Muáoz, Inmaculada

    2014-01-01

    In early stages of metastasis malignant cells must acquire phenotypic changes to enhance their migratory behavior and their ability to breach the matrix surrounding tumors and blood vessel walls. Epigenetic regulation of gene expression allows the acquisition of these features that, once tumoral cells have escape from the primary tumor, can be reverted. Here we report that the expression of the Polycomb epigenetic repressor Ring1B is enhanced in tumoral cells that invade the stroma in human ductal breast carcinoma and its expression is coincident with that of Fak in these tumors. Ring1B knockdown in breast cancer cell lines revealed that Ring1B is required to sustain Fak expression in basal conditions as well as in Tgfβ-treated cells. Functionally, endogenous Ring1B is required for cell migration and invasion in vitro and for in vivo invasion of the mammary fat pad by tumoral cells. Finally we identify p63 as a target of Ring1B to regulate Fak expression: Ring1B depletion results in enhanced p63 expression, which in turns represses Fak expression. Importantly, Fak downregulation upon Ring1B depletion is dependent on p63 expression. Our findings provide new insights in the biology of the breast carcinoma and open new avenues for breast cancer prognosis and therapy. PMID:24742605

  15. 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.

  16. Phosphoglucose isomerase/autocrine motility factor mediates epithelial-mesenchymal transition regulated by miR-200 in breast cancer cells.

    Science.gov (United States)

    Ahmad, Aamir; Aboukameel, Amro; Kong, Dejuan; Wang, Zhiwei; Sethi, Seema; Chen, Wei; Sarkar, Fazlul H; Raz, Avraham

    2011-05-01

    Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) plays an important role in glycolysis and gluconeogenesis and is associated with invasion and metastasis of cancer cells. We have previously shown its role in the induction of epithelial-mesenchymal transition (EMT) in breast cancer cells, which led to increased aggressiveness; however, the molecular mechanism by which PGI/AMF regulates EMT is not known. Here we show, for the first time, that PGI/AMF overexpression led to an increase in the DNA-binding activity of NF-κB, which, in turn, led to increased expression of ZEB1/ZEB2. The microRNA-200s (miR-200s) miR-200a, miR-200b, and miR-200c are known to negatively regulate the expression of ZEB1/ZEB2, and we found that the expression of miR-200s was lost in PGI/AMF overexpressing MCF-10A cells and in highly invasive MDA-MB-231 cells, which was consistent with increased expression of ZEB1/ZEB2. Moreover, silencing of PGI/AMF expression in MDA-MB-231 cells led to overexpression of miR-200s, which was associated with reversal of EMT phenotype (i.e., mesenchymal-epithelial transition), and these findings were consistent with alterations in the relative expression of epithelial (E-cadherin) and mesenchymal (vimentin, ZEB1, ZEB2) markers and decreased aggressiveness as judged by clonogenic, motility, and invasion assays. Moreover, either reexpression of miR-200 or silencing of PGI/AMF suppressed pulmonary metastases of MDA-MB-231 cells in vivo, and anti-miR-200 treatment in vivo resulted in increased metastases. Collectively, these results suggest a role of miR-200s in PGI/AMF-induced EMT and thus approaches for upregulation of miR-200s could be a novel therapeutic strategy for the treatment of highly invasive breast cancer.

  17. The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Li JP

    2015-02-01

    , but its antitumor effect and underlying mechanisms in the treatment of human breast cancer remain elusive. This study aimed to investigate the effects of Danu on the growth, apoptosis, autophagy, and epithelial-to-mesenchymal transition (EMT and the molecular mechanisms in human breast cancer MCF7 and MDA-MB-231 cells. The results demonstrated that Danu remarkably inhibited cell proliferation, induced apoptosis and autophagy, and suppressed EMT in both breast cancer cell lines. Danu arrested MCF7 and MDA-MB-231 cells in G2/M phase, accompanied by the downregulation of cyclin-dependent kinase 1 and cyclin B1 and upregulation of p21 Waf1/Cip1, p27 Kip1, and p53. Danu significantly decreased the expression of B-cell lymphoma-extra-large (Bcl-xl and B-cell lymphoma 2 (Bcl-2, but increased the expression of Bcl-2-associated X protein (Bax and p53-upregulated modulator of apoptosis (PUMA, and promoted the cleavage of caspases 3 and 9. Furthermore, Danu significantly increased the expression levels of the membrane-bound microtubule-associated protein 1A/1B-light chain 3 (LC3-II and beclin 1 in breast cancer cells, two markers for autophagy. Danu induced the activation of p38 mitogen-activated protein kinase (MAPK and extracellular signal-regulated kinases 1 and 2 (Erk1/2 and inhibited the activation of protein kinase B (Akt/mammalian target of rapamycin (mTOR signaling pathways in breast cancer cells. Treatment with wortmannin (a phosphatidylinositol 3-kinase inhibitor markedly inhibited Danu-induced activation of p38 MAPK and conversion of cytosolic LC3-I to membrane-bound LC3-II. Pharmacological inhibition and small interfering RNA-mediated knockdown of p38 MAPK suppressed Akt activation, resulting in LC3-II accumulation and enhanced autophagy. Pharmacological inhibition and small interfering RNA-mediated knockdown of Erk1/2 also remarkably increased the level of LC3-II in MCF7 cells. Moreover, Danu inhibited EMT in both MCF7 and MDA-MB-231 cells with upregulated E

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. MiR-145 regulates epithelial to mesenchymal transition of breast cancer cells by targeting Oct4.

    Directory of Open Access Journals (Sweden)

    Jiajia Hu

    Full Text Available MiR-145 could regulate tumor growth, apoptosis, migration, and invasion. In our present study, we investigated its role in epithelial-mesenchymal transition (EMT. Expression of miR-145 was decreased in breast tumor tissues at T3&4 stages in comparison with those at T1&2. Over-expression of miR-145 mimics enhanced protein levels of E-cadherin and dampened those of α-SMA and Fibronectin, indicative of its inhibitory role in EMT occurrence. Mechanistic studies showed that miR-145 mimics inhibited Oct4 expression and miR-145 inhibitor enhanced it. Over-expression of Oct4 reversed miR-145-regulated expression of EMT markers, suggesting that Oct4 mediated the inhibitory effects of miR-145. MiR-145 could inhibite the expression of Snail, ZEB1, and ZEB2, while over-expression of Oct4 rescued the effects. Furthermore, Oct-4 induced over-expression of transcription factor Snail, ZEB1 and ZEB2 was mediated by β-catenin. Expression of Slug and Twist were not altered by miR-145/Oct4. Taken together, our results have revealed a novel role of miR-145 on EMT. It inhibits EMT by blocking the expression of Oct4, and downstream transcriptional factors, Snail, ZEB1 and ZEB2.

  2. 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

  3. Quantitative analysis of promoter methylation in exfoliated epithelial cells isolated from breast milk of healthy women.

    Science.gov (United States)

    Wong, Chung M; Anderton, Douglas L; Smith-Schneider, Sallie; Wing, Megan A; Greven, Melissa C; Arcaro, Kathleen F

    2010-10-01

    Promoter methylation analysis of genes frequently silenced in breast cancer is a promising indicator of breast cancer risk, as these methylation events are thought to occur long before presentation of disease. The numerous exfoliated epithelial cells present in breast milk may provide the breast epithelial DNA needed for detailed methylation analysis and assessment of breast cancer risk. Fresh breast milk samples and health, lifestyle, and reproductive history questionnaires were collected from 111 women. Pyrosequencing analysis was conducted on DNA isolated from the exfoliated epithelial cells immunomagnetically separated from the total cell population in the breast milk of 102 women. A total of 65 CpG sites were examined in six tumor suppressor genes: PYCARD (also known as ASC or TMS1), CDH1, GSTP1, RBP1 (also known as CRBP1), SFRP1, and RASSF1. A sufficient quantity of DNA was obtained for meaningful analysis of promoter methylation; women donated an average of 86 ml of milk with a mean yield of 32,700 epithelial cells per ml. Methylation scores were in general low as expected of benign tissue, but analysis of outlier methylation scores revealed a significant relationship between breast cancer risk, as indicated by previous biopsy, and methylation score for several CpG sites in CDH1, GSTP1, SFRP1, and RBP1. Methylation of RASSF1 was positively correlated with women's age irrespective of her reproductive history. Promoter methylation patterns in DNA from breast milk epithelial cells can likely be used to assess breast cancer risk. Additional studies of women at high breast cancer risk are warranted.

  4. 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 ...

  5. 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.

  6. 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.

  7. Metabolic profiling of breast cancer: Differences in central metabolism between subtypes of breast cancer cell lines.

    Science.gov (United States)

    Willmann, Lucas; Schlimpert, Manuel; Halbach, Sebastian; Erbes, Thalia; Stickeler, Elmar; Kammerer, Bernd

    2015-09-01

    Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer.

  8. 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

  9. The cancer genetics and pathology of male breast cancer.

    Science.gov (United States)

    Deb, Siddhartha; Lakhani, Sunil R; Ottini, Laura; Fox, Stephen B

    2016-01-01

    Male breast cancer (MBC) is an uncommon and poorly understood disease. Recent molecular studies have shown important differences from female breast cancer which are likely to influence treatment strategies from the current female-based management towards a more tailored approach. Significantly more MBCs than female breast cancers arise with an underlying germline cancer predisposition, and display a vastly different penetrance compared with females. Furthermore, the genophenotypical association of basal-like cancer with BRCA1 present in female breast cancer is not observed in male breast cancer. Differences in somatic changes between male and female breast cancer have also been reported, with particular enrichment of PIK3CA mutations and a paucity of TP53 mutations. In general, chromosomal-based changes, in particular regions of gains, are seen more frequently in male than female breast cancer and methylation is seen less frequently. Clinically, several molecular subtypes with prognostic relevance have been described, including chromosomal complex high and methylation high groups, and subgroups with profiling signatures pertaining to epithelial mesenchymal transition and hormonal therapy insensitivity. As with female breast cancer, attention to male specific multicentre trials based on the individual characteristics are needed, together with establishment of reliable preclinical models to understand more clearly the pathogenesis of male breast cancer and improve the general poor outcome of this disease.

  10. 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.

  11. Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer

    NARCIS (Netherlands)

    Maxwell, C.A.; Benitez, J.; Gomez-Baldo, L.; Osorio, A.; Bonifaci, N.; Fernandez-Ramires, R.; Costes, S.V.; Guino, E.; Chen, H.; Evans, G.J.; Mohan, P.; Catala, I.; Petit, A.; Aguilar, H.; Villanueva, A.; Aytes, A.; Serra-Musach, J.; Rennert, G.; Lejbkowicz, F.; Peterlongo, P.; Manoukian, S.; Peissel, B.; Ripamonti, C.B.; Bonanni, B.; Viel, A.; Allavena, A.; Bernard, L.; Radice, P.; Friedman, E.; Kaufman, B.; Laitman, Y.; Dubrovsky, M.; Milgrom, R.; Jakubowska, A.; Cybulski, C.; Gorski, B.; Jaworska, K.; Durda, K.; Sukiennicki, G.; Lubinski, J.; Shugart, Y.Y.; Domchek, S.M.; Letrero, R.; Weber, B.L.; Hogervorst, F.B.L.; Rookus, M.A.; Collee, J.M.; Devilee, P.; Ligtenberg, M.J.L.; Luijt, R.B. van der; Aalfs, C.M.; Waisfisz, Q.; Wijnen, J.; Roozendaal, C.E.P. van; Easton, D.F.; Peock, S.; Cook, M.; Oliver, C.; Frost, D.; Harrington, P.; Evans, D.G.; Lalloo, F.; Eeles, R.; Izatt, L.; Chu, C.; Eccles, D.; Douglas, F.; Brewer, C.; Nevanlinna, H.; Heikkinen, T.; Couch, F.J.; Lindor, N.M.; Wang, X.; Godwin, A.K.; Caligo, M.A.; Lombardi, G.; Loman, N.; Karlsson, P.; Ehrencrona, H.; Wachenfeldt, A. von; Bjork Barkardottir, R.; Hamann, U.; Rashid, M.U.; Lasa, A.; Caldes, T.; Andres, R.; Schmitt, M.; Assmann, V.; Stevens, K.; Offit, K.; Curado, J.; Tilgner, H.; Guigo, R.; Aiza, G.; Brunet, J.; Castellsague, J.; Martrat, G.; Urruticoechea, A.; Blanco, I.; Tihomirova, L.

    2011-01-01

    Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest

  12. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer

    NARCIS (Netherlands)

    C.A. Maxwell (Christopher); J. Benitez (Javier); L. Gómez-Baldó (Laia); A. Osorio (Ana); N. Bonifaci (Núria); R. Fernández-Ramires (Ricardo); S.V. Costes (Sylvain); E. Guinó (Elisabet); H. Chen (Helen); G.J.R. Evans (Gareth); P. Mohan (Pooja); I. Català (Isabel); A. Petit (Anna); H. Aguilar (Helena); A. Villanueva (Alberto); A. Aytes (Alvaro); J. Serra-Musach (Jordi); G. Rennert (Gad); F. Lejbkowicz (Flavio); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); C.B. Ripamonti (Carla); B. Bonnani (Bernardo); A. Viel (Alessandra); A. Allavena (Anna); L. Bernard (Loris); P. Radice (Paolo); E. Friedman (Eitan); B. Kaufman (Bella); Y. Laitman (Yael); M. Dubrovsky (Maya); R. Milgrom (Roni); A. Jakubowska (Anna); C. Cybulski (Cezary); B. Górski (Bohdan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); G. Sukiennicki (Grzegorz); J. Lubinski (Jan); Y.Y. Shugart; S.M. Domchek (Susan); R. Letrero (Richard); F.B.L. Hogervorst (Frans); M.A. Rookus (Matti); J.M. Collée (Margriet); P. Devilee (Peter); M.J. Ligtenberg (Marjolijn); R.B. van der Luijt (Rob); C.M. Aalfs (Cora); Q. Waisfisz (Quinten); J.T. Wijnen (Juul); C.E.P. van Roozendaal (Cornelis); D.F. Easton (Douglas); S. Peock (Susan); M. Cook (Margaret); C.T. Oliver (Clare); D. Frost (Debra); P. harrington (Patricia); F. Lalloo (Fiona); R. Eeles (Rosalind); L. Izatt (Louise); C. Chu (Chengbin); D. Eccles (Diana); F. Douglas (Fiona); C. Brewer (Carole); H. Nevanlinna (Heli); T. Heikinen (Tuomas); F.J. Couch (Fergus); N.M. Lindor (Noralane); X. Wang (Xing); A.K. Godwin (Andrew); M.A. Caligo (Maria); G. Lombardi (Grazia); N. Loman (Niklas); P. Karlsson (Per); H. Ehrencrona (Hans); A. von Wachenfeldt (Anna); R.B. Barkardottir (Rosa); U. Hamann (Ute); M.U. Rashid (Muhammad); A. Lasa (Adriana); T. Caldes (Trinidad); R. Andres (Raquel); M. Schmitt (Michael); V. Assmann (Volker); K. Stevens (Kristen); K. Offit (Kenneth); J. Curado (João); H. Tilgner (Hagen); R. Guigó (Roderic); G. Aiza (Gemma); J. Brunet (Joan); J. Castellsagué (Joan); G. Martrat (Griselda); A. Urruticoechea (Ander); I. Blanco (Ignacio); L. Tihomirova (Laima); D. Goldgar (David); S.S. Buys (Saundra); E.M. John (Esther); A. Miron (Alexander); M.C. Southey (Melissa); M.J. Daly (Mark); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); A. Meindl (Alfons); N. Arnold (Norbert); H. Deissler (Helmut); R. Varon-Mateeva (Raymonda); C. Sutter (Christian); D. Niederacher (Dieter); E. Imyamitov (Evgeny); O. Sinilnikova (Olga); D. Stoppa-Lyonne (Dominique); S. Mazoyer (Sylvie); C. Verny-Pierre (Carole); L. Castera (Laurent); A. de Pauw (Antoine); Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); J.-P. Peyrat; P. Vennin (Philippe); S.F. Ferrer; M.-A. Collonge-Rame; I. Mortemousque (Isabelle); A.B. Spurdle (Amanda); J. Beesley (Jonathan); S. Healey (Sue); M.H. Barcellos-Hoff; M. Vidal (Marc); S.B. Gruber (Stephen); C. Lazaro (Conxi); G. Capellá (Gabriel); L. McGuffog (Lesley); K.L. Nathanson (Katherine); A.C. Antoniou (Antonis); G. Chenevix-Trench (Georgia); M.C. Fleisch (Markus); V. Moreno (Víctor); M.A. Pujana; B.L. Weber (Barbara)

    2011-01-01

    textabstractDifferentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like

  13. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer

    NARCIS (Netherlands)

    Maxwell, C.A.; Benítez, J.; Gómez-Baldó, L.; Osorio, A.; Bonifaci, N.; Fernández-Ramires, R.; Costes, S.V.; Guinó, E.; Chen, H.; Evans, G.J.R.; Mohan, P.; Català, I.; Petit, A.; Aguilar, H.; Villanueva, A.; Aytes, A.; Serra-Musach, J.; Rennert, G.; Lejbkowicz, F.; Peterlongo, P.; Manoukian, S.; Peissel, B.; Ripamonti, C.B.; Bonanni, B.; Viel, A.; Allavena, A.; Bernard, L.; Radice, P.; Friedman, E.; Kaufman, B.; Laitman, Y.; Dubrovsky, M.; Milgrom, R.; Jakubowska, A.; Cybulski, C.; Gorski, B.; Jaworska, K.; Durda, K.; Sukiennicki, G.; Lubiński, J.; Shugart, Y.Y.; Domchek, S.M.; Letrero, R.; Weber, B.L.; Hogervorst, F.B.L.; Rookus, M.A.; Collee, J.M.; Devilee, P.; Ligtenberg, M.J.; Luijt, R.B.v.d.; Aalfs, C.M.; Waisfisz, Q.; Wijnen, J.; Roozendaal, C.E.P.v.; Easton, D.F.; Peock, S.; Cook, M.; Oliver, C.; Frost, D.; Harrington, P.; Evans, D.G.; Lalloo, F.; Eeles, R.; Izatt, L.; Chu, C.; Eccles, D.; Douglas, F.; Brewer, C.; Nevanlinna, H.; Heikkinen, T.; Couch, F.J.; Lindor, N.M.; Wang, X.; Godwin, A.K.; Caligo, M.A.; Lombardi, G.; Loman, N.; Karlsson, P.; Ehrencrona, H.; von Wachenfeldt, A.; Barkardottir, R.B.; Hamann, U.; Rashid, M.U.; Lasa, A.; Caldés, T.; Andrés, R.; Schmitt, M.; Assmann, V.; Stevens, K.; Offit, K.; Curado, J.; Tilgner, H.; Guigó, R.; Aiza, G.; Brunet, J.; Castellsagué, J.; Martrat, G.; Urruticoechea, A.; Blanco, I.; Tihomirova, L.; Goldgar, D.E.; Buys, S.; John, E.M.; Miron, A.; Southey, M.; Daly, M.B.; Schmutzler, R.K.; Wappenschmidt, B.; Meindl, A.; Arnold, N.; Deissler, H.; Varon-Mateeva, R.; Sutter, C.; Niederacher, D.; Imyamitov, E.; Sinilnikova, O.M.; Stoppa-Lyonne, D.; Mazoyer, S.; Verny-Pierre, C.; Castera, L.; de Pauw, A.; Bignon, Y.J.; Uhrhammer, N.; Peyrat, J.P.; Vennin, P.; Fert-Ferrer, S.; Collonge-Rame, M.A.; Mortemousque, I.; Spurdle, A.B.; Beesley, J.; Chen, X.; Healey, S.; Barcellos-Hoff, M.H.; Vidal, M.; Gruber, S.B.; Lázaro, C.; Capellá, G.; McGuffog, L.; Nathanson, K.L.; Antoniou, A.C.; Chenevix-Trench, G.; Fleisch, M.C.; Moreno, V.; Pujana, M.A.

    2011-01-01

    Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest

  14. 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: ...

  15. 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.

  16. Expression, regulation and function of epithelial-stromal interaction 1 (breast), EPSTI1

    DEFF Research Database (Denmark)

    Villadsen, René; Lind Nielsen, Helga; Rank, Fritz;

    2008-01-01

    in epithelial cells in close contact with stromal cells. Furthermore, preliminary data indicate that the expression was highest in estrogen receptor negative tumors. By comparison, in normal breast EPSTI1 was expressed primarily in the acini. To address a possible function of the protein we used a human breast...... epithelial cancer cell line, MCF-7, transfected with pRev-Tet-Off and pRevTRE with a FLAG-EPSTI1 insert. When cultured in 3-dimensional assays, the EPSTI1 expressing cells gave rise to more compact structures than the non-expressing cells, which resulted in loosely arranged/hollow structures......The transcript of epithelial-stromal interaction 1 (breast), EPSTI1, was originally found to be upregulated in invasive breast carcinomas as compared to normal breast tissue (Genomics 79:703, 2002). In the present study we investigated the expression, regulation and possible function of the protein...

  17. 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 ...

  18. A 22q11.2 amplification in the region encoding microRNA-650 correlates with the epithelial to mesenchymal transition in breast cancer primary cultures of Mexican patients

    Science.gov (United States)

    Lango-Chavarría, M.; Chimal-Ramírez, G.K.; Ruiz-Tachiquín, M.E.; Espinoza-Sánchez, N.A.; Suárez-Arriaga, M.C.; Fuentes-Pananá, E.M.

    2017-01-01

    Breast cancer ranks first in incidence and mortality in working age women. Cancer initiation and progression relies on accumulation of genetic and epigenetic aberrations that alter cellular processes, among them, epithelial to mesenchymal transition (EMT) denotes particularly aggressive neoplasias given its capacity to invade and metastasize. Several microRNAs (miRNA) have been found able to regulate gene expression at the core of EMT. In this study, the Affymetrix CytoScan HD array was used to analyze three different primary tumor cell isolates from Mexican breast cancer patients. We found an amplification in band 22q11.2 shared by the three samples, in the region that encodes miRNA-650. Overexpression of this miRNA has been associated with downregulation of tumor suppressors ING4 and NDRG2, which have been implicated in cancer progression. Using the Pathway Linker platform the ING4 and NDRG2 interaction networks showed a significant association with signaling pathways commonly deregulated in cancer. Also, several studies support their participation in the EMT. Supporting the latter, we found that the three primary isolates were E-cadherin negative, vimentin positive, presented a cancer stem cell-like phenotype CD44+CD24−/low and were invasive in Transwell invasion assays. This evidence suggests that the gain of region 22q11.2 contributes to trigger EMT. This is the first evidence linking miR-650 and breast cancer. PMID:28101578

  19. 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 ...

  20. Defining the cellular precursors to human breast cancer

    Science.gov (United States)

    Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

    2012-01-01

    Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

  1. Calcium-sensing receptor in breast physiology and cancer

    OpenAIRE

    Wonnam Kim; Wysolmerski, John J.

    2016-01-01

    The calcium-sensing receptor (CaSR) is expressed in normal breast epithelial cells and in breast cancer cells. During lactation, activation of the CaSR in mammary epithelial cells increases calcium transport into milk and inhibits parathyroid hormone-related protein (PTHrP) secretion into milk and into the circulation. The ability to sense changes in extracellular calcium allows the lactating breast to actively participate in the regulation of systemic calcium and bone metabolism, and to coor...

  2. Targeting the Nuclear Cathepsin L CCAAT Displacement Protein/Cut Homeobox Transcription Factor-Epithelial Mesenchymal Transition Pathway in Prostate and Breast Cancer Cells with the Z-FY-CHO Inhibitor.

    Science.gov (United States)

    Burton, Liza J; Dougan, Jodi; Jones, Jasmine; Smith, Bethany N; Randle, Diandra; Henderson, Veronica; Odero-Marah, Valerie A

    2017-03-01

    The epithelial mesenchymal transition (EMT) promotes tumor migration and invasion by downregulating epithelial markers such as E-cadherin and upregulating mesenchymal markers such as vimentin. Cathepsin L (Cat L) is a cysteine protease that can proteolytically activate CCAAT displacement protein/cut homeobox transcription factor (CUX1). We hypothesized that nuclear Cat L may promote EMT via CUX1 and that this could be antagonized with the Cat L-specific inhibitor Z-FY-CHO. Mesenchymal prostate (ARCaP-M and ARCaP-E overexpressing Snail) and breast (MDA-MB-468, MDA-MB-231, and MCF-7 overexpressing Snail) cancer cells expressed lower E-cadherin activity, higher Snail, vimentin, and Cat L activity, and a p110/p90 active CUX1 form, compared to epithelial prostate (ARCaP-E and ARCaP-Neo) and breast (MCF-7 and MCF-7 Neo) cancer cells. There was increased binding of CUX1 to Snail and the E-cadherin promoter in mesenchymal cells compared to epithelial prostate and breast cells. Treatment of mesenchymal cells with the Cat L inhibitor Z-FY-CHO led to nuclear-to-cytoplasmic relocalization of Cat L, decreased binding of CUX1 to Snail and the E-cadherin promoter, reversed EMT, and decreased cell migration/invasion. Overall, our novel data suggest that a positive feedback loop between Snail-nuclear Cat L-CUX1 drives EMT, which can be antagonized by Z-FY-CHO. Therefore, Z-FY-CHO may be an important therapeutic tool to antagonize EMT and cancer progression.

  3. Epigenetic suppression of neprilysin regulates breast cancer invasion

    Science.gov (United States)

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

    2016-01-01

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

  4. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  5. Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hongzhong; Huang, Jing; Yang, Bing; Xiang, Tingxiu; Yin, Xuedong; Peng, Weiyan; Cheng, Wei [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Wan, Jingyuan; Luo, Fuling [Department of Pharmacology, Chongqing Medical University, Chongqing (China); Li, Hongyuan [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rgs726@163.com [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2013-10-01

    Although mangiferin which is a naturally occurring glucosylxanthone has exhibited promising anticancer activities, the detailed molecular mechanism of mangiferin on cancers still remains enigmatic. In this study, the anticancer activity of mangiferin was evaluated in breast cancer cell line-based in vitro and in vivo models. We showed that mangiferin treatment resulted in decreased cell viability and suppression of metastatic potential in breast cancer cells. Further mechanistic investigation revealed that mangiferin induced decreased matrix metalloproteinase (MMP)-7 and -9, and reversal of epithelial–mesenchymal transition (EMT). Moreover, it was demonstrated that mangiferin significantly inhibited the activation of β-catenin pathway. Subsequent experiments showed that inhibiting β-catenin pathway might play a central role in mangiferin-induced anticancer activity through modulation of MMP-7 and -9, and EMT. Consistent with these findings in vitro, the antitumor potential was also verified in mangiferin-treated MDA-MB-231 xenograft mice where significantly decreased tumor volume, weight and proliferation, and increased apoptosis were obtained, with lower expression of MMP-7 and -9, vimentin and active β-catenin, and higher expression of E-cadherin. Taken together, our study suggests that mangiferin might be used as an effective chemopreventive agent against breast cancer. - Highlights: • Mangiferin inhibits growth and metastatic potential in breast cancer cells. • Mangiferin down-regulates MMP-7 and -9 in breast cancer cells. • Mangiferin induces the reversal of EMT in metastatic breast cancer cells. • Mangiferin inhibits the activation of β-catenin pathway in breast cancer cells. • Inhibiting β-catenin is responsible for the antitumor activity of mangiferin.

  6. N1-Guanyl-1,7-Diaminoheptane Sensitizes Estrogen Receptor Negative Breast Cancer Cells to Doxorubicin by Preventing Epithelial-Mesenchymal Transition through Inhibition of Eukaryotic Translation Initiation Factor 5A2 Activation

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2015-08-01

    Full Text Available Background: Approximately 30% of breast cancer does not express the estrogen receptor (ER, which is necessary for endocrine-based therapy approaches. Many studies demonstrated that eukaryotic translation initiation factor 5A2 (eIF5A2 serves as a proliferation-related oncogene in tumorigenic processes. Methods: The present study used cell viability assays, EdU incorporation assays, western blot, and immunofluorescence to explore whether N1-guanyl-1,7-diaminoheptane (GC7, which inhibits eIF5A2 activation, exerts synergistic cytotoxicity with doxorubicin in breast cancer. Results: We found that GC7 enhanced doxorubicin cytotoxicity in ER-negative HCC1937 cells but had little effect in ER-positive MCF-7 and Bcap-37 cells. Administration of GC7 reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT in ER-negative breast cancer cells. Knockdown of eIF5A2 by siRNA inhibited the doxorubicin-induced EMT in ER-negative HCC1937 cells. Conclusion: These data demonstrated that GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in estrogen negative breast cancer cells by preventing EMT through inhibition of eIF5A2 activation.

  7. Diagnosing Breast Cancer Using Protease Fingerprint

    Science.gov (United States)

    2002-06-01

    substrates for MMP-l4 (NTl- MNP ) . In addition, a different proteomic approach of achieving the original aim of identifying new diagnostic marker for...disease-relevant enzymes , serine hydrolases, in normal epithelial cells and several breast cancer cells. A novel potential tumor suppressor protein

  8. 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

  9. MicroRNA-200c: A Novel Way to Attack Breast Cancer Metastases by Restoring the Epithelial Phenotype

    Science.gov (United States)

    2012-12-01

    percentage of stem cell-like cells) compared to adjacent uninvolved epithelium . Figure 5. In situ hybridization for miR-222 and immunohistochemistry for...expressed in epithelium and inhibits genes that should not be expressed in normal epithelial cells. Although in this proposal we use lentiviral delivery of...Ishikawa H and Hec50co cells. Gynecol Oncol 2007;106:52–64. 20. Kyo S, Nakamura M, Kiyono T, et al. Successful immortalization of endometrial glandular

  10. 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 ...

  11. 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.

  12. 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

  13. HER2 induces expression of leptin in human breast epithelial cells

    Directory of Open Access Journals (Sweden)

    Aree Moon

    2012-12-01

    Full Text Available A close association between the obesity hormone leptin andbreast cancer progression has been suggested. The presentstudy investigated the molecular mechanism for enhancedleptin expression in breast cancer cells and its functionalsignificance in breast cancer aggressiveness. We examinedwhether leptin expression level is affected by the oncoproteinhuman epidermal growth factor receptor2 (HER2, which isoverexpressed in ∼30% of breast tumors. Here, we report, forthe first time, that HER2 induces transcriptional activation ofleptin in MCF10A human breast epithelial cells. We alsoshowed that p38 mitogen-activated protein kinase signalingwas involved in leptin expression induced by HER2. Weshowed a crucial role of leptin in the invasiveness ofHER2-MCF10A cells using an siRNA molecule targeting leptin.Taken together, the results indicate a molecular link betweenHER2 and leptin, providing supporting evidence that leptinrepresents a target for breast cancer therapy.

  14. Na+/H+ exchanger NHE1 regulation modulates metastatic potential and epithelial-mesenchymal transition of triple-negative breast cancer cells.

    Science.gov (United States)

    Amith, Schammim Ray; Wilkinson, Jodi Marie; Fliegel, Larry

    2016-04-19

    In triple-negative breast cancer (TNBC), the high recurrence rate, increased invasion and aggressive metastatic formation dictate patient survival. We previously demonstrated a critical role for the Na+/H+ exchanger isoform 1 (NHE1) in controlling metastasis of triple-negative cells. Here, we investigated the effect of changes to three regulatory loci of NHE1. Two via the Ras/Raf/ERK/p90RSK pathway: p90RSK/14-3-3 (S703A) and ERK1/2 (S766,770,771A, SSSA) and a third via a calmodulin-binding domain (K641,R643,645,647E, 1K3R4E). MDA-MB-231 cells with a mutation at the p90RSK site (S703A-NHE1) changed from a wild-type mesenchymal morphology to a smaller epithelial-like phenotype with a loss of expression of mesenchymal marker vimentin. S703A cells also had reduced metastatic potential and markedly decreased rates of migration, invasion, spheroid growth, anchorage-dependent and soft agar colony formation. Similarly, BI-D1870, a specific inhibitor of p90RSK, significantly inhibited the metastatic potential of highly invasive MDA-MB-231 and moderately invasive MDA-MB-468 TNBC cells, but was minimally effective in non-invasive Hs578T TNBC cells. In contrast, invasion and spheroid growth were unaffected in cells containing NHE1 with mutations interfering with its activation by ERK1/2 (SSSA), though rates of migration and colony formation were reduced. Cells with a constitutive activation of NHE1 via the 1K3R4E mutation exhibited higher rates of migration, invasion, and spheroid growth. Taken together, our data demonstrate the critical role of NHE1 in metastasis, and suggest a novel link between NHE1 and the expression and cytosolic organization of vimentin, a key factor in epithelial-mesenchymal transition, that is dependent on p90RSK/14-3-3-mediated activation of the exchanger.

  15. 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.

  16. 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.

  17. 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...

  18. 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 ...

  19. 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 ...

  20. 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.

  1. Androgens and breast cancer in men and women.

    Science.gov (United States)

    Dimitrakakis, Constantine

    2011-09-01

    Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Clinical and nonhuman primate studies support the notion that androgens inhibit mammary proliferation and, thus, may protect from breast cancer. On the other hand, administration of conventional estrogen treatment suppresses endogenous androgens and may, thus, enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk, but the impact of this combined use on mammary gland homeostasis still needs evaluation.

  2. Down-Regulation of miR-92 in Breast Epithelial Cells and in Normal but Not Tumour Fibroblasts Contributes to Breast Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Laura Smith

    Full Text Available MicroRNA (miR expression is commonly dysregulated in many cancers, including breast. MiR-92 is one of six miRs encoded by the miR-17-92 cluster, one of the best-characterised oncogenic miR clusters. We examined expression of miR-92 in the breast epithelium and stroma during breast cancer progression. We also investigated the role of miR-92 in fibroblasts in vitro and showed that down-regulation in normal fibroblasts enhances the invasion of breast cancer epithelial cells.We used laser microdissection (LMD to isolate epithelial cells from matched normal, DCIS and invasive tissue from 9 breast cancer patients and analysed miR-92 expression by qRT-PCR. Expression of ERβ1, a direct miR-92 target, was concurrently analysed for each case by immunohistochemistry. LMD was also used to isolate matched normal (NFs and cancer-associated fibroblasts (CAFs from 14 further cases. Effects of miR-92 inhibition in fibroblasts on epithelial cell invasion in vitro was examined using a Matrigel™ assay. miR-92 levels decreased in microdissected epithelial cells during breast cancer progression with highest levels in normal breast epithelium, decreasing in DCIS (p<0.01 and being lowest in invasive breast tissue (p<0.01. This was accompanied by a shift in cell localisation of ERβ1 from nuclear expression in normal breast epithelium to increased cytoplasmic expression during progression to DCIS (p = 0.0078 and invasive breast cancer (p = 0.031. ERβ1 immunoreactivity was also seen in stromal fibroblasts in tissues. Where miR-92 expression was low in microdissected NFs this increased in matched CAFs; a trend also seen in cultured primary fibroblasts. Down-regulation of miR-92 levels in NFs but not CAFs enhanced invasion of both MCF-7 and MDA-MB-231 breast cancer epithelial cells.miR-92 is gradually lost in breast epithelial cells during cancer progression correlating with a shift in ERβ1 immunoreactivity from nuclei to the cytoplasm. Our data support a functional

  3. EFA6B antagonizes breast cancer.

    Science.gov (United States)

    Zangari, Joséphine; Partisani, Mariagrazia; Bertucci, François; Milanini, Julie; Bidaut, Ghislain; Berruyer-Pouyet, Carole; Finetti, Pascal; Long, Elodie; Brau, Frédéric; Cabaud, Olivier; Chetaille, Bruno; Birnbaum, Daniel; Lopez, Marc; Hofman, Paul; Franco, Michel; Luton, Frédéric

    2014-10-01

    One of the earliest events in epithelial carcinogenesis is the dissolution of tight junctions and cell polarity signals that are essential for normal epithelial barrier function. Here, we report that EFA6B, a guanine nucleotide exchange factor for the Ras superfamily protein Arf6 that helps assemble and stabilize tight junction, is required to maintain apico-basal cell polarity and mesenchymal phenotypes in mammary epithelial cells. In organotypic three-dimensional cell cultures, endogenous levels of EFA6B were critical to determine epithelial-mesenchymal status. EFA6B downregulation correlated with a mesenchymal phenotype and ectopic expression of EFA6B hampered TGFβ-induced epithelial-to-mesenchymal transition (EMT). Transcriptomic and immunohistochemical analyses of human breast tumors revealed that the reduced expression of EFA6B was associated with loss of tight junction components and with increased signatures of EMT, cancer stemness, and poor prognosis. Accordingly, tumors with low levels of EFA6B were enriched in the aggressive triple-negative and claudin-low breast cancer subtypes. Our results identify EFA6B as a novel antagonist in breast cancer and they point to its regulatory and signaling pathways as rational therapeutic targets in aggressive forms of this disease.

  4. 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...

  5. A MYC-Driven Change in Mitochondrial Dynamics Limits YAP/TAZ Function in Mammary Epithelial Cells and Breast Cancer.

    Science.gov (United States)

    von Eyss, Björn; Jaenicke, Laura A; Kortlever, Roderik M; Royla, Nadine; Wiese, Katrin E; Letschert, Sebastian; McDuffus, Leigh-Anne; Sauer, Markus; Rosenwald, Andreas; Evan, Gerard I; Kempa, Stefan; Eilers, Martin

    2015-12-14

    In several developmental lineages, an increase in MYC expression drives the transition from quiescent stem cells to transit-amplifying cells. We show that MYC activates a stereotypic transcriptional program of genes involved in cell growth in mammary epithelial cells. This change in gene expression indirectly inhibits the YAP/TAZ co-activators, which maintain the clonogenic potential of these cells. We identify a phospholipase of the mitochondrial outer membrane, PLD6, as the mediator of MYC activity. MYC-dependent growth strains cellular energy resources and stimulates AMP-activated kinase (AMPK). PLD6 alters mitochondrial fusion and fission dynamics downstream of MYC. This change activates AMPK, which in turn inhibits YAP/TAZ. Mouse models and human pathological data show that MYC enhances AMPK and suppresses YAP/TAZ activity in mammary tumors.

  6. 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

  7. 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 ...

  8. 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 ...

  9. 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

  10. 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 ...

  11. Induction of PTEN-p53 crosstalk in mammary epithelial cells: A novel mechanism of breast cancer prevention by the dietary factor genistein

    Science.gov (United States)

    Consumption of soy foods either at an early age or for lifetime has been associated with reduced risk for developing breast cancer in humans and in animal models. However, this association continues to be controversial, and the precise mechanisms for protection remain elusive. Among the soy products...

  12. Three interrelated themes in current breast cancer research: gene addiction, phenotypic plasticity, and cancer stem cells.

    Science.gov (United States)

    Cardiff, Robert D; Couto, Suzana; Bolon, Brad

    2011-10-25

    Recent efforts to understand breast cancer biology involve three interrelated themes that are founded on a combination of clinical and experimental observations. The central concept is gene addiction. The clinical dilemma is the escape from gene addiction, which is mediated, in part, by phenotypic plasticity as exemplified by epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition. Finally, cancer stem cells are now recognized as the basis for minimal residual disease and malignant progression over time. These themes cooperate in breast cancer, as induction of epithelial-to-mesenchymal transition enhances self-renewal and expression of cancer stem cells, which are believed to facilitate tumor resistance.

  13. GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast.

    Science.gov (United States)

    Scaling, Allison L; Prossnitz, Eric R; Hathaway, Helen J

    2014-06-01

    17β-Estradiol (estrogen), through receptor binding and activation, is required for mammary gland development. Estrogen stimulates epithelial proliferation in the mammary gland, promoting ductal elongation and morphogenesis. In addition to a developmental role, estrogen promotes proliferation in tumorigenic settings, particularly breast cancer. The proliferative effects of estrogen in the normal breast and breast tumors are attributed to estrogen receptor α. Although in vitro studies have demonstrated that the G protein-coupled estrogen receptor (GPER, previously called GPR30) can modulate proliferation in breast cancer cells both positively and negatively depending on cellular context, its role in proliferation in the intact normal or malignant breast remains unclear. Estrogen-induced GPER-dependent proliferation was assessed in the immortalized nontumorigenic human breast epithelial cell line, MCF10A, and an ex vivo organ culture model employing human breast tissue from reduction mammoplasty or tumor resections. Stimulation by estrogen and the GPER-selective agonist G-1 increased the mitotic index in MCF10A cells and proportion of cells in the cell cycle in human breast and breast cancer explants, suggesting increased proliferation. Inhibition of candidate signaling pathways that may link GPER activation to proliferation revealed a dependence on Src, epidermal growth factor receptor transactivation by heparin-bound EGF and subsequent ERK phosphorylation. Proliferation was not dependent on matrix metalloproteinase cleavage of membrane-bound pro-HB-EGF. The contribution of GPER to estrogen-induced proliferation in MCF10A cells and breast tissue was confirmed by the ability of GPER-selective antagonist G36 to abrogate estrogen- and G-1-induced proliferation, and the ability of siRNA knockdown of GPER to reduce estrogen- and G-1-induced proliferation in MCF10A cells. This is the first study to demonstrate GPER-dependent proliferation in primary normal and malignant

  14. Subcellular localization of YKL-40 in normal and malignant epithelial cells of the breast

    DEFF Research Database (Denmark)

    Roslind, A.; Balslev, E.; Kruse, H.

    2008-01-01

    . YKL-40 protein expression was redistributed in carcinoma versus normal glandular tissue of the breast. A reduced expression of YKL-40 in relation to intermediate filaments and desmosomes was found in tumor cells. Changes in YKL-40 expression suggest that the function of YKL-40 in cells of epithelial......YKL-40 is a new prognostic biomarker in cancer. The biological function is only poorly understood. This study aimed at determining the subcellular localization of YKL-40, using immunogold labeling, in normal epithelial cells and in malignant tumor cells of the breast by immunoelectron microscopy...

  15. Strategy against micrometastasis of epithelial cancer: Detection and elimination

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Tumor metastasis is generally agreed to be the major cause of cancer death. Over the last few years, studies of new diagnosis techniques and tumor immunotherapy have made great progress. Recent clinical studies on the occult metastases of breast, lung and colorectal cancer all suggested that the detection of micrometastases in bone marrow is prognostically important and provides substantial evidence of tumor dissemination. On the other hand, two kinds of the mAb-based immunotherapy have been approved for the treatment against epithelial cancer. Monoclonal antibody (mAb) 17-1A for colorectal carcinomas and mAb herceptin for breast cancer both have produced good curative effects. Potential therapeutics based on some antibodies with prominent antitumor activity also has shown obvious clinical effect. These studies indicate that detection of micrometastasis in circulatory system and immunotherapy by eliminating metastatic malignant cells suggested a new strategy against the metastatic cancer.

  16. 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.

  17. The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn; Villadsen, Ren& #233; ; Ronnov-Jessen, Lone; Bissell, Mina J.

    2001-05-12

    The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neoplastic breast epithelial cells may be substantially more plastic in their differentiation repertoire than previously anticipated. Thus, along with an increasing availability of markers for the myoepithelial lineage, at least a partial differentiation towards this lineage is being revealed frequently. It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may indeed have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells, epithelial to mesenchymal transition-derived cells, genuine stromal cells and myofibroblasts share common markers, we now need to define a more ambitious set of markers to distinguish these cell types in the microenvironment of the tumors. This is necessary because the different microenvironments may confer different clinical outcomes. The aim of this commentary is to describe some of the inherent complexities in defining cellular phenotypes in the microenvironment of breast cancer and to expand wherever possible on the implications for tumor suppression and progression.

  18. 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

  19. Role of ornithine decarboxylase in breast cancer

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  20. 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...

  1. 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.

  2. Panepoxydone targets NF-kB and FOXM1 to inhibit proliferation, induce apoptosis and reverse epithelial to mesenchymal transition in breast cancer.

    Directory of Open Access Journals (Sweden)

    Ritu Arora

    Full Text Available BACKGROUND: Triple-negative breast cancer (TNBC is a highly diverse group that is associated with an aggressive phenotype. Its treatment has been challenging due to its heterogeneity and absence of well-defined molecular targets. Thus, there is an urgent need to identify novel agents with therapeutic application. NF-κB is over-expressed in many breast cancers; thus, inactivation of the NF-κB pathway could serve as a therapeutic target. Here we report for the first time the anti-tumor activity of panepoxydone (PP, a NF-κB inhibitor isolated from an edible mushroom, in several breast cancer cell lines. METHODS: We investigated the effects of PP on cell growth, migration-invasion, apoptosis and EMT-related proteins expression in MCF-7 and TNBC cell lines MDA-MB-231, MDA-MB-468 and MDA-MB-453. RESULTS: Significant antitumor activity was seen in all cell lines, with differential responses noted in cell-line specific manner. Treatment with PP resulted in significant cytotoxicity, decreased invasion, migration and increased apoptosis in all cell lines tested. Up-regulation of Bax and cleaved PARP and down-regulation of Bcl-2, survivin, cyclin D1 and caspase 3 were noted in PP-treated breast cancer cells. The antitumor effect of PP appeared related to its ability to inhibit the phosphorylation of inhibitor of NF-κB (IκBα with cytoplasmic accumulation. PP treatment also down-regulated FOXM1 which resulted in a reversal of EMT. Similar results were obtained after silencing of NF-kB and FOXM1. CONCLUSION: Altogether, these studies show, for the first time the antitumor activity of PP against breast cancer cells, in particular TNBC cells. Furthermore, it highlights the concept that optimal treatment of TNBC warrants attention to the differential sensitivity of various TNBC subtypes to therapeutic agents. These results suggest that the PP may be a potentially effective chemopreventive or therapeutic agent against breast cancer. However, additional

  3. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis.

    Science.gov (United States)

    Visvader, Jane E

    2009-11-15

    The epithelium of the mammary gland exists in a highly dynamic state, undergoing dramatic morphogenetic changes during puberty, pregnancy, lactation, and regression. The recent identification of stem and progenitor populations in mouse and human mammary tissue has provided evidence that the mammary epithelium is organized in a hierarchical manner. Characterization of these normal epithelial subtypes is an important step toward understanding which cells are predisposed to oncogenesis. This review summarizes progress in the field toward defining constituent cells and key molecular regulators of the mammary epithelial hierarchy. Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity.

  4. 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 ...

  5. Pregnancy and its role in breast cancer

    Directory of Open Access Journals (Sweden)

    Filipe Correia Martins

    2011-12-01

    Full Text Available Early full-term pregnancy is the only recognized factor able to prevent breast cancer. There are several hypotheses to explain the mechanisms of this protection, namely an altered hormonal milieu, a differentiation process or a switch in stem cell properties. To explore them, authors have been using animal models, mainly in rodents. Hormonal administration with estrogen and progesterone was the most widely used process to mimic the mammary changes during pregnancy. We have recently proposed that this enigmatic protective role of a full-term birth in breast cancer is carried out by tumor inhibition mediated by differentiated mammary epithelial cells. This explanation may give a new perspective of breast cancer prevention and treatment.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. Diet, Stem Cells, and Breast Cancer Prevention

    Science.gov (United States)

    2011-01-01

    comprised of fibroblasts, endothelial cells and adipocytes, which collectively form the mammary fat pad . Breast cancer originates from subversions of...luminal epithelial cells embedded in a complex stromal matrix (‘mammary fat pad ’) comprised predominantly of fibroblasts, adipocytes and macrophages (Fig. 1...report, we showed that limited exposure (i.e., in utero and lactational only) of female rat offspring to a maternal diet containing soy protein isolate

  12. 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

  13. 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 ...

  14. 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.

  15. Phthalates stimulate the epithelial to mesenchymal transition through an HDAC6-dependent mechanism in human breast epithelial stem cells.

    Science.gov (United States)

    Hsieh, Tsung-Hua; Tsai, Cheng-Fang; Hsu, Chia-Yi; Kuo, Po-Lin; Lee, Jau-Nan; Chai, Chee-Yin; Hou, Ming-Feng; Chang, Chia-Cheng; Long, Cheng-Yu; Ko, Ying-Chin; Tsai, Eing-Mei

    2012-08-01

    Phthalates are environmental hormone-like molecules that are associated with breast cancer risk and are involved in metastasis, a process that requires the epithelial-mesenchymal transition (EMT). However, few studies have addressed the potential effects of phthalates on stem cells. Here we tested the hypothesis that phthalates such as butyl benzyl phthalate and di-n-butyl phthalate induce EMT in R2d cells, a stem cell-derived human breast epithelial cell line that is responsive to estradiol for tumor development. We observed that phthalates induced EMT as evidenced by morphological changes concomitant with increased expression of mesenchymal markers and decreased expression of epithelial markers. Molecular mechanism studies revealed that histone deacetylase 6 (HDAC6) is required for phthalate-induced cell migration and invasion during EMT in vitro and metastasis into the lungs of nude mice. We also constructed a series of mutant HDAC6 promoter fragments and found that the transcription factor AP-2a plays a novel role in regulating the HDAC6 promoter. Furthermore, phthalates stimulated estrogen receptors and triggered the downstream EGFR-PKA signaling cascade, leading to increased expression of AP-2a in the nucleus. We also observed that phthalates increased expression of the PP1/HDAC6 complex and caused Akt activation and GSK3β inactivation, leading to transcriptional activation of vimentin through the β-catenin-TCF-4/LEF1 pathway. Understanding the signaling cascades of phthalates that activate EMT through HDAC6 in breast epithelial stem cells provides the identification of novel therapeutic target for human breast cancer.

  16. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    Science.gov (United States)

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  17. 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

  18. 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

  19. The oncogenic potential of human cytomegalovirus and breast cancer.

    Directory of Open Access Journals (Sweden)

    Georges eHerbein

    2014-08-01

    Full Text Available Breast cancer is among the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses and therapeutic possibilities. The human cytomegalovirus (HCMV is a multifaceted highly host specific betaherpesvirus that is regarded as asymptomatic or mildly pathogenic virus in immunocompetent host. HCMV may cause serious in utero infections as well as acute and chronic complications in immunocompromised individual. The involvement of HCMV in late inflammatory complications underscores its possible role in inflammatory diseases and cancer. HCMV targets a variety of cell types in vivo, including macrophages, epithelial cells, endothelial cells, fibroblasts, stromal cells, neuronal cells, smooth muscle cells, and hepatocytes. HCMV can be detected in the milk after delivery and thereby HCMV could spread to adjacent mammary epithelial cells. HCMV also infects macrophages and induces an atypical M1/M2 phenotype, close to the tumor associated macrophage phenotype, which is associated with the release of cytokines involved in cancer initiation or promotion and breast cancer of poor prognosis. HCMV antigens and DNA have been detected in tissue biopsies of breast cancers and elevation in serum HCMV IgG antibody levels has been reported to precede the development of breast cancer in some women. In this review, we will discuss the potential role of HCMV in the initiation and progression of breast cancer.

  20. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    1997-07-01

    mammary epithelial cells ( Stampfer , 1985). Protein from 184 cell lysate was kindly supplied by Dr. Bruce Lessey, University of North Carolina, Chapel...characterization of a spontaneously immortalized human breast epithelial cell line, MCF- 10. Cancer Res. 50, 6075-6086. Stampfer , M.R. (1985). Isolation and...Exp Cell Neri, Satya Murthy, Christopher Stackpole and Res, 204, 171-80. Janet Price who provided unpublished data, 15. Liotta LA, 1992, Cancer cell

  1. 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...

  2. Down-regulation of CEACAM1 in breast cancer.

    Science.gov (United States)

    Yang, Changcheng; He, Pingqing; Liu, Yiwen; He, Yiqing; Yang, Cuixia; Du, Yan; Zhou, Muqing; Wang, Wenjuan; Zhang, Guoliang; Wu, Man; Gao, Feng

    2015-10-01

    Carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1) is a type 1 transmembrane glycoprotein belonging to the CEA family, which has been found to exist as either soluble forms in body fluids or membrane-bound forms on the cell surface. Aberrant CEACAM1 expression is associated with tumor progression and has been found in a variety of human malignancies. Increasing interest has been devoted to the expression of CEACAM1 in breast cancer, but most of these findings are contradictory. The aim of this study was to investigate CEACAM1 expression in breast cancer in greater detail. Using immunohistochemical staining, we found that CEACAM1 expression was reduced or lost in breast cancer tissues compared with noncancerous breast tissues. In addition, soluble CEACAM1 levels in the culture medium of breast cancer cell lines were significantly lower than those in a nontumorigenic breast epithelial cell line. Immunofluorescence analysis consistently showed that breast cancer cell lines have relatively low expression of membrane-bound CEACAM1. Furthermore, CEACAM1 mRNA and protein expression levels were down-regulated in breast cancer cell lines as measured using real-time reverse transcriptase-polymerase chain reaction and western blot analysis, respectively. Taken together, our results demonstrate a systematic down-regulation of CEACAM1 in breast cancer and suggest that a strategy to restore CEACAM1 expression may be helpful for the treatment of breast cancer.

  3. [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.

  4. 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 ...

  5. 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)

  6. 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 ...

  7. 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.

  8. Getting free of breast cancer

    DEFF Research Database (Denmark)

    Halttunen, Arja; Hietanen, P; Jallinoja, P

    1992-01-01

    Twenty-two breast cancer patients who were relapse-free and had no need for cancer-related treatment were interviewed 8 years after mastectomy in order to evaluate their feelings of getting free of breast cancer and the meaning of breast cancer in their lives. The study is a part of an intervention...... and follow-up study of 57 breast cancer patients. Half of the 22 patients still had frequent or occasional thoughts of recurrence and over two-thirds still thought they had not been 'cured' of cancer. More than half of the patients admitted that going through breast cancer had made them more mature. Women...... 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...

  9. 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

  10. 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

  11. 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.

  12. Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

    Science.gov (United States)

    2016-05-02

    Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell

  13. 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.

  14. 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.

  15. 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.

  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. Calcium-sensing receptor in breast physiology and cancer

    Directory of Open Access Journals (Sweden)

    Wonnam Kim

    2016-09-01

    Full Text Available The calcium-sensing receptor (CaSR is expressed in normal breast epithelial cells and in breast cancer cells. During lactation, activation of the CaSR in mammary epithelial cells increases calcium transport into milk and inhibits parathyroid hormone-related protein (PTHrP secretion into milk and into the circulation. The ability to sense changes in extracellular calcium allows the lactating breast to actively participate in the regulation of systemic calcium and bone metabolism, and to coordinate calcium usage with calcium availability during milk production. Interestingly, as compared to normal breast cells, in breast cancer cells, the regulation of PTHrP secretion by the CaSR becomes rewired due to a switch in its G-protein usage such that activation of the CaSR increases instead of decreases PTHrP production. In normal cells the CaSR couples to Gi to inhibit cAMP and PTHrP production, whereas in breast cancer cells, it couples to Gs to stimulate cAMP and PTHrP production. Activation of the CaSR on breast cancer cells regulates breast cancer cell proliferation, death and migration, in part, by stimulating PTHrP production. In this article, we discuss the biology of the CaSR in the normal breast and in breast cancer, and review recent findings suggesting that the CaSR activates a nuclear pathway of PTHrP action that stimulates cellular proliferation and inhibits cell death, helping cancer cells adapt to elevated extracellular calcium levels. Understanding the diverse actions mediated by the CaSR may help us better understand lactation physiology, breast cancer progression and osteolytic bone metastases.

  18. Parity-Induced Protection Against Breast Cancer

    Science.gov (United States)

    2000-07-01

    mammary gland included markers for mammary epithelial differentiation, such as the milk protein genes, a-casein, f3-casein, y-casein, K-casein, whey ...Accession Number Function Avg. Fold Change Northern Gamma-Casein D10215 Milk 20 Y Whey Acidic Protein J00544 Milk 23.7 Y Alpha-Casein M36780 Milk 4.2...Journal of the National Cancer Institute 68, 211-7. 44 Proprietary Data Lund, E. (1991). Breast cancer mortality and the change in fertility risk

  19. Exometabolom analysis of breast cancer cell lines: Metabolic signature.

    Science.gov (United States)

    Willmann, Lucas; Erbes, Thalia; Halbach, Sebastian; Brummer, Tilman; Jäger, Markus; Hirschfeld, Marc; Fehm, Tanja; Neubauer, Hans; Stickeler, Elmar; Kammerer, Bernd

    2015-08-21

    Cancer cells show characteristic effects on cellular turnover and DNA/RNA modifications leading to elevated levels of excreted modified nucleosides. We investigated the molecular signature of different subtypes of breast cancer cell lines and the breast epithelial cell line MCF-10A. Prepurification of cell culture supernatants was performed by cis-diol specific affinity chromatography using boronate-derivatized polyacrylamide gel. Samples were analyzed by application of reversed phase chromatography coupled to a triple quadrupole mass spectrometer. Collectively, we determined 23 compounds from RNA metabolism, two from purine metabolism, five from polyamine/methionine cycle, one from histidine metabolism and two from nicotinate and nicotinamide metabolism. We observed major differences of metabolite excretion pattern between the breast cancer cell lines and MCF-10A, just as well as between the different breast cancer cell lines themselves. Differences in metabolite excretion resulting from cancerous metabolism can be integrated into altered processes on the cellular level. Modified nucleosides have great potential as biomarkers in due consideration of the heterogeneity of breast cancer that is reflected by the different molecular subtypes of breast cancer. Our data suggests that the metabolic signature of breast cancer cell lines might be a more subtype-specific tool to predict breast cancer, rather than a universal approach.

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

    Science.gov (United States)

    2005-07-01

    Madam , The project entitled INCREASING BREAST CANCER SURVEILLANCE AMONG AFRICAN AMERICAN BREAST CANCER SURVIVORS includes activities involving human...B b- d § fr. Thomisonwill Work e .y .With’Dra) Vdldf naTir, W and y Bo • rganif Janidorf on data a"_`l- ssi reatihfiutfor pres~entatidns and publi

  1. Digital image analysis of breast epithelial cells collected by random periareolar fine-needle aspirates (RPFNA) from women at high risk for breast cancer taking hormone replacement and the aromatase inhibitor, letrozole, for six months.

    Science.gov (United States)

    Frank, Denise H; Kimler, Bruce F; Fabian, Carol J; Ranger-Moore, James; Yozwiak, Michael; Bartels, Hubert G; Alberts, David S; Bartels, Peter H

    2009-06-01

    Aromatase inhibitors are currently being evaluated as preventive agents in post-menopausal women at high risk for breast cancer. A phase II trial of 42 women on hormone replacement therapy (HRT) treated with letrozole for 6 months showed Ki-67 was reduced by 66% but showed no change in cytomorphology or Masood score. Subsequent image analytical procedures (karyometry) conducted on a subset of the samples captured subvisual information that showed reduced cellular abnormality after 6 months of letrozole. In the present study we expanded on the preliminary karyometry study to determine if the change in karyometric measurements corresponded to changes in risk biomarkers quantified in the Phase II trial; and secondly, whether these biomarkers might be used together to serve as markers of response in individual cases. Pap stained slides from the Phase II trial were used. Epithelial cell images were digitized on a CCD video-microphotometer and the nuclei were segmented from the field using a semiautomatic algorithm. Nine out of 37 cases analyzed showed a numerical decrease in all three markers, although only three of these exhibited changes substantial enough to be considered as an improvement. However, 12 cases showed improvement by cytology (a decrease in Masood score of at least 2), an additional 13 cases demonstrated a reduction in Ki-67 expression by 50% of the median baseline value, and an additional five cases exhibited a decrease of at least 10% in abnormal cells by nuclear morphometry. Thus, a total of 30 of 37 cases (81%) showed improvement in at least one marker. There was no correlation between changes in Ki-67%, karyometric abnormality, and Masood score change other than specimens that exhibited an improvement in cytology also displayed greater decreases in nuclear morphometry abnormalities. Given the heterogeneity of mechanisms leading to malignancy, the quantitative analysis of nuclear chromatin patterns may be valuable as a global, or integrating

  2. Neoplastic transformation of breast epithelial cells by genotoxic stress

    OpenAIRE

    Raman Venu; Winnard Paul T; Botlagunta Mahendran

    2010-01-01

    Abstract Background Exposure to genotoxic stresses such as radiation and tobacco smoke can cause increased cancer incidence rate as reflected in an in depth meta-analysis of data for women and breast cancer incidence. Published reports have indicated that exposures to low dose radiation and tobacco smoke are factors that contribute to the development of breast cancer. However, there is a scarcity of information on the combinatorial effects of low dose radiation and tobacco smoke on formation ...

  3. The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.

    Science.gov (United States)

    Khan, S A; Sachdeva, A; Naim, S; Meguid, M M; Marx, W; Simon, H; Halverson, J D; Numann, P J

    1999-10-01

    Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.

  4. Drugs Approved for Breast Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for breast cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  5. STAT3 can be activated through paracrine signaling in breast epithelial cells

    Directory of Open Access Journals (Sweden)

    Sasser A Kate

    2008-10-01

    Full Text Available Abstract Background Many cancers, including breast cancer, have been identified with increased levels of phosphorylated or the active form of Signal Transducers and Activators of Transcription 3 (STAT3 protein. However, whether the tumor microenvironment plays a role in this activation is still poorly understood. Methods Conditioned media, which contains soluble factors from MDA-MB-231 and MDA-MB-468 breast cancer cells and breast cancer associated fibroblasts, was added to MCF-10A breast epithelial and MDA-MB-453 breast cancer cells. The stimulation of phosphorylated STAT3 (p-STAT3 levels by conditioned media was assayed by Western blot in the presence or absence of neutralized IL-6 antibody, or a JAK/STAT3 inhibitor, JSI-124. The stimulation of cell proliferation in MCF-10A cells by conditioned media in the presence or absence of JSI-124 was subjected to MTT analysis. IL-6, IL-10, and VEGF levels were determined by ELISA analysis. Results Our results demonstrated that conditioned media from cell lines with constitutively active STAT3 are sufficient to induce p-STAT3 levels in various recipients that do not possess elevated p-STAT3 levels. This signaling occurs through the JAK/STAT3 pathway, leading to STAT3 phosphorylation as early as 30 minutes and is persistent for at least 24 hours. ELISA analysis confirmed a correlation between elevated levels of IL-6 production and p-STAT3. Neutralization of the IL-6 ligand or gp130 was sufficient to block increased levels of p-STAT3 (Y705 in treated cells. Furthermore, soluble factors within the MDA-MB-231 conditioned media were also sufficient to stimulate an increase in IL-6 production from MCF-10A cells. Conclusion These results demonstrate STAT3 phosphorylation in breast epithelial cells can be stimulated by paracrine signaling through soluble factors from both breast cancer cells and breast cancer associated fibroblasts with elevated STAT3 phosphorylation. The induction of STAT3 phosphorylation is

  6. Cadmium Malignantly Transforms Normal Human Breast Epithelial Cells into a Basal-like Phenotype

    OpenAIRE

    2009-01-01

    Background Breast cancer has recently been linked to cadmium exposure. Although not uniformly supported, it is hypothesized that cadmium acts as a metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the effects of chronic exposure to cadmium on the normal human breast epithelial cell line MCF-10A, which is ER-negative but can convert to ER-positive during malignant transformation. Methods Cells were continuously exposed to low-level cadmium (2.5 μM) and checked in vi...

  7. Harnessing 3D models of mammary epithelial morphogenesis: An off the beaten path approach to identify candidate biomarkers of early stage breast cancer.

    Science.gov (United States)

    Rossetti, Stefano; Bshara, Wiam; Reiners, Johanna A; Corlazzoli, Francesca; Miller, Austin; Sacchi, Nicoletta

    2016-10-01

    Regardless of the etiological factor, an aberrant morphology is the common hallmark of ductal carcinoma in situ (DCIS), which is a highly heterogeneous disease. To test if critical core morphogenetic mechanisms are compromised by different mutations, we performed proteomics analysis of five mammary epithelial HME1 mutant lines that develop a DCIS-like morphology in three dimensional (3D) culture. Here we show first, that all HME1 mutant lines share a common protein signature highlighting an inverse deregulation of two annexins, ANXA2 and ANXA8. Either ANXA2 downregulation or ANXA8 upregulation in the HME1 cell context are per se sufficient to confer a 3D DCIS-like morphology. Seemingly, different mutations impinged on a common mechanism that differentially regulates the two annexins. Second, we show that ANXA8 expression is significantly higher in DCIS tissue samples versus normal breast tissue and atypical ductal hyperplasia (ADH). Apparently, ANXA8 expression is significantly more upregulated in ER-negative versus ER-positive cases, and significantly correlates with tumor stage, grade and positive lymph node. Based on our study, 3D mammary morphogenesis models can be an alternate/complementary strategy for unraveling new DCIS mechanisms and biomarkers.

  8. Breast and Colon Cancer Family Registries

    Science.gov (United States)

    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  9. Notch in mammary gland development and breast cancer.

    Science.gov (United States)

    Politi, Katerina; Feirt, Nikki; Kitajewski, Jan

    2004-10-01

    Notch signaling has been implicated in many processes including cell fate determination and oncogenesis. In mice, the Notch1 and Notch4 genes are both targets for insertion and rearrangement by the mouse mammary tumor virus and these mutations promote epithelial mammary tumorigenesis. Moreover, expression of a constitutively active form of Notch4 in mammary epithelial cells inhibits epithelial differentiation and leads to tumor formation in this organ. These data implicate the Notch pathway in breast tumorigenesis and provide the foundation for future experiments that will aid in our understanding of the role of Notch in human breast cancer development. Here, we review studies of mammary tumorigenesis induced by Notch in mouse and in vitro culture models providing evidence that Notch activation is a causal factor in human breast cancer.

  10. Breast cancer screening in Korean woman with dense breast tissue

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hee Jung [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ko, Eun Sook [Dept. of Radiology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Yi, Ann [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-11-15

    Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results.

  11. Height and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Zhang, Ben; Shu, Xiao-Ou; Delahanty, Ryan J

    2015-01-01

    BACKGROUND: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. METHODS: We performed a met...

  12. Circadian clocks and breast cancer

    OpenAIRE

    Blakeman, Victoria; Jack L. Williams; Meng, Qing-Jun; Streuli, Charles H

    2016-01-01

    Circadian clocks respond to environmental time cues to coordinate 24-hour oscillations in almost every tissue of the body. In the breast, circadian clocks regulate the rhythmic expression of numerous genes. Disrupted expression of circadian genes can alter breast biology and may promote cancer. Here we overview circadian mechanisms, and the connection between the molecular clock and breast biology. We describe how disruption of circadian genes contributes to cancer via multiple mechanisms, an...

  13. [Therapeutic advances in breast cancer].

    Science.gov (United States)

    Pestalozzi, B C

    2006-04-01

    The treatment of breast cancer has made significant improvements during the past ten years. For early breast cancer with a clinically negative axilla sentinel node biopsy has become the preferred approach. For endocrine therapy of postmenopausal patients the selective aromatase inhibitors have become standard in metastatic as well as in early breast cancer. Trastuzumab (Herceptin) plays an important role in the treatment of HER2-positive breast cancer in the metastatic and since 2005 also in the adjuvant setting. When chemotherapy is used to treat metastatic breast cancer drug combinations are superior to monotherapy only in terms of response rates. By contrast, in the adjuvant setting combination drug therapy is the standard. New methods of tissue analysis including expression patterns of mRNA and proteins are promising research strategies to further advance the field.

  14. Decline in breast cancer mortality

    DEFF Research Database (Denmark)

    Njor, Sisse Helle; Schwartz, Walter; Blichert-Toft, Mogens

    2015-01-01

    OBJECTIVES: When estimating the decline in breast cancer mortality attributable to screening, the challenge is to provide valid comparison groups and to distinguish the screening effect from other effects. In Funen, Denmark, multidisciplinary breast cancer management teams started before screening...... was introduced; both activities came later in the rest of Denmark. Because Denmark had national protocols for breast cancer treatment, but hardly any opportunistic screening, Funen formed a "natural experiment", providing valid comparison groups and enabling the separation of the effect of screening from other...... factors. METHODS: Using Poisson regression we compared the observed breast cancer mortality rate in Funen after implementation of screening with the expected rate without screening. The latter was estimated from breast cancer mortality in the rest of Denmark controlled for historical differences between...

  15. Unemployment among breast cancer survivors

    DEFF Research Database (Denmark)

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg

    2014-01-01

    AIM: Though about 20% of working age breast cancer survivors do not return to work after treatment, few studies have addressed risk factors for unemployment. The majority of studies on occupational consequences of breast cancer focus on non-employment, which is a mixture of sickness absence......, unemployment, retirement pensions and other reasons for not working. Unemployment in combination with breast cancer may represent a particular challenge for these women. The aim of the present study is therefore to analyze the risk for unemployment in the years following diagnosis and treatment for breast...... cancer. METHOD: This study included 14,750 women diagnosed with breast cancer in Denmark 2001-2009 identified through a population-based clinical database and linked with information from Danish administrative population based registers for information on labour market affiliation, socio...

  16. Statins and breast cancer prognosis

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Lash, Timothy L; Damkier, Per

    2014-01-01

    Much preclinical and epidemiological evidence supports the anticancer effects of statins. Epidemiological evidence does not suggest an association between statin use and reduced incidence of breast cancer, but does support a protective effect of statins-especially simvastatin-on breast cancer...... recurrence. Here, we argue that the existing evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins and we advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence......, then the indications for a safe, well tolerated, and inexpensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several trial design opportunities-including candidate predictive biomarkers of statin safety and efficacy-and off er solutions to the key challenges involved...

  17. Comparison of methods for the isolation of human breast epithelial and myoepithelial cells.

    Science.gov (United States)

    Zubeldia-Plazaola, Arantzazu; Ametller, Elisabet; Mancino, Mario; Prats de Puig, Miquel; López-Plana, Anna; Guzman, Flavia; Vinyals, Laia; Pastor-Arroyo, Eva M; Almendro, Vanessa; Fuster, Gemma; Gascón, Pedro

    2015-01-01

    Two lineages, epithelial, and myoepithelial cells are the main cell populations in the normal mammary gland and in breast cancer. Traditionally, cancer research has been performed using commercial cell lines, but primary cell cultures obtained from fresh breast tissue are a powerful tool to study more reliably new aspects of mammary gland biology, including normal and pathological conditions. Nevertheless, the methods described to date have some technical problems in terms of cell viability and yield, which hamper work with primary mammary cells. Therefore, there is a need to optimize technology for the proper isolation of epithelial and myoepithelial cells. For this reason, we compared four methods in an effort to improve the isolation and primary cell culture of different cell populations of human mammary epithelium. The samples were obtained from healthy tissue of patients who had undergone mammoplasty or mastectomy surgery. We based our approaches on previously described methods, and incorporated additional steps to ameliorate technical efficiency and increase cell survival. We determined cell growth and viability by phase-contrast images, growth curve analysis and cell yield, and identified cell-lineage specific markers by flow cytometry and immunofluorescence in 3D cell cultures. These techniques allowed us to better evaluate the functional capabilities of these two main mammary lineages, using CD227/K19 (epithelial cells) and CD10/K14 (myoepithelial cells) antigens. Our results show that slow digestion at low enzymatic concentration combined with the differential centrifugation technique is the method that best fits the main goal of the present study: protocol efficiency and cell survival yield. In summary, we propose some guidelines to establish primary mammary epithelial cell lines more efficiently and to provide us with a strong research instrument to better understand the role of different epithelial cell types in the origin of breast cancer.

  18. Pregnancy associated breast cancer and pregnancy after breast cancer treatment

    OpenAIRE

    Doğer, Emek; Çalışkan, Eray; Mallmann, Peter

    2011-01-01

    Breast cancer is one of the most common cancers diagnosed during pregnancy and its frequency is increasing as more women postpone their pregnancies to their thirties and forties. Breast cancer diagnosis during pregnancy and lactation is difficult and complex both for the patient and doctors. Delay in diagnosis is frequent and treatment modalities are difficult to accept for the pregnant women. The common treatment approach is surgery after diagnosis, chemotherapy after the first trimester and...

  19. Relationship between everyday use cosmetics and female breast cancer.

    Science.gov (United States)

    Konduracka, Ewa; Krzemieniecki, Krzysztof; Gajos, Grzegorz

    2014-01-01

    Data of the European Cancer Registries indicate that the incidence of breast cancer, which is the most common cancer among women, tends to increase not only in postmenopausal but also in very young women. The potential causes of breast cancer are genetic predisposition, long -term hormonal replacement therapy, alcohol, environmental pollution, and possibly modern lifestyle. The controversial results of several studies suggest that certain everyday-use products (including cosmetic ingredients) may be linked to breast cancer. Some of these ingredients, such as ethylene oxide, have recently been classified by the International Agency for Research for Cancer as carcinogenic and mutagenic to humans, with sufficient evidence of carcinogenicity for breast cancer. Other ingredients, such as xenoestrogens, are chemicals which have an estrogen -like effect or disrupt the normal metabolism of the natural estrogen and thus act as carcinogens. Some of them have been shown to result in DNA damage in animal and human mammary epithelial cells and, therefore, have the potential to generate genomic instability in the breast tissue. Examples of xenoestrogens with such properties include parabens, aluminium salts, phthalates, or bisophenol A. No sufficient epidemiological data on humans have been published so far, and the effects of a mixture of chemicals to which women are exposed during lifetime on the incidence of breast cancer have not been investigated. However, the results of the available studies emphasize the need for analysis of adverse environmental factors, which, in addition to a genetic predisposition and natural aging, may contribute to the increased incidence of breast cancer.

  20. Three interrelated themes in current breast cancer research: gene addiction, phenotypic plasticity, and cancer stem cells

    OpenAIRE

    2011-01-01

    Recent efforts to understand breast cancer biology involve three interrelated themes that are founded on a combination of clinical and experimental observations. The central concept is gene addiction. The clinical dilemma is the escape from gene addiction, which is mediated, in part, by phenotypic plasticity as exemplified by epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition. Finally, cancer stem cells are now recognized as the basis for minimal residual disease an...

  1. Optimal breast cancer pathology manifesto.

    Science.gov (United States)

    Tot, T; Viale, G; Rutgers, E; Bergsten-Nordström, E; Costa, A

    2015-11-01

    This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way.

  2. 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

  3. An autoimmune-mediated strategy for prophylactic breast cancer vaccination.

    Science.gov (United States)

    Jaini, Ritika; Kesaraju, Pavani; Johnson, Justin M; Altuntas, Cengiz Z; Jane-Wit, Daniel; Tuohy, Vincent K

    2010-07-01

    Although vaccination is most effective when used to prevent disease, cancer vaccine development has focused predominantly on providing therapy against established growing tumors. The difficulty in developing prophylactic cancer vaccines is primarily due to the fact that tumor antigens are variations of self proteins and would probably mediate profound autoimmune complications if used in a preventive vaccine setting. Here we use several mouse breast cancer models to define a prototypic strategy for prophylactic cancer vaccination. We selected alpha-lactalbumin as our target vaccine autoantigen because it is a breast-specific differentiation protein expressed in high amounts in the majority of human breast carcinomas and in mammary epithelial cells only during lactation. We found that immunoreactivity against alpha-lactalbumin provides substantial protection and therapy against growth of autochthonous tumors in transgenic mouse models of breast cancer and against 4T1 transplantable breast tumors in BALB/c mice. Because alpha-lactalbumin is conditionally expressed only during lactation, vaccination-induced prophylaxis occurs without any detectable inflammation in normal nonlactating breast tissue. Thus, alpha-lactalbumin vaccination may provide safe and effective protection against the development of breast cancer for women in their post-child-bearing, premenopausal years, when lactation is readily avoidable and risk for developing breast cancer is high.

  4. Aluminium, antiperspirants and breast cancer.

    Science.gov (United States)

    Darbre, P D

    2005-09-01

    Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metalloestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer.

  5. Breast Cancer Center Support Grant

    Science.gov (United States)

    1999-09-01

    also occur with increased frequency in gene carriers, such prostate cancer. First-degree relatives of individuals with a BRCA1 or BRCA2 mutation have...Tumor M 36 Asian Prostate Cancer M 52 Caucasian Ovarian Cancer F 56 Caucasian Cervical Cancer F 43 Caucasian Breast Cancer F 45 Caucasian Cancer of...address transportation barriers, alternate mechanisms were put in place for provision of parking and taxi vouchers. It was expected that many of the women

  6. Apparent exchange rate for breast cancer characterization.

    Science.gov (United States)

    Lasič, Samo; Oredsson, Stina; Partridge, Savannah C; Saal, Lao H; Topgaard, Daniel; Nilsson, Markus; Bryskhe, Karin

    2016-05-01

    Although diffusion MRI has shown promise for the characterization of breast cancer, it has low specificity to malignant subtypes. Higher specificity might be achieved if the effects of cell morphology and molecular exchange across cell membranes could be disentangled. The quantification of exchange might thus allow the differentiation of different types of breast cancer cells. Based on differences in diffusion rates between the intra- and extracellular compartments, filter exchange spectroscopy/imaging (FEXSY/FEXI) provides non-invasive quantification of the apparent exchange rate (AXR) of water between the two compartments. To test the feasibility of FEXSY for the differentiation of different breast cancer cells, we performed experiments on several breast epithelial cell lines in vitro. Furthermore, we performed the first in vivo FEXI measurement of water exchange in human breast. In cell suspensions, pulsed gradient spin-echo experiments with large b values and variable pulse duration allow the characterization of the intracellular compartment, whereas FEXSY provides a quantification of AXR. These experiments are very sensitive to the physiological state of cells and can be used to establish reliable protocols for the culture and harvesting of cells. Our results suggest that different breast cancer subtypes can be distinguished on the basis of their AXR values in cell suspensions. Time-resolved measurements allow the monitoring of the physiological state of cells in suspensions over the time-scale of hours, and reveal an abrupt disintegration of the intracellular compartment. In vivo, exchange can be detected in a tumor, whereas, in normal tissue, the exchange rate is outside the range experimentally accessible for FEXI. At present, low signal-to-noise ratio and limited scan time allows the quantification of AXR only in a region of interest of relatively large tumors.

  7. The Pittsburgh Breast Cancer Consortium

    Science.gov (United States)

    2005-08-01

    Protein Autovac in Patients with Brest Cancer CPharmexa). This trial was initiated in June 2003. The PBCC accrued 5 of the planned 11 patients. This...AD_________________ Award Number: DAMD17-01-1-0374 TITLE: The Pittsburgh Breast Cancer Consortium...3. DATES COVERED 1 AUG 2001 - 31 JUL 2005 4. TITLE AND SUBTITLE The Pittsburgh Breast Cancer Consortium 5a. CONTRACT NUMBER 5b. GRANT

  8. Epigenetics and Breast Cancers

    Directory of Open Access Journals (Sweden)

    An T. Vo

    2012-01-01

    Full Text Available Several of the active compounds in foods, poisons, drugs, and industrial chemicals may, by epigenetic mechanisms, increase or decrease the risk of breast cancers. Enzymes that are involved in DNA methylation and histone modifications have been shown to be altered in several types of breast and other cancers resulting in abnormal patterns of methylation and/or acetylation. Hypermethylation at the CpG islands found in estrogen response element (ERE promoters occurs in conjunction with ligand-bonded alpha subunit estrogen receptor (Erα dimers wherein the ligand ERα dimer complex acts as a transcription factor and binds to the ERE promoter. Ligands could be 17-β-estradiol (E2, phytoestrogens, heterocyclic amines, and many other identified food additives and heavy metals. The dimer recruits DNA methyltransferases which catalyze the transfer of methyl groups from S-adenosyl-L-methionine (SAM to 5′-cytosine on CpG islands. Other enzymes are recruited to the region by ligand-ERα dimers which activate DNA demethylases to act simultaneously to increase gene expression of protooncogenes and growth-promoting genes. Ligand-ERα dimers also recruit histone acetyltransferase to the ERE promoter region. Histone demethylases such as JMJD2B and histone methyltransferases are enzymes which demethylate lysine residues on histones H3 and/or H4. This makes the chromatin accessible for transcription factors and enzymes.

  9. Diet and breast cancer

    Directory of Open Access Journals (Sweden)

    Isabelle Romieu

    2011-10-01

    Full Text Available Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability of food intake is wider,is beginning to show interesting results.Tanto la dieta como la nutrición han sido estudiadas en relación con el riesgo de cáncer de mama, dada la gran variación de incidencia de cáncer entre países, y la posibilidad de explicarla a través de la respuesta inflamatoria o inmune, así como ingesta de antioxidantes,entre otros.Hasta la fecha, ninguna asociación clara con la dieta ha sido encontrada, excepto para el consumo de alcohol, más allá del sobrepeso y del incremento de peso. Sin embargo, los estudios que se están realizando en países de mediano a bajo nivel de ingresos, con mayor variabilidad de ingesta de alimentos, comienzan a mostrar resultados interesantes.

  10. Other Considerations for Pregnancy and Breast Cancer

    Science.gov (United States)

    ... the survival of women who have had breast cancer in the past. Lactation (breast milk production) and breast-feeding should be stopped if ... methotrexate , may occur in high levels in breast milk and may harm the nursing baby. Women ... Breast cancer does not appear to harm the unborn baby. ...

  11. General Information about Breast Cancer and Pregnancy

    Science.gov (United States)

    ... the survival of women who have had breast cancer in the past. Lactation (breast milk production) and breast-feeding should be stopped if ... methotrexate , may occur in high levels in breast milk and may harm the nursing baby. Women ... Breast cancer does not appear to harm the unborn baby. ...

  12. TIMP-1 and responsiveness to gemcitabine in advanced breast cancer

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Levin Tykjær; Bjerre, Christina Annette; Ejlertsen, Bent Laursen;

    2014-01-01

    receiving GD. CONCLUSIONS: TIMP-1 status was an independent prognostic factor for OS but not TTP in patients with advanced breast cancer receiving either D or GD. There was no statistically significant interaction between TIMP-1 status and treatment, but a trend towards an incremental OS from the addition...... and predictive marker in advanced breast cancer patients receiving docetaxel (D) or gemcitabine plus docetaxel (GD). METHODS: Patients with locally advanced or metastatic breast cancer who were assigned to D or GD by participation in a randomized phase III trial were included in the study. Assessment of TIMP-1...... status was performed retrospectively on primary tumor whole-tissue sections by immunohistochemistry and tumor samples were considered positive if epithelial breast cancer cells were stained by the anti-TIMP-1 monoclonal antibody VT7. Time to progression (TTP) was the primary endpoint. Overall survival...

  13. Breast Cancer Chemotherapy and Your Heart

    Science.gov (United States)

    ... American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , Sara ... cancer treatments. Breast cancer treatments include the following: Chemotherapy involves drugs that are intended to kill the ...

  14. Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells.

    Science.gov (United States)

    Khanna, Sugandha; Darbre, Philippa D

    2013-05-01

    Parabens (alkyl esters of p-hydroxybenzoic acid) are used extensively as preservatives in consumer products, and intact esters have been measured in several human tissues. Concerns of a potential link between parabens and breast cancer have been raised, but mechanistic studies have centred on their oestrogenic activity and little attention has been paid to any carcinogenic properties. In the present study, we report that parabens can induce anchorage-independent growth of MCF-10A immortalized but non-transformed human breast epithelial cells, a property closely related to transformation and a predictor of tumour growth in vivo. In semi-solid methocel suspension culture, MCF-10A cells produced very few colonies and only of a small size but the addition of 5 × 10(-4) M methylparaben, 10(-5) M n-propylparaben or 10(-5) M n-butylparaben resulted in a greater number of colonies per dish (P paraben concentrations in human breast tissue samples from 40 mastectomies (Barr et al., 2012) showed that 22/40 of the patients had at least one of the parabens at the site of the primary tumour at or above these concentrations. To our knowledge, this is the first study to report that parabens can induce a transformed phenotype in human breast epithelial cells in vitro, and further investigation is now justified into a potential link between parabens and breast carcinogenesis.

  15. Miscellaneous syndromes and their management: occult breast cancer, breast cancer in pregnancy, male breast cancer, surgery in stage IV disease.

    Science.gov (United States)

    Colfry, Alfred John

    2013-04-01

    Surgical therapy for occult breast cancer has traditionally centered on mastectomy; however, breast conservation with whole breast radiotherapy followed by axillary lymph node dissection has shown equivalent results. Patients with breast cancer in pregnancy can be safely and effectively treated; given a patient's pregnancy trimester and stage of breast cancer, a clinician must be able to guide therapy accordingly. Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome. Several retrospective trials of surgical therapy in stage IV breast cancer have associated a survival advantage with primary site tumor extirpation.

  16. A taxonomy of epithelial human cancer and their metastases

    Directory of Open Access Journals (Sweden)

    De Moor Bart

    2009-12-01

    Full Text Available Abstract Background Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination. Methods We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures. Results Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics

  17. Breast Cancer Types: What Your Type Means

    Science.gov (United States)

    ... what treatments are most effective. Parts of the breast where cancer begins include: Milk ducts. Ductal carcinoma is the most common type of breast cancer. This type of cancer forms in the lining of a milk duct within your breast. The ducts carry breast ...

  18. Cobalt Chloride Induces Expression and Function of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Renal Proximal Tubular Epithelial Cell Line HK-2.

    Science.gov (United States)

    Nishihashi, Katsuki; Kawashima, Kei; Nomura, Takami; Urakami-Takebayashi, Yumiko; Miyazaki, Makoto; Takano, Mikihisa; Nagai, Junya

    2017-01-01

    The human breast cancer resistance protein (BCRP/ABCG2), a member of the ATP-binding cassette transporter family, is a drug transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. The cis-regulatory elements in the BCRP promoter include a hypoxia response element, i.e., the DNA binding site for hypoxia-inducible factor-1 (HIF-1). In this study, we investigated the effect of cobalt chloride, a chemical inducer of HIF-1α, on the expression and function of BCRP in human renal proximal tubular cell line HK-2. Cobalt chloride treatment significantly increased the mRNA expression of not only glucose transporter 1 (GLUT1), a typical HIF-1 target gene mRNA, but also ABCG2 mRNA in HK-2 cells. The BCRP inhibitor Ko143-sensitive accumulation of BCRP substrates such as Hoechst33342 and mitoxantrone was significantly enhanced by cobalt chloride treatment. In addition, treatment with cobalt chloride significantly increased the Ko143-sensitive accumulation of fluorescein isothiocyanate-labeled methotrexate in HK-2 cells. Furthermore, cobalt chloride treatment attenuated the cytotoxicity induced by mitoxantrone and methotrexate, which might be, at least in part, due to the increase in BCRP-mediated transport activity via HIF-1 activation. These findings indicate that HIF-1 activation protects renal proximal tubular cells against BCRP substrate-induced cytotoxicity by enhancing the expression and function of BCRP in renal proximal tubular cells.

  19. Consumer Health Education. Breast Cancer.

    Science.gov (United States)

    Arkansas Univ., Fayetteville, Cooperative Extension Service.

    This short booklet is designed to be used by health educators when teaching women about breast cancer and its early detection and the procedure for breast self-examination. It includes the following: (1) A one-page teaching plan consisting of objectives, subject matter, methods (including titles of films and printed materials), target audience,…

  20. Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells.

    Science.gov (United States)

    Cano-González, Ana; López-Rivas, Abelardo

    2016-08-01

    Transforming growth factor-beta (TGF-β) induces the epithelial to mesenchymal transition (EMT) in breast epithelial cells and plays an important role in mammary morphogenesis and breast cancer. In non-transformed breast epithelial cells TGF-β antagonizes epidermal growth factor (EGF) action and induces growth inhibition. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to participate in lumen formation during morphogenesis of human breast epithelial cells. Our previous work indicated that sensitivity of human breast epithelial cells to TRAIL can be modulated through the activation of the epidermal growth factor receptor-1 (EGFR). Here, we show that TGF-β opposes EGF-mediated sensitization to TRAIL-induced caspase-8 activation and apoptosis in non-transformed breast epithelial cells. Death-inducing signalling complex (DISC) formation by TRAIL was significantly reduced in cells treated with TGF-β. TGF-β treatment activates cytoprotective autophagy and down-regulates TRAIL-R2 expression at the cell surface by promoting the intracellular accumulation of this receptor. Lastly, we demonstrate that EMT is not involved in the inhibitory effect of TGF-β on apoptosis by TRAIL. Together, the data reveal a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis.

  1. Understanding your breast cancer risk

    Science.gov (United States)

    Skip navigation U.S. National Library of Medicine The navigation menu has been collapsed. ... page: //medlineplus.gov/ency/patientinstructions/000830.htm Understanding your breast cancer risk To use the sharing features ...

  2. Nonestrogenic drugs and breast cancer.

    Science.gov (United States)

    Danielson, D A; Jick, H; Hunter, J R; Stergachis, A; Madsen, S

    1982-08-01

    The relation between breast cancer and selected nonestrogenic drugs was evaluated in the Group Health Cooperative of Puget Sound, Seattle, Washington, a prepaid health care organization with computerized information on diagnoses and outpatient drug use. No important positive associations with breast cancer were found in a follow-up study of 302 women aged 35-74 years. These women were newly diagnosed with breast cancer in 1977-1980 and were studied in relation to exposure in the six months prior to diagnosis to one or more of the following drugs: diazepam, digitalis glycosides, medroxyprogesterone acetate, methyldopa, metronidazole, phenothiazines, tricyclic antidepressants, thiazides, thyroid/levothyroxine sodium, or spironolactone. A modest association between recent reserpine use and breast cancer was present (risk ratio = 1.7, 90% confidence interval 0.9-3.3).

  3. Palbociclib for Advanced Breast Cancer

    Science.gov (United States)

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  4. Breast cancer. Part 3: advanced cancer and psychological implications.

    Science.gov (United States)

    Harmer, Victoria

    This is the last article in this 3-part series on breast cancer. The previous two articles have outlined the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging, and treatment for breast cancer, including surgery, chemotherapy, radiotherapy and endocrine treatment. The series concludes by giving information on advanced disease, including when a patient presents late with a fungating breast lesion, or if the disease has metastasized from the breast to other organs. Lymphoedema is also described and discussed, and the latter half of this article discusses psychological implications of breast cancer, from diagnosis through the individual treatments.

  5. Role of the RANK/RANKL pathway in breast cancer.

    Science.gov (United States)

    Kiesel, Ludwig; Kohl, Annemarie

    2016-04-01

    The discovery of the OPG/RANK/RANKL pathway two decades ago has initiated novel insights into regulation of bone formation. More recently this pathway has been found to be also relevant in osteoclastic-independent mechanisms, mainly in mammary physiology and breast cancer. RANKL/RANK function is essential for epithelial cell proliferation and cellular survival as well as lobulo-alveolar development. The endogenous OPG functions as a soluble decoy receptor, binding the cytokine RANKL to prevent RANKL from activating its receptor RANK. The regulatory function of RANKL is one of the key factors in progesterone-induced proliferation of the breast. Progesterone has a direct action of progesterone on progesterone-receptor (PR) expressing cells but PR-negative cells are affected indirectly through RANKL-induced paracrine actions leading to proliferation of mammary epithelial PR-negative cells. RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Inhibition of the RANK/RANKL pathway using the monoclonal antibody denosumab can neutralize RANKL and inhibiting its interaction with its receptor RANK. Denosumab is currently used to treat osteoporosis and in prevention of skeletal related events in patients suffering from bone metastases due to solid tumors. As preclinical experiments suggest the RANKL/RANK pathway plays an important role in primary breast cancer development. The interference with the RANK/RANKL system could therefore serve as a potential target for prevention and treatment of breast cancer.

  6. Diagnosing breast cancer by using Raman spectroscopy

    Science.gov (United States)

    Haka, Abigail S.; Shafer-Peltier, Karen E.; Fitzmaurice, Maryann; Crowe, Joseph; Dasari, Ramachandra R.; Feld, Michael S.

    2005-08-01

    We employ Raman spectroscopy to diagnose benign and malignant lesions in human breast tissue based on chemical composition. In this study, 130 Raman spectra are acquired from ex vivo samples of human breast tissue (normal, fibrocystic change, fibroadenoma, and infiltrating carcinoma) from 58 patients. Data are fit by using a linear combination model in which nine basis spectra represent the morphologic and chemical features of breast tissue. The resulting fit coefficients provide insight into the chemical/morphological makeup of the tissue and are used to develop diagnostic algorithms. The fit coefficients for fat and collagen are the key parameters in the resulting diagnostic algorithm, which classifies samples according to their specific pathological diagnoses, attaining 94% sensitivity and 96% specificity for distinguishing cancerous tissues from normal and benign tissues. The excellent results demonstrate that Raman spectroscopy has the potential to be applied in vivo to accurately classify breast lesions, thereby reducing the number of excisional breast biopsies that are performed. Author contributions: M.F., J.C., R.R.D., and M.S.F. designed research; A.S.H. and K.E.S.-P. performed research; A.S.H. and M.F. analyzed data; and A.S.H. wrote the paper.This paper was submitted directly (Track II) to the PNAS office.Abbreviations: DEH, ductal epithelial hyperplasia; ROC, receiver operating characteristic; N/C, nuclear-to-cytoplasm.

  7. Metals and breast cancer.

    Science.gov (United States)

    Byrne, Celia; Divekar, Shailaja D; Storchan, Geoffrey B; Parodi, Daniela A; Martin, Mary Beth

    2013-03-01

    Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol. The metalloestrogens fall into two subclasses: metal/metalloid anions and bivalent cationic metals. The metal/metalloid anions include compounds such as arsenite, nitrite, selenite, and vanadate while the bivalent cations include metals such as cadmium, calcium, cobalt, copper, nickel, chromium, lead, mercury, and tin. The best studied metalloestrogen is cadmium. It is a heavy metal and a prevalent environmental contaminant with no known physiological function. This review addresses our current understanding of the mechanism by which cadmium and the bivalent cationic metals activate estrogen receptor-α. The review also summarizes the in vitro and in vivo evidence that cadmium functions as an estrogen and the potential role of cadmium in breast cancer.

  8. Immunoexpression analysis and prognostic value of BLCAP in breast cancer.

    Directory of Open Access Journals (Sweden)

    Irina Gromova

    Full Text Available Bladder Cancer Associated Protein (BLCAP, formerly Bc10, was identified by our laboratory as being down-regulated in bladder cancer with progression. BLCAP is ubiquitously expressed in different tissues, and several studies have found differential expression of BLCAP in various cancer types, such as cervical and renal cancer, as well as human tongue carcinoma and osteosarcoma. Here we report the first study of the expression patterns of BLCAP in breast tissue. We analyzed by immunohistochemistry tissue sections of normal and malignant specimens collected from 123 clinical high-risk breast cancer patients within the Danish Center for Translational Breast Cancer Research (DCTB prospective study dataset. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. We observed weak immunoreactivity for BLCAP in mammary epithelial cells, almost exclusively localizing to the cytoplasm and found that levels of expression of BLCAP were generally higher in malignant cells as compared to normal cells. Quantitative IHC analysis of BLCAP expression in breast tissues confirmed this differential BLCAP expression in tumor cells, and we could establish, in a 62-patient sample matched cohort, that immunostaining intensity for BLCAP was increased in tumors relative to normal tissue, in more than 45% of the cases examined, indicating that BLCAP may be of value as a marker for breast cancer. We also analyzed BLCAP expression and prognostic value using a set of tissue microarrays comprising an independent cohort of 2,197 breast cancer patients for which we had follow-up clinical information.

  9. Iodide transport and breast cancer.

    Science.gov (United States)

    Poole, Vikki L; McCabe, Christopher J

    2015-10-01

    Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer.

  10. Progress of transcription factor Twist expression in breast cancer and its biological effect

    Institute of Scientific and Technical Information of China (English)

    Tian Qian

    2016-01-01

    Breast cancer is the most common malignant tumor in women and the pathogenesis is not fully elucidated. Proliferation, invasion, epithelial-mesenchymal transition and angiogenesis are the links closely related to the occurrence and development of breast cancer. Twist is a type of basic helix-loop-helix transcription factor that can affect cell proliferation and invasion process, epithelial-mesenchymal transition process and angiogenesis process through regulating the transcription of downstream target genes. In the research, the study of transcription factor Twist expression in breast cancer and its biological effect is reviewed.

  11. Screening for Breast Cancer: Detection and Diagnosis

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Screening For Breast Cancer Detection and Diagnosis Past Issues / Summer 2014 Table of Contents Screening ... Cancer" Articles #BeBrave: A life-saving test / Breast Cancer Basics and ... and Diagnosis / Staging and Treatment / Selected National Cancer Institute Breast ...

  12. Occupational exposure and risk of breast cancer

    OpenAIRE

    FENGA, CONCETTINA

    2016-01-01

    Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic...

  13. Genomic profiling of breast cancer.

    Science.gov (United States)

    Pandey, Anjita; Singh, Alok Kumar; Maurya, Sanjeev Kumar; Rai, Rajani; Tewari, Mallika; Kumar, Mohan; Shukla, Hari S

    2009-05-01

    Genome study provides significant changes in the advancement of molecular diagnosis and treatment in Breast cancer. Several recent critical advances and high-throughput techniques identified the genomic trouble and dramatically accelerated the pace of research in preventing and curing this malignancy. Tumor-suppressor genes, proto-oncogenes, DNA-repair genes, carcinogen-metabolism genes are critically involved in progression of breast cancer. We reviewed imperative finding in breast genetics, ongoing work to segregate further susceptible genes, and preliminary studies on molecular profiling.

  14. Mammary development and breast cancer: the role of stem cells.

    Science.gov (United States)

    Ercan, C; van Diest, P J; Vooijs, M

    2011-06-01

    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often found deregulated in breast cancer. Here we provide an overview on the functional and molecular identification of mammary stem cells in the context of both normal breast development and breast cancer. We discuss the contribution of some key signaling pathways with an emphasis on Notch receptor signaling, a cell fate determination pathway often deregulated in breast cancer. A further understanding of the biological roles of the Notch pathway in mammary stem cell behavior and carcinogenesis might be relevant for the development of future therapies.

  15. Immunoexpression analysis and prognostic value of BLCAP in breast cancer

    DEFF Research Database (Denmark)

    Gromova, Irina; Gromov, Pavel; Kroman, Niels;

    2012-01-01

    patients within the Danish Center for Translational Breast Cancer Research (DCTB) prospective study dataset. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. We observed weak immunoreactivity for BLCAP in mammary epithelial cells, almost exclusively......, such as cervical and renal cancer, as well as human tongue carcinoma and osteosarcoma. Here we report the first study of the expression patterns of BLCAP in breast tissue. We analyzed by immunohistochemistry tissue sections of normal and malignant specimens collected from 123 clinical high-risk breast cancer...... localizing to the cytoplasm and found that levels of expression of BLCAP were generally higher in malignant cells as compared to normal cells. Quantitative IHC analysis of BLCAP expression in breast tissues confirmed this differential BLCAP expression in tumor cells, and we could establish, in a 62-patient...

  16. Correlation Studies on Cancer-testis Antigen TFDP3 and Epithelial-mesenchymal Transition in Breast Cancer%癌睾丸抗原TFDP3与乳腺癌上皮间质化(EMT)的相关性研究

    Institute of Scientific and Technical Information of China (English)

    肖鹏; 初明; 孙泽文; 杜毅聪; 张明波; 徐兰; 初正云; 陈雪; 何嘉勰

    2015-01-01

    目的:本研究探讨了癌睾丸抗原TFDP3与乳腺癌细胞上皮间质化(epithelial-mesenchymal transition,EMT)的关系.方法:本研究中选取了乳腺癌细胞系(MCF-10A,MCF-7,SK-BR-3和MDA-MB-231)作为研究对象,通过Western Blot的方法筛选获得了TFDP3低水平表达的乳腺癌细胞株.进一步通过质粒转染的方式构建TFDP3过表达的细胞系模型,观察TFDP3在EMT中的作用.结果:TFDP3在MCF-10A及SK-BR-3中不表达,在间质化程度较高的MDA-MB-231中高水平表达,而在上皮化程度较高的MCF-7中的低水平表达.MCF-7中过表达TFDP3后,上皮细胞标记分子E-cadherin表达下调,而间质细胞标记分子N-cadherin、Snail、Twist及细胞骨架蛋白Vimentin表达上调.结论:TFDP3可以促进乳腺癌细胞发生EMT.%Objective:To study the relationship between cancer testis antigen TFDP3 and epithelial-mesenchymal transition (EMT) in breast cancer.Methods:In this study,the breast cancer cell lines (MCF-10A,MCF-7,SK-BR-3 and MDA-MB-231) were analyzed by Western Blot to obtain a TFDP3 positive strain with lower expression.Then,we established a TFDP3 over-expression cell line by plasmid transfection,and observed the role of TFDP3 in EMT.Results:TFDP3 was not detected in MCF-10A and SK-BR-3,but at a relatively high level in MDA-MB-231 which exhibited as a mesenchymal cell line,and at a low level in MCF-7 which retains epithelial characteristics.Once MCF-7 over-expressed TFDP3,the epithelial cell marker E-cadherin was down-regulated,and the mesenchymal cell markers were up-regulated,including N-cadherin,Snail,Twist and cytoskeletal proteins Vimentin.Conclusion:TFDP3 might play an important role in promoting EMT in breast cancer cells.

  17. Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Callinice D. Capo-chichi; Kathy Q. Car; Jennifer Smedberg; Parvin Ganjei-Azar; Andrew K. Godwin; Xiang-Xi Xu

    2011-01-01

    Through advances in technology, the genetic basis of cancer has been investigated at the genomic level, and many fundamental questions have begun to be addressed. Among several key unresolved questions in cancer biology, the molecular basis for the link between nuclear deformation and malignancy has not been determined. Another hallmark of human cancer is aneuploidy; however, the causes and consequences of aneuploidy are unanswered and are hotly contested topics. We found that nuclear lamina proteins lamin A/C are absent in a significant fraction (38%) of human breast cancer tissues. Even in lamin A/C-positive breast cancer, lamin A/C expression is heterogeneous or aberrant (such as nonnuclear distribution) in the population of tumor cells, as determined by immunohistology and immunofluorescence microscopy. In most breast cancer cell lines, a significant fraction of the lamin A/Cnegative population was observed. To determine the consequences of the loss of lamin A/C, we suppressed their expression by shRNA in non-cancerous primary breast epithelial cells. Down-regulation of lamin A/C in breast epithelial cells led to morphological deformation, resembling that of cancer cells, as observed by immunofluorescence microscopy. The lamin A/C-suppressed breast epithelial cells developed aneuploidy as determined by both flow cytometry and fluorescence in situ hybridization. We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy.

  18. Vitamin D and prevention of breast cancer

    Institute of Scientific and Technical Information of China (English)

    JoEllen WELSH

    2007-01-01

    Epidemiologic data have demonstrated that breast cancer incidence is inversely correlated with indices of vitamin D status, including ultraviolet exposure, which enhances epidermal vitamin D synthesis. The vitamin D receptor (VDR) is ex-pressed in mammary epithelial cells, suggesting that vitamin D may directly influ-ence sensitivity of the gland to transformation. Consistent with this concept, in vitro studies have demonstrated that the VDR ligand, 1,25-dihydroxyvitamin D (1,25D), exerts negative growth regulatory effects on mammary epithelial ceils that contribute to maintenance of the differentiated phenotype. Furthermore, deletion of the VDR gene in mice alters the balance between proliferation and apoptosis in the mammary gland, which ultimately enhances its susceptibility to carcinogenesis.In addition, dietary supplementation with vitamin D, or chronic treatment with synthetic VDR agonists, reduces the incidence of carcinogen-induced mammary tumors in rodents. Collectively, these observations have reinforced the need to further define the human requirement for vitamin D and the molecular actions of the VDR in relation to prevention of breast cancer.

  19. Breast cancer stem cells: current advances and clinical implications.

    Science.gov (United States)

    Luo, Ming; Clouthier, Shawn G; Deol, Yadwinder; Liu, Suling; Nagrath, Sunitha; Azizi, Ebrahim; Wicha, Max S

    2015-01-01

    There is substantial evidence that many cancers, including breast cancer, are driven by a population of cells that display stem cell properties. These cells, termed cancer stem cells (CSCs) or tumor initiating cells, not only drive tumor initiation and growth but also mediate tumor metastasis and therapeutic resistance. In this chapter, we summarize current advances in CSC research with a major focus on breast CSCs (BCSCs). We review the prevailing methods to isolate and characterize BCSCs and recent evidence documenting their cellular origins and phenotypic plasticity that enables them to transition between mesenchymal and epithelial-like states. We describe in vitro and clinical evidence that these cells mediate metastasis and treatment resistance in breast cancer, the development of novel strategies to isolate circulating tumor cells (CTCs) that contain CSCs and the use of patient-derived xenograft (PDX) models in preclinical breast cancer research. Lastly, we highlight several signaling pathways that regulate BCSC self-renewal and describe clinical implications of targeting these cells for breast cancer treatment. The development of strategies to effectively target BCSCs has the potential to significantly improve the outcomes for patients with breast cancer.

  20. Microwaves for breast cancer treatments

    Directory of Open Access Journals (Sweden)

    Heba Abdelhamid Elkayal

    2015-12-01

    Full Text Available Hyperthermia is potentially an effective method for the treatment of cancer, especially breast cancer tumors. One of the most attractive attributes of hyperthermia is the possibility of providing therapeutic benefit noninvasively, minimizing side effects. To be effective, a hyperthermia treatment must selectively heat the cancerous tissue, elevating the temperature in the tumor without exposing healthy tissue to excessive temperature elevations. In this paper, a suggested simple model of Annular Phased Array (APA using eight half wavelength linear dipoles is presented. New software (COMSOL MULTIPHYSICS is used to calculate the temperature distribution inside a model of a three layered breast (skin, breast tissue, and tumor. In addition, the effect of changing the amplitude and phases of the array elements on the temperature distributions and the conditions on the values of the phases are demonstrated in order to achieve the objective of hyperthermia for breast tumor treatment.

  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. Endocrine determinants of breast density and breast cancer

    NARCIS (Netherlands)

    Verheus, M.

    2007-01-01

    Worldwide, breast cancer is the most common malignancy among females. The total breast area on a mammogram can be dived in a radiologicaly dense area (glandular and stromal tissue) and a non-dense area (mainly fat tissue). Women with a high proportion of dense breast tissue (percent breast density)

  3. A case-control study of risk factors for epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ghaem Maghami Noori F

    2001-09-01

    Full Text Available Ovarian cancer is second prevalent cancer among gynecologic malignancies and the most common type of ovarian cancer is epithelial form (85-90 percent. To detect the risk factors for the epithelial ovarian cancer, a case-control study was conducted in Valieasr hospital in 1988. In this study, 118 cases with epithelial ovarian cancer (according histological records and 240 controls without any gynecological cancer in gynecologic clinic had been interviewed. For data analysis, T-test, Chi2 test and logistic regression have been used at a =0.05 as level of significance. The mean age in cases was 50±13 and in controls was 49.9±12 years, without significant different. The mean number of pregnancies and parity in cases was less than controls, significantly (P<0.03. The mean months of breast feeding in cases was less than controls (54.9±71.2 versus 82.4±62.7 (P<0.001. The cases had a lower mean age of menarch than controls (P=0.03. 58 percent of cases and 21.3 percent of controls hadn't used any contraception methods (P=0.00001. The mean years of contraception was significantly less in cases versus controls (P<0.001. The odds ratio for epithelial ovarian cancer was 0.24 (95 percent CI: 0.13-0.48 in OCP users, 0.47 (95 percent CI: 0.005-0.43 in TL method, and was 0.41 (95 percent CI: 0.22-0.76 in other contraception methods, relative to women who hadn't used any contraception methods. This study reveals that epithelial ovarian cancer risk increases significantly with earlier menarch, decreasing number of pregnancy, deliveries duration of breast feeding and use of contraception methods. Use of contraception pill and tubal ligation method decreases risk of epithelial ovarian cancer.

  4. Propranolol and survival from breast cancer

    DEFF Research Database (Denmark)

    Cardwell, Chris R; Pottegård, Anton; Vaes, Evelien

    2016-01-01

    BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all......-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all......-analysis techniques. Dose-response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis. RESULTS: The combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all...

  5. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    Science.gov (United States)

    2015-05-01

    Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  6. Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

    Science.gov (United States)

    2017-02-17

    Estrogen Receptor Positive; Postmenopausal; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  7. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Lung cancer after treatment for breast cancer.

    Science.gov (United States)

    Lorigan, Paul; Califano, Raffaele; Faivre-Finn, Corinne; Howell, Anthony; Thatcher, Nick

    2010-12-01

    Breast cancer is the most common cancer in women, and the second most common cause of cancer death after lung cancer. Improvements in the outcome of breast cancer mean that more patients are living longer and are, therefore, at risk of developing a second malignancy. The aim of this review is to present the current understanding of the risk of lung cancer arising in patients previously treated for early stage breast cancer. We review data on the effect of treatment factors (ie, surgery type, radiotherapy technique, and adjuvant chemotherapy) and patient factors (ie, age and smoking) on the risk of developing a subsequent lung cancer. The evidence suggests that older radiotherapy techniques were associated with a substantially increased risk of developing lung cancer in the ipsilateral lung, but there is no clear evidence of an increased risk with modern techniques. Smoking is an important risk factor, and increases the risk of lung cancer in those receiving radiotherapy. Adjuvant chemotherapy is not significantly associated with an increased risk. The risk of developing lung cancer increases with time elapsed since treatment, but any effect of age at treatment is unclear.

  9. Breast Cancer and the Environment Research Program

    Science.gov (United States)

    The Breast Cancer and the Environment Research Program supports a multidisciplinary network of scientists, clinicians, and community partners to examine the effects of environmental exposures that may predispose a woman to breast cancer throughout her life.

  10. ENVIRONMENTAL FACTORS AFFECTING BREAST CANCER SUSCEPTIBILITY

    Science.gov (United States)

    Environmental Factors Affecting Breast Cancer SusceptibilitySuzanne. E. FentonUS EPA, ORD, MD-67 NHEERL, Reproductive Toxicology Division, Research Triangle Park, NC 27711.Breast cancer is still the most common malignancy afflicting women in the Western world. Alt...

  11. N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Lobna Ouldamer

    Full Text Available The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality.Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality.We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality.These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality.

  12. THERAPEUTIC OPTIONS FOR BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Milena Georgescu

    2011-12-01

    Full Text Available Breast cancer remains a major public health problem, being the second cause of cancer death in women. There is a marked tendency to restrict the extension of surgical gesture, which directly leads to two different attitudes: radical surgery and conservative surgery, to which, at least in our country, there are still some delays. Prospective and retrospective studies have shown that, in 20 years, conservative and radical therapy had about the same rate of survival and disease-free interval, at least for stage I and II breast cancer, the only real counterargument against conservative surgery being that, in principle, the higher rate of recurrence local constraint can be solved by postoperative radiotherapy. Finally, the survival rate is the main parameter of evaluation, assessing the effectiveness of the treatment in breast cancer, and in all its other forms.

  13. TIMP-1 and responsiveness to gemcitabine in advanced breast cancer

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Levin Tykjær; Bjerre, Christina Annette; Ejlertsen, Bent Laursen

    2014-01-01

    classified as cancer cell TIMP-1 positive. No significant difference for TTP between TIMP-1 positive versus TIMP-1 negative patients was observed in multivariate analysis, and RR did not differ according to TIMP-1 status. However, patients with TIMP-1 positive tumors had a significant reduction in OS events...... and predictive marker in advanced breast cancer patients receiving docetaxel (D) or gemcitabine plus docetaxel (GD). METHODS: Patients with locally advanced or metastatic breast cancer who were assigned to D or GD by participation in a randomized phase III trial were included in the study. Assessment of TIMP-1...... status was performed retrospectively on primary tumor whole-tissue sections by immunohistochemistry and tumor samples were considered positive if epithelial breast cancer cells were stained by the anti-TIMP-1 monoclonal antibody VT7. Time to progression (TTP) was the primary endpoint. Overall survival...

  14. Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

    Science.gov (United States)

    2017-01-24

    Bilateral Breast Carcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma; Unilateral Breast Carcinoma

  15. CD147, CD44, and the epidermal growth factor receptor (EGFR) signaling pathway cooperate to regulate breast epithelial cell invasiveness.

    Science.gov (United States)

    Grass, G Daniel; Tolliver, Lauren B; Bratoeva, Momka; Toole, Bryan P

    2013-09-06

    The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777-788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer.

  16. Management of recurrent epithelial ovarian cancer

    Science.gov (United States)

    Moreno-Eutimio, Mario Adan; Acosta-Altamirano, Gustavo; Vargas-Aguilar, Víctor Manuel

    2014-01-01

    Epithelial ovarian cancer is the fifth most common cancer in women. It is usually diagnosed at an advanced stage and is the leading cause of death from gynecologic cancers in women. The overall survival rate at five years is 50% and its treatment is still poor. We need new treatments for patients with recurrent ovarian cancer who are incurable with current management. We review the effectiveness of new biological agents and morbidity and mortality of cytoreductive surgery. Since the hyperthermic increases the effectiveness of chemotherapy and the chance of survival, hyperthermic intraperitoneal chemotherapy has been proven to be a promising option, however it still requires further study to be the standard treatment. PMID:25207212

  17. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    Science.gov (United States)

    2016-10-25

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  18. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Söletormos, Georg; Duffy, Michael J; Othman Abu Hassan, Suher

    2016-01-01

    OBJECTIVE: To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. METHODS: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. RESULTS: Because of its low...... for secondary cytoreductive surgery. CONCLUSIONS: At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4...

  19. Withaferin A Inhibits Experimental Epithelial-Mesenchymal Transition in MCF-10A Cells and Suppresses Vimentin Protein Level in Vivo in Breast Tumors

    OpenAIRE

    Lee, Joomin; Hahm, Eun-Ryeong; Marcus, Adam I.; Singh, Shivendra V.

    2013-01-01

    We have shown previously that withaferin A (WA), a bioactive component of the medicinal plant Withania somnifera, inhibits growth of cultured and xenografted human breast cancer cells and prevents breast cancer development and pulmonary metastasis incidence in a transgenic mouse model. The present study was undertaken to determine if the anticancer effect of WA involved inhibition of epithelial-mesenchymal transition (EMT). Experimental EMT induced by exposure of MCF-10A cells to tumor necros...

  20. Internet Use and Breast Cancer Survivors

    Science.gov (United States)

    Muhamad, Mazanah; Afshari, Mojgan; Mohamed, Nor Aini

    2011-01-01

    A survey was administered to 400 breast cancer survivors at hospitals and support group meetings in Peninsular Malaysia to explore their level of Internet use and factors related to the Internet use by breast cancer survivors. Findings of this study indicated that about 22.5% of breast cancer survivors used Internet to get information about breast…

  1. Search for new breast cancer susceptibility genes

    NARCIS (Netherlands)

    Oldenburg, Rogier Abel

    2008-01-01

    This thesis describes the search for new high-risk breast cancer susceptibility genes by linkage analysis. To date 20-25% of familial breast cancer is explained by mutations in the high-risk BRCA1 and BRCA2 breast cancer susceptibility genes. For the remaining families the genetic etiology is unknow

  2. Fruits and vegetables and the risk of epithelial cancer

    NARCIS (Netherlands)

    Jansen, M.C.J.F.

    2001-01-01

    In this thesis, prospective studies on fruit and vegetable consumption in relation to epithelial cancer risk were described. The main research question was whether higher intakes were related to lower risks of epithelial cancers, mainly of lung cancer.In the Seven Countries Study, at the population

  3. The T box transcription factor TBX2 promotes epithelial-mesenchymal transition and invasion of normal and malignant breast epithelial cells.

    Directory of Open Access Journals (Sweden)

    Bin Wang

    Full Text Available The T box transcription factor TBX2, a master regulator of organogenesis, is aberrantly amplified in aggressive human epithelial cancers. While it has been shown that overexpression of TBX2 can bypass senescence, a failsafe mechanism against cancer, its potential role in tumor invasion has remained obscure. Here we demonstrate that TBX2 is a strong cell-autonomous inducer of the epithelial-mesenchymal transition (EMT, a latent morphogenetic program that is key to tumor progression from noninvasive to invasive malignant states. Ectopic expression of TBX2 in normal HC11 and MCF10A mammary epithelial cells was sufficient to induce morphological, molecular, and behavioral changes characteristic of EMT. These changes included loss of epithelial adhesion and polarity gene (E-cadherin, ß-catenin, ZO1 expression, and abnormal gain of mesenchymal markers (N-cadherin, Vimentin, as well as increased cell motility and invasion. Conversely, abrogation of endogenous TBX2 overexpression in the malignant human breast carcinoma cell lines MDA-MB-435 and MDA-MB-157 led to a restitution of epithelial characteristics with reciprocal loss of mesenchymal markers. Importantly, TBX2 inhibition abolished tumor cell invasion and the capacity to form lung metastases in a Xenograft mouse model. Meta-analysis of gene expression in over one thousand primary human breast tumors further showed that high TBX2 expression was significantly associated with reduced metastasis-free survival in patients, and with tumor subtypes enriched in EMT gene signatures, consistent with a role of TBX2 in oncogenic EMT. ChIP analysis and cell-based reporter assays further revealed that TBX2 directly represses transcription of E-cadherin, a tumor suppressor gene, whose loss is crucial for malignant tumor progression. Collectively, our results uncover an unanticipated link between TBX2 deregulation in cancer and the acquisition of EMT and invasive features of epithelial tumor cells.

  4. Appraisal of progenitor markers in the context of molecular classification of breast cancers.

    Science.gov (United States)

    Haviv, Izhak

    2011-01-25

    Clinical management of breast cancer relies on case stratification, which increasingly employs molecular markers. The motivation behind delineating breast epithelial differentiation is to better target cancer cases through innate sensitivities bequeathed to the cancer from its normal progenitor state. A combination of histopathological and molecular classification of breast cancer cases suggests a role for progenitors in particular breast cancer cases. Although a remarkable fraction of the real tissue repertoire is maintained within a population of independent cell line cultures, some steps that are closer to the terminal differentiation state and that form a majority of primary human breast tissues are missing in the cell line cultures. This raises concerns about current breast cancer models.

  5. 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

  6. Overexpression of centromere protein H is significantly associated with breast cancer progression and overall patient survival

    Institute of Scientific and Technical Information of China (English)

    Wen-Ting Liao; Yan Feng; Men-Lin Li; Guang-Lin Liu; Man-Zhi Li; Mu-Sheng Zeng; Li-Bing Song

    2011-01-01

    Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H (CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Westem blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134 (43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage (P = 0.001),T classification (P = 0.032),N classification (P =0.018),and Ki-67 (P<0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.

  7. Secretory breast cancer. Case report.

    Science.gov (United States)

    Lombardi, A; Maggi, S; Bersigotti, L; Lazzarin, G; Nuccetelli, E; Amanti, C

    2013-04-01

    Secretory carcinoma of the breast is a rare tumor initially described in children but occurring equally in adult population. This unusual breast cancer subtype has a generally favorable prognosis, although several cases have been described in adults with increased aggressiveness and a risk of metastases. However, surgery is still considered the most appropriate treatment for this pathology. We describe the case of a 50 -year-old woman who has undergone a breast conservative surgery for a little tumor, preoperatively diagnosticated by a fine needle aspiration biopsy (FNAB) as a well differentiated infiltrating carcinoma.

  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. Circulating tumour cells lacking cytokeratin in breast cancer: the importance of being mesenchymal.

    Science.gov (United States)

    Gradilone, Angela; Raimondi, Cristina; Nicolazzo, Chiara; Petracca, Arianna; Gandini, Orietta; Vincenzi, Bruno; Naso, Giuseppe; Aglianò, Anna Maria; Cortesi, Enrico; Gazzaniga, Paola

    2011-05-01

    Circulating tumour cells (CTCs) are independent predictor of prognosis in metastatic breast cancer. Nevertheless, in one third of patients, circulating tumour cells are undetected by conventional methods. Aim of the study was to assess the prognostic value of circulating tumour cells expressing mesenchymal markers in metastatic breast cancer patients. We isolated CTC from blood of 55 metastatic breast cancer patients. CTC were characterized for cytokeratins and markers of epithelial mesenchymal transition. The gain of mesenchymal markers in CTC was correlated to prognosis of patients in a follow-up of 24 months. The presence of mesenchymal markers on CTC more accurately predicted worse prognosis than the expression of cytokeratins alone. Because of the frequent loss of epithelial antigens by CTC, assays targeting epithelial antigens may miss the most invasive cell population. Thus, there is an urgent need to improve detection methods to identify CTC which undergone epithelial mesenchymal transition program.

  10. The Role of SDF-1alpha and CXCR4 in Metastatic Breast Cancer

    Science.gov (United States)

    2006-08-01

    cancer cells. Nutr Cancer 2004;48:84–94. 5. Rahman KM, Aranha O, Glazyrin A, Chinni SR, Sarkar FH. Translocation of Bax to mitochondria induces...KM, Aranha O, Sarkar FH. Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in non- tumorigenic breast epithelial cells. Nutr Cancer...Rahman KM, Aranha O, Glazyrin A, et al. Translocation of Bax to mitochondria induces apoptotic cell death in indole-3-carbinol (I3C) treated breast

  11. Inflammatory breast cancer: an overview.

    Science.gov (United States)

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

    2015-02-01

    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 multimodal therapeutic approach has significantly improved patient survival. However, the median overall survival among women with IBC is still poor. By elucidating the biologic characteristics of IBC, new treatment options may become available. We performed a comprehensive review of the English-language literature on IBC through computerized literature searches. The objective of the current review is to present an overview of the literature related to the biology, imaging and multidisciplinary treatment of inflammatory breast cancer.

  12. Reconstruction for breast cancer in a nutshell.

    Science.gov (United States)

    Harmer, Victoria

    Breast cancer is a disease many will experience. Depending on the size of the cancer, the size of the host breast, and whether it is multi-focal, a mastectomy may be recommended as part of the treatment. If this is the case, an immediate breast reconstruction may be offered. This article will describe the three main types of breast reconstruction and discuss pertinent issues regarding this, including complications, surgery to the other (contraleteral) breast and potential psychological implications of this surgery.

  13. Occupational exposure and risk of breast cancer.

    Science.gov (United States)

    Fenga, Concettina

    2016-03-01

    Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer.

  14. Field cancerization in mammary carcinogenesis - Implications for prevention and treatment of breast cancer.

    Science.gov (United States)

    Rivenbark, Ashley G; Coleman, William B

    2012-12-01

    The natural history of breast cancer unfolds with the development of ductal carcinoma in situ (DCIS) in normal breast tissue, and evolution of this pre-invasive neoplasm into invasive cancer. The mechanisms that drive these processes are poorly understood, but evidence from the literature suggests that mammary carcinogenesis may occur through the process of field cancerization. Clinical observations are consistent with the idea that (i) DCIS may arise in a field of altered breast epithelium, (ii) narrow surgical margins do not remove the entire altered field (contributing to recurrence and/or disease progression), and (iii) whole-breast radiation therapy is effective in elimination of the residual field of altered cells adjacent to the resected DCIS. Molecular studies suggest that the field of altered breast epithelial cells may carry cancer-promoting genetic mutations (or other molecular alterations) or cancer promoting epimutations (oncogenic alterations in the epigenome). In fact, most breast cancers develop through a succession of molecular events involving both genetic mutations and epimutations. Hence, in hereditary forms of breast cancer, the altered field reflects the entire breast tissue which is composed of cells with a predisposing molecular lesion (such as a BRCA1 mutation). In the example of a BRCA1-mutant patient, it is evident that local resection of a DCIS lesion or localized but invasive cancer will not result in elimination of the altered field. In sporadic breast cancer patients, the mechanistic basis for the altered field may not be so easily recognized. Nonetheless, identification of the nature of field cancerization in a given patient may guide clinical intervention. Thus, patients with DCIS that develops in response to an epigenetic lesion (such as a hypermethylation defect affecting the expression of tumor suppressor genes) might be treated with epigenetic therapy to normalize the altered field and reduce the risk of secondary occurrence of

  15. Epithelial ovarian cancer: testing the 'androgens hypothesis'.

    Science.gov (United States)

    Olsen, Catherine M; Green, Adèle C; Nagle, Christina M; Jordan, Susan J; Whiteman, David C; Bain, Christopher J; Webb, Penelope M

    2008-12-01

    In 1998, Risch proposed a hypothesis for the pathogenesis of ovarian cancer relating to the role of androgens in stimulating epithelial cell proliferation. Although this hypothesis has been widely discussed, direct evidence to support it is scant. To address this issue, we have conducted a detailed analysis of factors possibly associated with high circulating levels of androgens, including polycystic ovary syndrome (PCOS), hirsutism and acne (all clinically associated with hyperandrogenism) using the data collected in an Australia-wide, population-based case-control study. Cases aged 18-79 years with a new diagnosis of invasive epithelial ovarian cancer (n=1276) or borderline malignant tumour (n=315) were identified through a network of clinics and cancer registries throughout Australia. Controls (n=1508) were selected from the National Electoral Roll. Women self-reported a history of PCOS, acne, hirsutism and also use of testosterone supplements or the androgenic medication Danazol. We found no evidence that a history of PCOS, acne or hirsutism was associated with ovarian cancer overall, or with specific subtypes, with the exception of serous borderline tumours that were positively associated with a history of PCOS (OR 2.6; 95% CI 1.0-6.1). Women who had ever used testosterone supplements had an increased risk of ovarian cancer (OR 3.7; 95% CI 1.1-12.0); however, use of the androgenic medication Danazol did not increase risk (OR 1.0; 95% CI 0.4-2.9). Overall, our results do not support the hypothesis that androgen-related disorders increase the risk of ovarian cancer.

  16. Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

    Science.gov (United States)

    2017-01-17

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  17. An update on inflammatory breast cancer

    Directory of Open Access Journals (Sweden)

    P. Thapaliya

    2011-12-01

    Full Text Available Inflammatory breast cancer is one of the most aggressive forms of breast cancer. Once considered to be a uniformly fatal disease, treatment of this entity has evolved significantly over the last two decades. In this article, we review the epidemiology, pathology, biologic underpinnings, radiologic advances, and treatment modalities for inflammatory breast cancer. Updates in surgical therapy, medical oncologic therapy and radiation therapy are reviewed. Emphasis is on cutting edge information regarding inflammatory breast cancer. The management of inflammatory breast cancer is best served by a multidisciplinary team. Continued research into molecular pathways and potential targets is imperative. Future clinical trials should include evaluation of conventional therapy with targeted therapies.

  18. Breast cancer epidemiology and risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Broeders, M. J. M.; Verbeek, A. L. M. [Nijmegen, Univ. (Netherlands). Dept. of Epidemiology

    1997-09-01

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form may therefore have more influence on one form of breast cancer than another. So far though, as shown in their summary of current knowledge on established and dubious risk factors, no risk factors have been identified that can explain a major part of the incidence. Efforts to identify other ways for primary prevention have also been discouraging, even though breast cancer is one of the most investigated tumours world-wide. Thus, at this point i time, the most important strategy to reduce breast cancer mortality is early detection through individual counselling and organised breast screening programs. The recent isolation of breast cancer susceptibility genes may introduce new ways to reduce the risk of breast cancer in a small subset of women.

  19. 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...

  20. Breast Cancer (For Kids)

    Science.gov (United States)

    ... or sacs) or they can be due to normal breast changes associated with hormone changes or aging. Girls who are beginning puberty might notice a lump underneath the nipple when their breasts start developing. Usually, this is a normal. You can ask a parent or your doctor ...

  1. Ultrasound screening of contralateral breast after surgery for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Ja [Department of Radiology, Seoul Metropolitan Government Seoul National University, Boramae Medical Center (Korea, Republic of); Chung, Se-Yeong; Chang, Jung Min; Cho, Nariya [Department of Radiology, Seoul National University Hospital (Korea, Republic of); Han, Wonshik [Department of Surgery, Seoul National University Hospital (Korea, Republic of); Moon, Woo Kyung, E-mail: moonwk@snu.ac.kr [Department of Radiology, Seoul National University Hospital (Korea, Republic of)

    2015-01-15

    Highlights: • The addition of supplemental US to mammography depicted additional 5.0 cancers per 1000 postoperative women. • Positive biopsy rate of mammography-detected lesions was 66.7% (4 of 6) and that of US-detected lesions was 40.0% (6 of 15). • US can be helpful to detect mammographically occult breast cancer in the contralateral breast in women with previous history of cancer and dense breast. - Abstract: Objective: To determine whether supplemental screening ultrasound (US) to mammography could improve cancer detection rate of the contralateral breast in patients with a personal history of breast cancer and dense breasts. Materials and methods: During a one-year study period, 1314 screening patients with a personal history of breast cancer and dense breasts simultaneously underwent mammography and breast US. BI-RADS categories were given for mammography or US-detected lesions in the contralateral breast. The reference standard was histology and/or 1-year imaging follow-up, and the cancer rate according to BI-RADS categories and cancer detection rate and positive biopsy rate according to detection modality were analyzed. Results: Of 1314 patients, 84 patients (6.4%) were categorized as category 3 with one interval cancer and one cancer which was upgraded to category 4A after 6-month follow-up US (2.5% cancer rate, 95% CIs 1.5–9.1%). Fifteen patients (1.1%) had category 4A or 4B lesions in the contralateral breast. Four lesions were detected on mammography (two lesions were also visible on US) and 11 lesions were detected on US and 5 cancers were confirmed (33.3%, 95% CIs 15.0–58.5%). Six patients (0.5%) had category 4C lesions, 2 detected on mammography and 4 on US and 4 cancers were confirmed (66.7%, 95% CIs 29.6–90.8%). No lesions were categorized as category 5 in the contralateral breast. Cancer detection rate by mammography was 3.3 per 1000 patients and that by US was 5.0 per 1000 patients, therefore overall cancer detection rate by

  2. 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.

  3. Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants

    Directory of Open Access Journals (Sweden)

    Kai-Hung Wang

    2016-01-01

    Full Text Available We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate is a better medium to grow human breast epithelial cells. The results clearly show that the K-NAC medium is a superior medium for prolonged growth (cumulative population doubling levels ranged from 30 to 40 of normal breast epithelial cells that expressed stem cell phenotypes. The characteristics of these mammary stem cells include deficiency in gap junctional intercellular communication, expression of Oct-4, and the ability to differentiate into basal epithelial cells and to form organoid showing mammary ductal and terminal end bud-like structures. Thus, this new method of growing Type I HBECs will be very useful in future studies of mammary development, breast carcinogenesis, chemoprevention, and cancer therapy.

  4. Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines.

    Directory of Open Access Journals (Sweden)

    Guillaume Vares

    Full Text Available Exposure to ionizing radiation was shown to result in an increased risk of breast cancer. There is strong evidence that steroid hormones influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells (CSCs. In order to assess whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured by flow cytometry the proportion of CSCs in irradiated breast cancer cell lines after progesterone and estrogen treatment. Progesterone stimulated the expansion of the CSC compartment both in progesterone receptor (PR-positive breast cancer cells and in PR-negative normal cells. In MCF10A normal epithelial PR-negative cells, progesterone-treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the downregulation of miR-22 and miR-29c expression, which resulted in increased proportions of radiation-resistant tumor-initiating CSCs.

  5. Surgery for advanced epithelial ovarian cancer.

    Science.gov (United States)

    Hacker, Neville F; Rao, Archana

    2016-10-20

    Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational. In recent years, there has been increasing use of neoadjuvant chemotherapy and interval cytoreductive surgery in patients with poor performance status, which is usually due to large volume ascites and/or large pleural effusions. Neoadjuvant chemotherapy reduces the post-operative morbidity, but if the tumour responds well to the chemotherapy, the inflammatory response makes the surgery more difficult. Post-operative morbidity is generally tolerable, but increases in older patients, and in those having multiple, aggressive surgical procedures, such as bowel resection or diaphragmatic stripping. Primary cytoreductive surgery should be regarded as the gold standard for most patients until a test is developed which would allow the prediction of platinum resistance pre-operatively.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  7. Tight junctions: a barrier to the initiation and progression of breast cancer?

    LENUS (Irish Health Repository)

    Brennan, Kieran

    2010-01-01

    Breast cancer is a complex and heterogeneous disease that arises from epithelial cells lining the breast ducts and lobules. Correct adhesion between adjacent epithelial cells is important in determining the normal structure and function of epithelial tissues, and there is accumulating evidence that dysregulated cell-cell adhesion is associated with many cancers. This review will focus on one cell-cell adhesion complex, the tight junction (TJ), and summarize recent evidence that TJs may participate in breast cancer development or progression. We will first outline the protein composition of TJs and discuss the functions of the TJ complex. Secondly we will examine how alterations in these functions might facilitate breast cancer initiation or progression; by focussing on the regulatory influence of TJs on cell polarity, cell fate and cell migration. Finally we will outline how pharmacological targeting of TJ proteins may be useful in limiting breast cancer progression. Overall we hope to illustrate that the relationship between TJ alterations and breast cancer is a complex one; but that this area offers promise in uncovering fundamental mechanisms linked to breast cancer progression.

  8. Association of breast cancer risk loci with breast cancer survival

    NARCIS (Netherlands)

    Barrdahl, Myrto; Canzian, Federico; Lindström, Sara; Shui, Irene; Black, Amanda; Hoover, Robert N.; Ziegler, Regina G.; Buring, Julie E.; Chanock, Stephen J.; Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Giles, Graham G.; Haiman, Christopher; Henderson, Brian E.; Hankinson, Susan; Hunter, David J.; Joshi, Amit D.; Kraft, Peter; Lee, I. Min; Le Marchand, Loic; Milne, Roger L.; Southey, Melissa C.; Willett, Walter; Gunter, Marc; Panico, Salvatore; Sund, Malin; Weiderpass, Elisabete; Sánchez, María José; Overvad, Kim; Dossus, Laure; Peeters, Petra H.; Khaw, Kay Tee; Trichopoulos, Dimitrios; Kaaks, Rudolf; Campa, Daniele

    2015-01-01

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of eviden

  9. Genomic analysis of epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    John Farley; Laurent L Ozbun; Michael J Birrer

    2008-01-01

    Ovarian cancer is a major health problem for women in the United States.Despite evidence of considerable heterogeneity,most cases of ovarian cancer are treated in a similar fashion.The molecular basis for the clinicopathologic characteristics of these tumors remains poorly defined.Whole genome expression profiling is a genomic tool,which can identify dysregulated genes and uncover unique sub-classes of tumors.The application of this technology to ovarian cancer has provided a solid molecular basis for differences in histology and grade of ovarian tumors.Differentially expressed genes identified pathways implicated in cell proliferation,invasion,motility,chromosomal instability,and gene silencing and provided new insights into the origin and potential treatment of these cancers.The added knowledge provided by global gene expression profiling should allow for a more rational treatment of ovarian cancers.These techniques are leading to a paradigm shift from empirical treatment to an individually tailored approach.This review summarizes the new genomic data on epithelial ovarian cancers of different histology and grade and the impact it will have on our understanding and treatment of this disease.

  10. Cells of Origin of Epithelial Ovarian Cancers

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0280 TITLE: Cells of Origin of Epithelial Ovarian Cancers PRINCIPAL INVESTIGATOR: Zhe Li, PhD CONTRACTING...Xie, Zhe Li 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: zli4@rics.bwh.harvard.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND...Lined Inclusion Cysts or Teratomas. PLoS ONE 8, e65067. Sherman-Baust, C.A., Kuhn, E., Valle, B.L., Shih Ie, M., Kurman, R.J., Wang , T.L., Amano, T

  11. THE RELATION BETWEEN BREAST FEEDING AND BREAST CANCER

    Directory of Open Access Journals (Sweden)

    M.Alavi Naini

    1998-03-01

    Full Text Available Second to the cardiovascular disease, cancer is the main cause of death in Iran. In this study some of the risk factors of breast cancer; especially the ones related to breastfeeding have been assessed. The study was a retrospective study of 100 women with breast cancer. The most important risk factors in breast cancer were number of children, age of mother on the first pregnancy. The result showed that the increase of breast cancer was related to women who stopped breastfeeding before age 24 months. Breastfeeding for more than 12 months will reduce the incidence of breast cancer by 25%. In general there was a reverse relationship between duration of breastfeeding and risk of cancer in premonopausal, but not in postmenopausal women.

  12. 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

  13. 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...

  14. Dietary fiber and breast cancer.

    Science.gov (United States)

    Cohen, L A

    1999-01-01

    The Fiber Hypothesis which had its origins in the work of Burkitt and others in the early 1970's, focussed largely on fiber's beneficial effects on colon cancer and disorders of the gastric intestinal tract. In the 1980's it was proposed that fiber may also have beneficial effects on breast cancer and a rational for this was proposed involving modulation, by fiber, of the enterohepatic recirculation of estrogens. In the following the evidence from epidemiology, clinical interventions and animal model studies, supporting a role for fiber in breast cancer is critically reviewed. Evidence from animal model studies support the notion that supplementary fiber inhibits chemically-induced mammary tumorigenesis but do not support an estrogen-based mechanism. Some studies in human populations suggest modulation by estrogens and some do not. The aggregate data point to minor constituents present in fiber, such as isoflavones and phytate as the biologically active components of fiber which may be responsible for its anti cancer effects.

  15. Breast Cancer in Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Tessier Cloutier, B; Clarke, A E; Ramsey-Goldman, R

    2013-01-01

    Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries.......Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries....

  16. Targeting aberrant expression of Notch-1 in ALDH(+) cancer stem cells in breast cancer.

    Science.gov (United States)

    Pal, Deeksha; Kolluru, Venkatesh; Chandrasekaran, Balaji; Baby, Becca V; Aman, Masarath; Suman, Suman; Sirimulla, Suman; Sanders, Mary Ann; Alatassi, Houda; Ankem, Murali K; Damodaran, Chendil

    2017-03-01

    We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues. Injection of BCSC (ALDH(+) and CD44(+) /CD22(-) ) cells resulted in aggressive tumor growth in athymic mice versus ALDH(-) cells. The ALDH(+) and CD44(+) /CD22(-) tumors grow rapidly and are larger than ALDH(-) tumors which were slow growing and smaller. Molecularly, ALDH(+) tumors expressed higher expression of Notch-1 and EMT markers than ALDH(-) tumors. Oral administration of the naturally occurring Psoralidin (Pso, 25 mg/kg of body weight) significantly inhibited the growth in ALDH(+) and ALDH(-) tumors as well. Psoralidin inhibited Notch-1 mediated EMT activation in ALDH(+) and ALDH(-) tumors-this confirms our in vitro findings. Our results suggest that Notch-1 could be an attractive target and inhibition of Notch-1 by Psoralidin may prevent pathogenesis of breast cancer as well as metastasis. © 2016 Wiley Periodicals, Inc.

  17. Hereditary breast and ovarian cancer

    DEFF Research Database (Denmark)

    Nielsen, Finn Cilius; van Overeem Hansen, Thomas; Sørensen, Claus Storgaard

    2016-01-01

    Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....

  18. Risk, characteristics, and prognosis of breast cancer after Hodgkin's lymphoma

    OpenAIRE

    Veit-rubin, Nikolaus; Rapiti Aylward, Elisabetta; Usel, Massimo; Benhamou, Simone; Vinh Hung, Vincent; Vlastos, Georges; Bouchardy Magnin, Christine

    2012-01-01

    Patients with breast cancer after Hodgkin's lymphoma were compared with patients with other breast cancers using the Surveillance, Epidemiology and End Results dataset. Hodgkin's lymphoma survivors had a higher risk for breast cancer, more aggressive breast cancers, a higher risk for a second breast cancer, and a poorer prognosis.

  19. What You Need to Know about Breast Cancer

    Science.gov (United States)

    ... Publications Reports What You Need To Know About™ Breast Cancer This booklet is about breast cancer. Learning about your cancer can help you take ... This booklet covers: Basics about breast anatomy and breast cancer Treatments for breast cancer, including taking part in ...

  20. Risk of primary non-breast cancer after female breast cancer by age at diagnosis

    DEFF Research Database (Denmark)

    Mellemkjær, Lene; Christensen, Jane; Frederiksen, Kirsten Skovsgaard;

    2011-01-01

    Women diagnosed with breast cancer at young age have been shown to be at higher risk of developing a new primary cancer than women diagnosed at older ages, but little is known about whether adjustment for calendar year of breast cancer diagnosis, length of follow-up, and/or breast cancer treatment...

  1. 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

  2. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2013-09-01

    CSF. J Clin Invest 117, 1902 (Jul, 2007). 32. H. Yamaguchi et al., Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus . J Leukoc Biol 83, 1300 (May, 2008). ...comprehensive and systematic manner is the underlying principle of my goal to develop ’rational combination immunotherapy’ for breast cancer, one

  3. Mouse Stirs up Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Helen Pilcher; 孙雯

    2004-01-01

    @@ The humble house mouse could be more dangerous than we thought,according to a study that suggests a rodent① virus plays a role in the development of breast cancer. But the finding is contentious② and reignites③ a long-standing④wrangle⑤ about the potential⑥ causes of the disease.

  4. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...

  5. Genetic determinants of breast cancer

    NARCIS (Netherlands)

    A.M. Gonzalez-Zuloeta Ladd (Angela)

    2007-01-01

    textabstractBreast cancer is the most common malignancy in women in the Western world and it is estimated that women who survive to the age of 85 years will have a 1 in 9 lifetime probability of developing this type of neoplasia (1, 2). The degree of risk is not spread homogeneously across the gener

  6. Breast Cancer Startup Challenge winners

    Science.gov (United States)

    Ten winners of a world-wide competition to bring emerging breast cancer research technologies to market faster were announced today by the Avon Foundation for Women, in partnership with NCI and the Center for Advancing Innovation (CAI). Avon is providing

  7. Breast cancer with inguinal node recurrence

    Directory of Open Access Journals (Sweden)

    Shikha Goyal

    2015-03-01

    Full Text Available Surgery and irradiation for breast cancer may interfere with conventional pathways of spread, leading to bizarre patterns of dissemination through lymphatics or through hematogenous route. Lymphoscintigraphic studies may help identify nodal involvement. Other possible reasons could be occurrence of primary breast cancer in accessory breast tissue retained in the vulva following involution of milk line. We describe a case of triple negative breast cancer, who developed contralateral breast cancer during treatment. Three years later, she developed isolated inguinal nodal metastases, which responded to local radiotherapy and chemotherapy. However, the patient relapsed after 2 years and could not be salvaged thereafter.

  8. Neoplastic transformation of breast epithelial cells by genotoxic stress

    Directory of Open Access Journals (Sweden)

    Raman Venu

    2010-06-01

    Full Text Available Abstract Background Exposure to genotoxic stresses such as radiation and tobacco smoke can cause increased cancer incidence rate as reflected in an in depth meta-analysis of data for women and breast cancer incidence. Published reports have indicated that exposures to low dose radiation and tobacco smoke are factors that contribute to the development of breast cancer. However, there is a scarcity of information on the combinatorial effects of low dose radiation and tobacco smoke on formation and progression of breast cancer. The combination of these two genotoxic insults can induce significant damage to the genetic material of the cells resulting in neoplastic transformation. Methods To study the effects of low dose ionizing radiation and tobacco smoke on breast cells, MCF 10A cells were treated either with radiation (Rad - 0.1 Gray or cigarette smoke condensate (Csc - 10 microgram/ml of medium or a combination of Rad + Csc. Following treatments, cells were analyzed for cell cycle distribution patterns and the ability to extrude the Hoechst 33342 dye. In addition, in vitro invasion and migration as well as mammosphere formation assays were performed. Finally, differential gene expression profiles were generated from the individual and combination treatment. Results Exposure of MCF 10A cells to the combination of radiation plus cigarette smoke condensate generated a neoplastic phenotype. The transformed phenotype promoted increased mammosphere numbers, altered cell cycle phases with a doubling of the population in S phase, and increased invasion and motility. Also, exclusion of Hoechst 33342 dye, a surrogate marker for increased ABC transporters, was observed, which indicates a possible increase in drug resistance. In addition, changes in gene expression include the up regulation of genes encoding proteins involved in metabolic pathways and inflammation. Conclusions The results indicate that when normal breast cells are exposed to low dose

  9. The transcription factor REST is lost in aggressive breast cancer.

    Directory of Open Access Journals (Sweden)

    Matthew P Wagoner

    2010-06-01

    Full Text Available The function of the tumor suppressor RE1 silencing transcription factor (REST is lost in colon and small cell lung cancers and is known to induce anchorage-independent growth in human mammary epithelial cells. However, nothing is currently known about the role of this tumor suppressor in breast cancer. Here, we test the hypothesis that loss of REST function plays a role in breast cancer. To assay breast tumors for REST function, we developed a 24-gene signature composed of direct targets of the transcriptional repressor. Using the 24- gene signature, we identified a previously undefined RESTless breast tumor subtype. Using gene set enrichment analysis, we confirmed the aberrant expression of REST target genes in the REST-less tumors, including neuronal gene targets of REST that are normally not expressed outside the nervous system. Examination of REST mRNA identified a truncated splice variant of REST present in the REST-less tumor population, but not other tumors. Histological analysis of 182 outcome-associated breast tumor tissues also identified a subpopulation of tumors that lack full-length, functional REST and over-express the neuroendocrine marker and REST target gene Chromogranin A. Importantly, patients whose tumors were found to be REST-less using either the 24-gene signature or histology had significantly poorer prognosis and were more than twice as likely to undergo disease recurrence within the first 3 years after diagnosis. We show here that REST function is lost in breast cancer, at least in part via an alternative splicing mechanism. Patients with REST-less breast cancer undergo significantly more early disease recurrence than those with fully functional REST, regardless of estrogen receptor or HER2 status. Importantly, REST status may serve as a predictor of poor prognosis, helping to untangle the heterogeneity inherent in disease course and response to treatment. Additionally, the alternative splicing observed in REST

  10. Zinc isotopic compositions of breast cancer tissue.

    Science.gov (United States)

    Larner, Fiona; Woodley, Laura N; Shousha, Sami; Moyes, Ashley; Humphreys-Williams, Emma; Strekopytov, Stanislav; Halliday, Alex N; Rehkämper, Mark; Coombes, R Charles

    2015-01-01

    An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn isotopic lightness in tumours suggests that sulphur rich metallothionein dominates the isotopic selectivity of a breast tissue cell, rather than Zn-specific proteins. This reveals a possible mechanism of Zn delivery to Zn-sequestering vesicles by metallothionein, and is supported by a similar signature observed in the copper isotopic compositions of one breast cancer patient. This change in intrinsic isotopic compositions due to cancer has the potential to provide a novel early biomarker for breast cancer.

  11. FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

    Science.gov (United States)

    2016-06-02

    Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; 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

  12. Death certification in cancer of the breast.

    OpenAIRE

    1984-01-01

    The cause of death entered on the death certificates of 193 patients originally diagnosed as having cancer of the breast was compared with information obtained from clinical records, cancer registry records, and necropsy findings to determine the accuracy of death certification and the proportion of patients who, though dying from another cause, still had overt signs of cancer of the breast. It was found that the overall error in certifying cause of death as breast cancer was small, being an ...

  13. 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.

  14. The mammary cellular hierarchy and breast cancer.

    Science.gov (United States)

    Oakes, Samantha R; Gallego-Ortega, David; Ormandy, Christopher J

    2014-11-01

    Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.

  15. Coping with a Breast Cancer Diagnosis

    Science.gov (United States)

    ... cancer.org Handling treatment The goal of any breast cancer treatment is to get rid of the cancer and offer the best possible chance of survival. But even the best treatments have side effects. ...

  16. Environmental Factors and Breast Cancer Risk

    Science.gov (United States)

    ... at Stony Brook University found no association between exposure to electromagnetic fields from residential power use and breast cancer risk. 5 National Institute of Environmental Health Sciences Cancer-causing ... to naturally occurring and synthetic cancer, and designing ...

  17. Expression and function of the protein tyrosine phosphatase receptor J (PTPRJ) in normal mammary epithelial cells and breast tumors.

    Science.gov (United States)

    Smart, Chanel E; Askarian Amiri, Marjan E; Wronski, Ania; Dinger, Marcel E; Crawford, Joanna; Ovchinnikov, Dmitry A; Vargas, Ana Cristina; Reid, Lynne; Simpson, Peter T; Song, Sarah; Wiesner, Christiane; French, Juliet D; Dave, Richa K; da Silva, Leonard; Purdon, Amy; Andrew, Megan; Mattick, John S; Lakhani, Sunil R; Brown, Melissa A; Kellie, Stuart

    2012-01-01

    The protein tyrosine phosphatase receptor J, PTPRJ, is a tumor suppressor gene that has been implicated in a range of cancers, including breast cancer, yet little is known about its role in normal breast physiology or in mammary gland tumorigenesis. In this paper we show that PTPRJ mRNA is expressed in normal breast tissue and reduced in corresponding tumors. Meta-analysis revealed that the gene encoding PTPRJ is frequently lost in breast tumors and that low expression of the transcript associated with poorer overall survival at 20 years. Immunohistochemistry of PTPRJ protein in normal human breast tissue revealed a distinctive apical localisation in the luminal cells of alveoli and ducts. Qualitative analysis of a cohort of invasive ductal carcinomas revealed retention of normal apical PTPRJ localization where tubule formation was maintained but that tumors mostly exhibited diffuse cytoplasmic staining, indicating that dysregulation of localisation associated with loss of tissue architecture in tumorigenesis. The murine ortholog, Ptprj, exhibited a similar localisation in normal mammary gland, and was differentially regulated throughout lactational development, and in an in vitro model of mammary epithelial differentiation. Furthermore, ectopic expression of human PTPRJ in HC11 murine mammary epithelial cells inhibited dome formation. These data indicate that PTPRJ may regulate differentiation of normal mammary epithelia and that dysregulation of protein localisation may be associated with tumorigenesis.

  18. Dietary fat and risk of breast cancer

    Directory of Open Access Journals (Sweden)

    Mathew Aleyamma

    2005-07-01

    Full Text Available Abstract Background Breast cancer is one of the major public health problems among women worldwide. A number of epidemiological studies have been carried out to find the role of dietary fat and the risk of breast cancer. The main objective of the present communication is to summarize the evidence from various case-control and cohort studies on the consumption of fat and its subtypes and their effect on the development of breast cancer. Methods A Pubmed search for literature on the consumption of dietary fat and risk of breast cancer published from January 1990 through December 2003 was carried out. Results Increased consumption of total fat and saturated fat were found to be positively associated with the development of breast cancer. Even though an equivocal association was observed for the consumption of total monounsaturated fatty acids (MUFA and the risk of breast cancer, there exists an inverse association in the case of oleic acid, the most abundant MUFA. A moderate inverse association between consumption of n-3 fatty acids and breast cancer risk and a moderate positive association between n-6 fatty acids and breast cancer risk were observed. Conclusion Even though all epidemiological studies do not provide a strong positive association between the consumption of certain types of dietary fat and breast cancer risk, at least a moderate association does seem to exist and this has a number of implications in view of the fact that breast cancer is an increasing public health concern.

  19. Breast-feeding after breast cancer: if you wish, madam.

    Science.gov (United States)

    Azim, Hatem A; Bellettini, Giulia; Gelber, Shari; Peccatori, Fedro A

    2009-03-01

    Breast cancer is the most common malignant tumor-affecting women during the child bearing period. With the rising trend in delaying pregnancy later in life, the issue of subsequent pregnancy and lactation following breast cancer diagnosis has been more frequently encountered. In this context, data is scarce particularly those addressing the issue of lactation. In this review, we discussed different endocrinal, clinical and biological aspects dealing with breast-feeding after breast cancer in an attempt to determine how safe and feasible this approach is.

  20. Education and Outreach for Breast Imaging and Breast Cancer Patients

    Science.gov (United States)

    2003-07-01

    the project was the development of an educational intervention ( flip chart ) for physicians to use in the clinic setting when discussing breast...Procedure Scheduling on Breast Biopsy Patient Outcomes The first phase of this project is the development of an educational flip chart for...breast biopsy and breast cancer survivors to guide the content of the flip chart b) Develop outline and overall format c) Identify/develop

  1. Breast Cancer Risk in American Women

    Science.gov (United States)

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... carry these changes. Mammographic breast density : The glandular (milk-producing) and connective tissue of the breast are ...

  2. Drug transporters in breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Stenvang, Jan; Moreira, José

    2015-01-01

    Despite the advances that have taken place in the past decade, including the development of novel molecular targeted agents, cytotoxic chemotherapy remains the mainstay of cancer treatment. In breast cancer, anthracyclines and taxanes are the two main chemotherapeutic options used on a routine...... basis. Although effective, their usefulness is limited by the inevitable development of resistance, a lack of response to drug-induced cancer cell death. A large body of research has resulted in the characterization of a plethora of mechanisms involved in resistance; ATP-binding cassette transporter...

  3. Breast and Gynecologic Cancer | Division of Cancer Prevention

    Science.gov (United States)

    [[{"fid":"184","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Breast and Gynecologic Cancer Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Breast and Gynecologic Cancer Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Breast and Gynecologic Cancer Research Group Homepage Logo","title":"Breast and Gynecologic Cancer Research Group Homepage Logo","height":"266","width":"400"," | Prevention and early detection of breast, cervix, endometrial and ovarian cancers and their precursors.

  4. Environmental cadmium and breast cancer risk

    OpenAIRE

    2010-01-01

    Breast cancer is the most prevalent women's cancer, with an age-adjusted incidence of 122.9 per 100,000 US women. Cadmium, a ubiquitous carcinogenic pollutant with multiple biological effects, has been reported to be associated with breast cancer in one US regional case-control study. We examined the association of breast cancer with urinary cadmium (UCd), in a case-control sample of women living on Long Island (LI), NY (100 with breast cancer and 98 without), a region with an especially high...

  5. Engineering targeted chromosomal amplifications in human breast epithelial cells.

    Science.gov (United States)

    Springer, Simeon; Yi, Kyung H; Park, Jeenah; Rajpurohit, Anandita; Price, Amanda J; Lauring, Josh

    2015-07-01

    Chromosomal amplifications are among the most common genetic alterations found in human cancers. However, experimental systems to study the processes that lead to specific, recurrent amplification events in human cancers are lacking. Moreover, some common amplifications, such as that at 8p11-12 in breast cancer, harbor multiple driver oncogenes, which are poorly modeled by conventional overexpression approaches. We sought to develop an experimental system to model recurrent chromosomal amplification events in human cell lines. Our strategy is to use homologous-recombination-mediated gene targeting to deliver a dominantly selectable, amplifiable marker to a specified chromosomal location. We used adeno-associated virus vectors to target human MCF-7 breast cancer cells at the ZNF703 locus, in the recurrent 8p11-12 amplicon, using the E. coli inosine monophosphate dehydrogenase (IMPDH) enzyme as a marker. We applied selective pressure using IMPDH inhibitors. Surviving clones were found to have increased copy number of ZNF703 (average 2.5-fold increase) by droplet digital PCR and FISH. Genome-wide array comparative genomic hybridization confirmed that amplifications had occurred on the short arm of chromosome 8, without changes on 8q or other chromosomes. Patterns of amplification were variable and similar to those seen in primary human breast cancers, including "sawtooth" patterns, distal copy number loss, and large continuous regions of copy number gain. This system will allow study of the cis- and trans-acting factors that are permissive for chromosomal amplification and provide a model to analyze oncogene cooperativity in amplifications harboring multiple candidate driver genes.

  6. Breast Cancer Translational Research Center of Excellence

    Science.gov (United States)

    2015-09-01

    the standard of care for treating breast diseases and breast cancer. This approach integrates prevention , screening, diagnosis, treatment and...follow a healthy lifestyle ?” (submitted for publication clearance April 2015). Ellsworth RE, Mamula KA, Costantino NS, Deyarmin B, Kostyniak PJ, Chi...disorders. The project will continue utilizing a multidisciplinary approach as the standard of care for treating breast diseases and breast cancer. This

  7. Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy.

    Science.gov (United States)

    Bai, Huimin; Cao, Dongyan; Yang, Jiaxin; Li, Menghui; Zhang, Zhenyu; Shen, Keng

    2016-04-01

    Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular-targeted therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)-related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival.

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

    Science.gov (United States)

    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.

  9. Repression of mammosphere formation in breast cancer cells by soy isoflavone genistein and blueberry polyphenols

    Science.gov (United States)

    Epidemiological evidence implicates diets rich in fruits and vegetables in breast cancer prevention due to their phytochemical components, yet mechanisms for their anti-tumor activities are not well-understood. A small population of mammary epithelial cells, termed cancer stem cells (CSC), may be re...

  10. THE MAMMOGRAPHIC CALCIFICATIONS IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    Tang Ruiying; Liu Jingxian; Gaowen

    1998-01-01

    Objective: This study was performed to exam the relativeship between mammographic calcifications and breast cancer. Methods: All of the 184 patients with breast diseases underwent mammography before either an open biopsy or a mastectomy. The presence,morphology, and distribution of calcifications visualized on mammograms for breast cancer were compared with the controls who remained cancer free. Statistical comparisons were made by using the x2 test. Results:Of the 184 patients with breast diaeases, 93 malignant and 91 benign lesions were histologically confirmed.Calcifications were visualized on mammograms in 60(64%) of 93 breast cancers and 26 (28%) of 91 non breast cancers. The estimated odds ratio (OR) of breast cancer was 4.5 in women with calcifications seen on mammograms, compared with those having none (P<0.01). Of the 60 breast carcinomas having mammographic calcifications, 28 (47%) were infiltrating ductal carcinomas.There were only 8 (24%) cases with infiltrating ductal cancers in the group of without calcifications seen on the mammograms (P<0.05). Conclusion: Our finding suggests that mammographic calcification appears to be a risk factor for breast cancer. The granular and linear cast type calcification provide clues to the presence of breast cancer, especially when the carcinomas without associated masses were seen on mammograms.

  11. Knowing Their Breast Cancer Risk May Empower Teens

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_161233.html Knowing Their Breast Cancer Risk May Empower Teens Greater self-esteem noted in ... interviewed to assess their mental health, perception of breast cancer risk, and levels of distress about breast cancer. The ...

  12. NIH study confirms risk factors for male breast cancer

    Science.gov (United States)

    Pooled data from studies of about 2,400 men with breast cancer and 52,000 men without breast cancer confirmed that risk factors for male breast cancer include obesity, a rare genetic condition called Klinefelter syndrome, and gynecomastia.

  13. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

    DEFF Research Database (Denmark)

    Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P.

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants co...

  14. The identification and characterization of breast cancer CTCs competent for brain metastasis

    OpenAIRE

    2013-01-01

    Brain metastatic breast cancer (BMBC) is uniformly fatal and increasing in frequency. Despite its devastating outcome, mechanisms causing BMBC remain largely unknown. The mechanisms that implicate circulating tumor cells (CTCs) in metastatic disease, notably in BMBC, remain elusive. Here we characterize CTCs isolated from peripheral blood mononuclear cells (PBMCs) of patients with breast cancer, and also develop CTC lines from three of these patients. In epithelial cell adhesion molecule (EpC...

  15. 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

  16. Propranolol and survival from breast cancer

    DEFF Research Database (Denmark)

    Cardwell, Chris R; Pottegård, Anton; Vaes, Evelien;

    2016-01-01

    BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all......-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all......-cause mortality were available for five and eight cohorts, respectively. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality by propranolol and non-selective beta-blocker use. HRs were pooled across cohorts using meta...

  17. Characterization of a naturally occurring breast cancer subset enriched in EMT and stem cell characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Hennessy, Bryan T.; Gonzalez-Angulo, Ana-Maria; Stemke-Hale, Katherine; Gilcrease, Michael Z.; Krishnamurthy, Savitri; Lee, Ju-Seog; Fridlyand, Jane; Sahin, Aysegul; Agarwal, Roshan; Joy, Corwin; Liu, Wenbin; Stivers, David; Baggerly, Keith; Carey, Mark; Lluch, Ana; Monteagudo, Carlos; He, Xiaping; Weigman, Victor; Fan, Cheng; Palazzo, Juan; Hortobagyi, Gabriel N.; Nolden, Laura K.; Wang, Nicholas J.; Valero, Vicente; Gray, Joe W.; Perou, Charles M.; Mills, Gordon B.

    2009-05-19

    Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor-positive cancers (34.5%; P = 0.32), 17 of 75 HER-2-positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P < 0.0001), and 0 of 14 claudin-low tumors (P = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a 'tumorigenic' signature defined using CD44{sup +}/CD24{sup -} breast tumor-initiating stem cell-like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell-like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. PIK3CA mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets.

  18. Educational Counseling in Improving Communication and Quality of Life in Spouses and Breast Cancer Patients

    Science.gov (United States)

    2014-12-29

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Psychosocial Effects of Cancer and Its Treatment; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  19. Environmental cadmium and breast cancer risk.

    Science.gov (United States)

    Gallagher, Carolyn M; Chen, John J; Kovach, John S

    2010-11-01

    Breast cancer is the most prevalent women's cancer, with an age-adjusted incidence of 122.9 per 100,000 US women. Cadmium, a ubiquitous carcinogenic pollutant with multiple biological effects, has been reported to be associated with breast cancer in one US regional case-control study. We examined the association of breast cancer with urinary cadmium (UCd), in a case-control sample of women living on Long Island (LI), NY (100 with breast cancer and 98 without), a region with an especially high rate of breast cancer (142.7 per 100,000 in Suffolk County) and in a representative sample of US women (NHANES 1999-2008, 92 with breast cancer and 2,884 without). In a multivariable logistic model, both samples showed a significant trend for increased odds of breast cancer across increasing UCd quartiles (NHANES, p=0.039 and LI, p=0.023). Compared to those in the lowest quartile, LI women in the highest quartile had increased risk for breast cancer (OR=2.69; 95% CI=1.07, 6.78) and US women in the two highest quartiles had increased risk (OR=2.50; 95% CI=1.11, 5.63 and OR=2.22; 95% CI=.89, 5.52, respectively). Further research is warranted on the impact of environmental cadmium on breast cancer risk in specific populations and on identifying the underlying molecular mechanisms.

  20. Analysis of differential protein expression in normal and neoplastic human breast epithelial cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Williams, K.; Chubb, C.; Huberman, E.; Giometti, C.S.

    1997-07-01

    High resolution two dimensional get electrophoresis (2DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent of the consistently detected proteins were found in significantly (P < 0.001) variable levels among the cell lines. Using a combination of immunostaining, comigration with purified protein, subcellular fractionation, and amino-terminal protein sequencing, we identified a subset of the differentially expressed proteins. These identified proteins include the cytoskeletal proteins actin, tubulin, vimentin, and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27, hsp60, and hsp70 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Finally, we identified IMP dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells.

  1. Id-1 gene and gene products as therapeutic targets for treatment of breast cancer and other types of carcinoma

    Science.gov (United States)

    Desprez, Pierre-Yves; Campisi, Judith

    2014-08-19

    A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.

  2. Typhoid Vaccine in Testing Response to Immune Stress in Patients With Stage I-IIIA Breast Cancer Who Received Chemotherapy

    Science.gov (United States)

    2016-11-29

    Cognitive Side Effects of Cancer Therapy; Depression; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  3. Microarray expression analysis of epithelial ovarian cancer with distinct differentiation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To identify gene expression profiling in epithelial ovarian cancer and to explore its correlation with histopathology characterization and prognosis. Gene expression profiles were generated from 10 human ovarian frozen tissue specimens using Agilent Human 1A microarrays. Strikingly, clear differences of gene expression patterns were observed in ovarian cancer as compared to normal tissues. Unique gene profiles were observed in moderately and poorly differentiated epithelial ovarian cancer. It is concluded that different histopathology characterization likely exists extensive molecular heterogeneity.

  4. [CHEK2-mutation in Dutch breast cancer families: expanding genetic testing for breast cancer

    NARCIS (Netherlands)

    Adank, M.A.; Hes, F.J.; Zelst-Stams, W.A.G. van; Tol, M.P. van den; Seynaeve, C.; Oosterwijk, J.C.

    2015-01-01

    - In the majority of breast cancer families, DNA testing does not show BRCA1 or BRCA2 mutations and the genetic cause of breast cancer remains unexplained. - Routine testing for the CHEK2*1100delC mutation has recently been introduced in breast cancer families in the Netherlands. - The 1100delC muta

  5. Breast cancer heterogeneity: mechanisms, proofs, and implications

    Directory of Open Access Journals (Sweden)

    Yi-Hsuan Hsiao, Ming-Chih Chou, Carol Fowler, Jeffrey T. Mason, Yan-gao Man

    2010-01-01

    Full Text Available Human breast cancer represents a group of highly heterogeneous lesions consisting of about 20 morphologically distinct subtypes with substantially different molecular and/or biochemical signatures, clinical courses, and prognoses. This study analyzed the possible correlation between the morphological presentations of breast cancer and two hypothesized models of carcinogenesis, in order to identify the intrinsic mechanism(s and clinical implications of breast cancer heterogeneity.

  6. The p53 pathway in breast cancer

    OpenAIRE

    Gasco, Milena; Shami, Shukri; Crook, Tim

    2002-01-01

    p53 mutation remains the most common genetic change identified in human neoplasia. In breast cancer, p53 mutation is associated with more aggressive disease and worse overall survival. The frequency of mutation in p53 is, however, lower in breast cancer than in other solid tumours. Changes, both genetic and epigenetic, have been identified in regulators of p53 activity and in some downstream transcriptional targets of p53 in breast cancers that express wild-type p53. Molecular pathological an...

  7. Breast Cancer: Catch It with Ultrasound

    Science.gov (United States)

    2011-09-01

    Heintz, Ph.D. Department of Radiology, University of New Mexico School of Medicine, Albuquerque, NM e-mail: MWilliamson@salud.unm.edu Breast cancer ...AD_________________ Award Number: W81XWH-10-1-0566 TITLE: Breast Cancer : Catch It with Ultrasound...CONTRACT NUMBER Breast Cancer : Catch It with Ultrasound 5b. GRANT NUMBER W81XWH-10-1-0566 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT

  8. Targeting ESR1-Mutant Breast Cancer

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1-Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1-Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT...mutations found in breast cancer using both structural and cell based assays. We have now have evidence for the effects of the most recurrent

  9. Knowledge towards breast cancer among Libyan women in Tripoli

    Directory of Open Access Journals (Sweden)

    Yousef A Taher

    2016-11-01

    Conclusion: Our findings demonstrate that Libyan women have acceptable level of knowledge regarding breast cancer. However, improvement of the health systems and awareness regarding breast cancer is needed.

  10. 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.

  11. Diazepam use and progression of breast cancer.

    Science.gov (United States)

    Kleinerman, R A; Brinton, L A; Hoover, R; Fraumeni, J F

    1984-03-01

    The relationship between diazepam and breast cancer was evaluated using data from a case-control study of breast cancer, in which 1075 cases and 1146 controls who were participants in a breast cancer screening program were interviewed. Diazepam use was negatively associated with extent of disease and lymph node involvement, and this effect seemed greatest for long-term users of diazepam. It is not certain to what extent these data reflect an ascertainment bias, an association with the reasons for which the drug was prescribed, or chance. Whatever the explanation, the findings do not support a previous contention that diazepam promotes or accelerates breast cancer growth.

  12. Breast Cancer Screening and Prevention.

    Science.gov (United States)

    Nattinger, Ann B; Mitchell, Julie L

    2016-06-07

    This issue provides a clinical overview of breast cancer screening and prevention, focusing on risk assessment, screening, prevention, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  13. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2015-09-01

    myocardial infarction among apparently healthy men. Circulation 101, 1767 (Apr 18, 2000). 33. E. A. Rakha, Pitfalls in outcome prediction of breast...cancer patients at diagnosis IL-6 plasma levels have been shown to be elevated in advanced metastatic BC patients (15, 31). To investigate whether the...plasma from BC patients was collected at diagnosis prior to surgery or any therapy. Interestingly, we found that IL-6 plasma levels were not

  14. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2014-09-01

    be cultured in calcium‐ free DMEM supplemented with 1% FBS, cholera toxin (10 ng/ml), bovine insulin (3 μg/ml), hydrocortisone (0.5 μg/ml), EGF and...regimens for induction of optimal anti-tumor immunity. Then we will determine the optimal time to administer these regimens during disease ...node status. Breast Cancer Res Treat 60, 227 (Apr, 2000). 4. H. E. Kohrt et al., Profile of immune cells in axillary lymph nodes predicts disease -free

  15. Cell volume regulation in epithelial physiology and cancer

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Hoffmann, Else Kay; Novak, Ivana

    2013-01-01

    The physiological function of epithelia is transport of ions, nutrients, and fluid either in secretory or absorptive direction. All of these processes are closely related to cell volume changes, which are thus an integrated part of epithelial function. Transepithelial transport and cell volume...... expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion...... transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed....

  16. Breast cancer management: Past, present and evolving

    Directory of Open Access Journals (Sweden)

    M Akram

    2012-01-01

    Full Text Available Breast cancer is known from ancient time,and the treatment strategy evolved as our understanding of the disease changed with time. In 460 BC Hippocrates described breast cancer as a humoral disease and presently after a lot of studies breast cancer is considered as a local disease with systemic roots. For most of the twentieth century Halsted radical mastectomy was the "established and standardized operation for cancer of the breast in all stages, early or late". New information about tumor biology and its behavior suggested that less radical surgery might be just as effective as the more extensive one. Eventually, with the use of adjuvant therapy likeradiation and systemic therapy, the extent of surgical resection in the breast and axilla got reduced further and led to an era of breast conservation. The radiation treatment of breast cancer has evolved from 2D to 3D Conformal and to accelarated partial breast irradiation, aiming to reduce normal tissue toxicity and overall treatment time. Systemic therapy in the form of hormone therapy, chemotherapy and biological agents is now a well-established modality in treatment of breast cancer. The current perspective of breast cancer management is based on the rapidly evolving and increasingly integrated study on the genetic, molecular , biochemical and cellular basis of disease. The challenge for the future is to take advantage of this knowledge for the prediction of therapeutic outcome and develop therapies and rapidly apply more novel biologic therapeutics.

  17. Accessory breast tissue in axilla masquerading as breast cancer recurrence

    Directory of Open Access Journals (Sweden)

    Goyal Shikha

    2008-01-01

    Full Text Available Ectopic or accessory breast tissue is most commonly located in the axilla, though it may be present anywhere along the milk line. Development is hormone dependent, similar to normal breast tissue. These lesions do not warrant any intervention unless they produce discomfort, thus their identification and distinction from other breast pathologies, both benign and malignant, is essential. We report a case with locally advanced breast cancer who presented with an ipsilateral axillary mass following surgery, radiotherapy, and chemotherapy. Subsequent evaluation with excision biopsy showed duct ectasia in axillary breast tissue and the patient was continued on hormone therapy with tamoxifen.

  18. Breast Cancer 2012 - New Aspects.

    Science.gov (United States)

    Kolberg, H-C; Lüftner, D; Lux, M P; Maass, N; Schütz, F; Fasching, P A; Fehm, T; Janni, W; Kümmel, S

    2012-07-01

    Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, however potentially promising combinations do not always achieve a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also inherited genetic properties of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Also health-economic aspects are more frequently being taken into consideration so that health-economic considerations may also play a part. This review is based on information from the recent annual congresses. The latest of these are the 34th San Antonio Breast Cancer Symposium 2011 and the ASCO Annual Meeting 2012. Among their highlights are the clinically significant results from the CLEOPATRA, BOLERO-2, EMILIA and SWOG S0226 trials on the therapy for metastatic breast cancer as well as further state-of-the-art data on the adjuvant use of bisphosphonates within the framework of the ABCSG-12, ZO-FAST, NSABP-B34 and GAIN trials.

  19. Pregnancy-induced changes in breast cancer risk.

    Science.gov (United States)

    Russo, Irma H; Russo, Jose

    2011-09-01

    Breast cancer is the malignant disease most frequently diagnosed in women of all races and nationalities. Since the 1970s the worldwide incidence of this disease has increased 30-40% in postmenopausal women, in whom, paradoxically, the risk of developing breast cancer is significantly reduced by an early first full term pregnancy (FTP) as compared to nulliparous and late parous women. Although the cause of breast cancer is not known, the mechanisms mediating the protection conferred by an early FTP have been identified to reside in the breast itself, and to be modulated by endogenous and environmental exposures that might negatively affect this organ during specific windows in its development that extend from prenatal life until the first pregnancy. Soon after conception the embryo initiates the production of human chorionic gonadotropin (hCG), the glycoprotein hormone that is diagnostic of pregnancy. HCG in conjunction with ovarian steroid hormones primes the hypothalamic neuroendocrine system for maintaining the pregnancy. Higher levels of hCG during the first trimester of pregnancy have been associated with a reduction in maternal breast cancer incidence after age 50. In preclinical studies it has been demonstrated that both FTP and hCG treatment of virgin rats prevent the development of chemically-induced mammary tumors, a phenomenon mediated by the differentiation of the mammary gland epithelial cells prior to carcinogen exposure. Complete differentiation proceeds through complex morphological, physiological and molecular changes that occur during pregnancy and lactation, that ultimately result in increased DNA repair capabilities of the mammary epithelium, activation of genes controlling differentiation and programmed cell death and imprinting in the breast epithelium a specific and permanent genomic signature of pregnancy. This signature is indicative of a reduced breast cancer risk and serves as a molecular biomarker of differentiation for evaluating the

  20. How pregnancy at early age protects against breast cancer.

    Science.gov (United States)

    Meier-Abt, Fabienne; Bentires-Alj, Mohamed

    2014-03-01

    Pregnancy at an early age has a strong protective effect against breast cancer in humans and rodents. Postulated mechanisms underlying this phenomenon include alterations in the relative dynamics of hormone and growth factor-initiated cell fate-determining signaling pathways within the hierarchically organized mammary gland epithelium. Recent studies in epithelial cell subpopulations isolated from mouse and human mammary glands have shown that early pregnancy decreases the proportion of hormone receptor-positive cells and causes pronounced changes in gene expression as well as decreased proliferation in stem/progenitor cells. The changes include downregulation of Wnt and transforming growth factor β (TGFβ) signaling. These new findings highlight the importance of cell-cell interactions within the mammary gland epithelium in modulating cancer risk and provide potential targets for breast cancer prevention strategies.

  1. [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.

  2. Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

    Science.gov (United States)

    Singer, Adam; Tresley, Jonathan; Velazquez-Vega, Jose; Yepes, Monica

    2013-02-01

    For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

  3. Association between breast and thyroid cancers

    Directory of Open Access Journals (Sweden)

    Lehrer S

    2014-02-01

    Full Text Available Steven Lehrer, Sheryl Green, John A Martignetti, Kenneth E Rosenzweig Departments of Radiation Oncology and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: The risk of thyroid cancer is known to be slightly increased in women after treatment for breast cancer. In the current study, we analyzed the incidence of thyroid cancer and breast cancer in 50 US states and in the District of Columbia to ascertain how often these two diseases are associated. Methods: Data on the incidence of thyroid cancer were obtained from the Centers for Disease Control and Prevention and the National Cancer Institute and data on the incidence of breast cancer were from the American Cancer Society. Data on the average number of children per family with children and mean household income were sourced from the US Bureau of the Census and prevalence of obesity by state is determined from a paper published in 2010 on state-specific obesity prevalence among US adults by the Centers for Disease Control and Prevention. Results: There was a significant association between breast and thyroid cancer (P=0.002. Since the incidence of breast cancer increases with increasing income and obesity, while decreasing with parity, multiple linear regression was performed. Breast cancer incidence was significantly related to thyroid cancer incidence (β=0.271, P=0.039, inversely related to average number of children per family with children (β=-0.271, P=0.039, unrelated to adult obesity (β=0.134, P=0.369, and significantly related to family income (β=0.642, P<0.001. Conclusion: This study identifies an association between breast and thyroid cancer. The association suggests that unexplored breast-thyroid cancer susceptibility loci exist and warrant further study. Keywords: breast cancer, thyroid cancer, genetics, association

  4. Long-term side effects of adjuvant breast cancer treatment

    NARCIS (Netherlands)

    Buijs, Ciska

    2008-01-01

    Breast cancer is the most common malignancy in women. Breast cancer accounts for one-third of all cancers in females and 24% of the patients are younger than 55 years of age. More than 10% all Dutch women will develop breast cancer and 70-80% of all breast cancer patients will survive over 5 years.

  5. The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

    DEFF Research Database (Denmark)

    Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn;

    2001-01-01

    The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neopl......The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated...... that neoplastic breast epithelial cells may be substantially more plastic in their differentiation repertoire than previously anticipated. Thus, along with an increasing availability of markers for the myoepithelial lineage, at least a partial differentiation towards this lineage is being revealed frequently....... It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells...

  6. Mutagens in human breast lipid and milk: the search for environmental agents that initiate breast cancer.

    Science.gov (United States)

    Phillips, David H; Martin, Francis L; Williams, J Andrew; Wheat, Luise M C; Nolan, Lisa; Cole, Kathleen J; Grover, Philip L

    2002-01-01

    Epidemiological studies indicate the involvement of environmental factors in the etiology of breast cancer, but have not provided clear indications of the nature of the agents responsible. Several environmental carcinogens are known to induce mammary tumors in rodents, and the abundance of adipose tissue in the human breast suggests that the epithelial cells, from which breast tumors commonly arise, could be exposed to lipid-soluble carcinogens sequestered by the adipose tissue. In this report we review our studies in which we have examined human mammary lipid, obtained from elective reduction mammoplasties from healthy donors, and human milk from healthy mothers, for the presence of components with genotoxic activity in several in vitro assays. A significant proportion of lipid extracts induced mutations in bacteria and micronuclei in mammalian cells. They also caused DNA damage, detected as single-strand breaks in the alkaline single-cell gel electrophoresis (comet) assay, in both the MCL-5 cell line and in primary cultures of human mammary epithelial cells. Genotoxic activity was also found in a significant proportion of extracts of human breast milk. Viable cells recovered from milk samples showed evidence of DNA damage and were susceptible to comet formation by genotoxic agents in vitro. Genotoxic activity was found to be less prevalent in milk samples from countries of lower breast cancer incidence (the Far East) compared with that in samples from the UK. The agents responsible for the activity in milk appear to be moderately polar lipophilic compounds and of low molecular weight. Identification of these agents and their sources may hold clues to the origins of breast cancer.

  7. Stages of Breast Cancer

    Science.gov (United States)

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... in dozens of tiny bulbs that can make milk. The lobes, lobules, and bulbs are linked by ...

  8. Identification of H-Ras-Specific Motif for the Activation of Invasive Signaling Program in Human Breast Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Hae-Young Yong

    2011-02-01

    Full Text Available Increased expression and/or activation of H-Ras are often associated with tumor aggressiveness in breast cancer. Previously, we showed that H-Ras, but not N-Ras, induces MCF10A human breast epithelial cell invasion and migration, whereas both H-Ras and N-Ras induce cell proliferation and phenotypic transformation. In an attempt to determine the sequence requirement directing the divergent phenotype induced by H-Ras and N-Ras with a focus on the induction of human breast cell invasion, we investigated the structural and functional relationships between H-Ras and N-Ras using domain-swap and site-directed mutagenesis approaches. Here, we report that the hypervariable region (HVR, consisting of amino acids 166 to 189 in H-Ras, determines the invasive/migratory signaling program as shown by the exchange of invasive phenotype by swapping HVR sequences between H-Ras and N-Ras. We also demonstrate that the H-Ras-specific additional palmitoylation site at Cys184 is not responsible for the signaling events that distinguish between H-Ras and N-Ras. Importantly, this work identifies the C-terminal HVR, especially the flexible linker domain with two consecutive proline residues Pro173 and Pro174, as a critical domain that contributes to activation of H-Ras and its invasive potential in human breast epithelial cells. The present study sheds light on the structural basis for the Ras isoform-specific invasive program of breast epithelial cells, providing information for the development of agents that specifically target invasion-related H-Ras pathways in human cancer.

  9. Autophagy regulates keratin 8 homeostasis in mammary epithelial cells and in breast tumors

    Science.gov (United States)

    Kongara, Sameera; Kravchuk, Olga; Teplova, Irina; Lozy, Fred; Schulte, Jennifer; Moore, Dirk; Barnard, Nicola; Neumann, Carola A.; White, Eileen; Karantza, Vassiliki

    2010-01-01

    Autophagy is activated in response to cellular stressors and mediates lysosomal degradation and recycling of cytoplasmic material and organelles as a temporary cell survival mechanism. Defective autophagy is implicated in human pathology, as disruption of protein and organelle homeostasis enables disease-promoting mechanisms such as toxic protein aggregation, oxidative stress, genomic damage and inflammation. We previously showed that autophagy-defective immortalized mouse mammary epithelial cells (iMMECs) are susceptible to metabolic stress, DNA damage and genomic instability. We now report that autophagy deficiency was associated with ER and oxidative stress, and deregulation of p62-mediated keratin homeostasis in mammary cells and allograft tumors and in mammary tissues from genetically engineered mice. In human breast tumors, high phospho(Ser73)-K8 levels inversely correlated with Beclin 1 expression. Thus, autophagy preserves cellular fitness by limiting ER and oxidative stress, a function potentially important in autophagy-mediated suppression of mammary tumorigenesis. Furthermore, autophagy regulates keratin homeostasis in the mammary gland via a p62-dependent mechanism. High phospho(Ser73)-K8 expression may be a marker of autophagy functional status in breast tumors and, as such, could have therapeutic implications for breast cancer patients. PMID:20530580

  10. 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

  11. 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.

  12. Manganese superoxide dismutase and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Christensen, Mariann; Lash, Timothy L

    2014-01-01

    cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses. METHODS: We conducted a population-based case-control study of BCR among women in Jutland, Denmark. Subjects were diagnosed with non......BACKGROUND: Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast......-metastatic breast cancer from 1990-2001, received adjuvant Cyclo, and were registered in the Danish Breast Cancer Cooperative Group. We identified 118 patients with BCR and 213 matched breast cancer controls. We genotyped SOD2 and used conditional logistic regression to compute the odds ratio (OR) and associated 95...

  13. MicroRNA Regulation of Human Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yohei Shimono

    2015-12-01

    Full Text Available MicroRNAs (miRNAs are involved in virtually all biological processes, including stem cell maintenance, differentiation, and development. The dysregulation of miRNAs is associated with many human diseases including cancer. We have identified a set of miRNAs differentially expressed between human breast cancer stem cells (CSCs and non-tumorigenic cancer cells. In addition, these miRNAs are similarly upregulated or downregulated in normal mammary stem/progenitor cells. In this review, we mainly describe the miRNAs that are dysregulated in human breast CSCs directly isolated from clinical specimens. The miRNAs and their clusters, such as the miR-200 clusters, miR-183 cluster, miR-221-222 cluster, let-7, miR-142 and miR-214, target the genes and pathways important for stem cell maintenance, such as the self-renewal gene BMI1, apoptosis, Wnt signaling, Notch signaling, and epithelial-to-mesenchymal transition. In addition, the current evidence shows that metastatic breast CSCs acquire a phenotype that is different from the CSCs in a primary site. Thus, clarifying the miRNA regulation of the metastatic breast CSCs will further advance our understanding of the roles of human breast CSCs in tumor progression.

  14. RAD51B in Familial Breast Cancer

    DEFF Research Database (Denmark)

    Pelttari, Liisa M; Khan, Sofia; Vuorela, Mikko

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition......, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD......51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients...

  15. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  16. Living as a Breast Cancer Survivor

    Science.gov (United States)

    ... cancers after breast cancer . Ask your doctor for a survivorship care plan Talk with your doctor about ... Close Image of Previous Next Close Close Select A Hope Lodge Close Please share your thoughts about ...

  17. Breast Cancers Between Mammograms Have Aggressive Features

    Science.gov (United States)

    Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.

  18. Evolution of surgical treatment for breast cancer

    Directory of Open Access Journals (Sweden)

    V. P. Letyagin

    2012-01-01

    Full Text Available The paper considers main surgical interventions used to treat breast cancer. It defines the role and place of conservative surgery and describes current procedures for the organ-saving treatment of cancer at this site.

  19. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    Science.gov (United States)

    2016-10-04

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  20. Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer.

    Science.gov (United States)

    Robinson, Dan R; Kalyana-Sundaram, Shanker; Wu, Yi-Mi; Shankar, Sunita; Cao, Xuhong; Ateeq, Bushra; Asangani, Irfan A; Iyer, Matthew; Maher, Christopher A; Grasso, Catherine S; Lonigro, Robert J; Quist, Michael; Siddiqui, Javed; Mehra, Rohit; Jing, Xiaojun; Giordano, Thomas J; Sabel, Michael S; Kleer, Celina G; Palanisamy, Nallasivam; Natrajan, Rachael; Lambros, Maryou B; Reis-Filho, Jorge S; Kumar-Sinha, Chandan; Chinnaiyan, Arul M

    2011-11-20

    Breast cancer is a heterogeneous disease that has a wide range of molecular aberrations and clinical outcomes. Here we used paired-end transcriptome sequencing to explore the landscape of gene fusions in a panel of breast cancer cell lines and tissues. We observed that individual breast cancers have a variety of expressed gene fusions. We identified two classes of recurrent gene rearrangements involving genes encoding microtubule-associated serine-threonine kinase (MAST) and members of the Notch family. Both MAST and Notch-family gene fusions have substantial phenotypic effects in breast epithelial cells. Breast cancer cell lines harboring Notch gene rearrangements are uniquely sensitive to inhibition of Notch signaling, and overexpression of MAST1 or MAST2 gene fusions has a proliferative effect both in vitro and in vivo. These findings show that recurrent gene rearrangements have key roles in subsets of carcinomas and suggest that transcriptome sequencing could identify individuals with rare, targetable gene fusions.

  1. Early Life and Risk of Breast Cancer

    Science.gov (United States)

    2004-08-01

    adulthood in the 1958 British born cohort. Am J Clin Nutr 1997; 66:1094-101. 52. Kvale G, Heuch I. Menstrual factors and breast cancer risk. Cancer 1988; 62...Biomarkers Prey 2002;11: J Clin Nutr 1997;66:1094-101. 32. He Q Karlbergj. BMI in childhood and 207-10. 28. Kvale G, Heuch I. Menstrual factors and its...breast cancer among young U.S. women. Epidemiology 1997; 8(5):559-565. (76) Kvale G, Heuch I. Menstrual factors and breast cancer risk. Cancer 1988; 62(8

  2. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk

    DEFF Research Database (Denmark)

    Cannioto, Rikki; LaMonte, Michael J; Risch, Harvey A

    2016-01-01

    BACKGROUND: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC ri...

  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. EpCAM modulates NF-κB signaling and interleukin-8 expression in breast cancer.

    Science.gov (United States)

    Sankpal, Narendra V; Fleming, Timothy P; Gillanders, William E

    2013-04-01

    The epithelial cell adhesion molecule (EpCAM) is a 40-kD type I transmembrane protein that is overexpressed in human epithelial cancers and is currently the target of molecular therapy based on its overexpression at the cell surface. Recently, we and others have shown a role for EpCAM in cell signaling and carcinogenesis, and EpCAM expression seems to promote breast cancer invasion. Interleukin-8 (IL-8/CXCL-8) is an inflammatory cytokine that has recently been shown to modulate breast cancer invasion and angiogenesis. In preliminary experiments, we identified a correlation between EpCAM and IL-8 expression in primary human breast cancers. Specific ablation of EpCAM in breast cancer cell lines results in decreased IL-8 expression, and IL-8 contributes to EpCAM-dependent breast cancer invasion. Specific ablation of EpCAM is also associated with decreased NF-κB transcription factor activity, decreased phosphorylation of the NF-κB family member RELA, and increased IκBα protein expression. EpCAM modulates IL-8 expression at baseline, and following IL-1β stimulation, which is known to be a potent inducer of NF-κB in breast cancer. In functional rescue experiments, specific ablation of RELA or forced expression of the NF-κB inhibitor protein IκBα prevented EpCAM-dependent rescue of IL-8 promoter activity. These studies show for the first time that EpCAM can modulate NF-κB transcription factor activity and IL-8 expression in breast cancer and confirm the role of EpCAM signaling in modulating breast cancer invasion. Further study is required to define the molecular mechanism(s) of EpCAM signaling in breast cancer and to direct the rational development of molecular therapies targeting EpCAM.

  5. Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

    Science.gov (United States)

    2016-10-04

    Estrogen Receptor Negative; HER2 Positive Breast Carcinoma; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer

  6. Breast Cancer During Pregnancy: Case Report

    Directory of Open Access Journals (Sweden)

    Serden Ay

    2013-06-01

    Full Text Available During pregnancy breast cancer is rarely seen. In this case, when the patient was being operated for the right breast cancer which was diagnosed in the first exam, a left breast cancer was also detected in the operation. When the patient analysed retrospectively, lesion in the left breast could not detected because of the lactation period. Consequently,pregnancy patients must be re-examined after the lactation period to avoid any possible mistakes. [Cukurova Med J 2013; 38(3.000: 492-494

  7. Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice.

    Science.gov (United States)

    Wu, Min; Jung, Lina; Cooper, Adrian B; Fleet, Christina; Chen, Lihao; Breault, Lyne; Clark, Kimberly; Cai, Zuhua; Vincent, Sylvie; Bottega, Steve; Shen, Qiong; Richardson, Andrea; Bosenburg, Marcus; Naber, Stephen P; DePinho, Ronald A; Kuperwasser, Charlotte; Robinson, Murray O

    2009-04-28

    Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.

  8. Urinary phytoestrogens and postmenopausal breast cancer risk

    NARCIS (Netherlands)

    Tonkelaar, den I.; Keinan-Boker, L.; Veer, van't P.; Arts, C.J.M.; Adlercreutz, H.; Thijssen, J.H.H.; Peeters, H.M.

    2001-01-01

    Phytoestrogens are defined as plant substances that are structurally or functionally similar to estradiol. We report the associations of two major phytoestrogens, genistein and enterolactone, with breast cancer risk, using urinary specimens collected 1-9 years before breast cancer was diagnosed. The

  9. Screening for breast cancer with mammography

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Jørgensen, Karsten Juhl

    2013-01-01

    A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary.......A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary....

  10. Loneliness May Sabotage Breast Cancer Survival: Study

    Science.gov (United States)

    ... gov/news/fullstory_162498.html Loneliness May Sabotage Breast Cancer Survival: Study Weak social ties linked to higher risk ... 2016 (HealthDay News) -- Loneliness may impede long-term breast cancer survival, a new study suggests. In the years after ...

  11. Gene Expression Analysis of Breast Cancer Progression

    Science.gov (United States)

    2005-07-01

    Giri D, Chen B, Gerald W Molecular Diagnosis of Breast Cancer Therapeutic Biomarkers Using Oligonucleotide Arrays Abstract presentation USCAP 2005. 5...Bone Metastasis. Submitted Lal P, Donaton M, Girl D, Chen B, Gerald W Molecular Diagnosis of Breast Cancer Therapeutic Biomarkers Using Oligonucleotide

  12. Paclitaxel and doxorubicin in metastatic breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T;

    1996-01-01

    be explored. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be highly effective in treating patients with advanced breast cancer, including those with anthracycline-resistant breast cancer, a fact that has led to efforts to combine paclitaxel and anthracyclines...

  13. New ways to optimize breast cancer treatment

    NARCIS (Netherlands)

    Schröder, Carolina Pia

    2001-01-01

    Breast cancer patients without apparent distant metastases at the time of primary tumor removal, may later suffer from a distant relapse, indicating the presence of occult micrometastases at the time of diagnosis. Sensitive methods to detect micrometastatic breast cancer may be helpful in optimizing

  14. Breast cancer radiotherapy and cardiac risk

    OpenAIRE

    Anusheel Munshi; Kaustav Talapatra; Debanarayan Dutta

    2011-01-01

    Breast cancer is the leading cause of morbidity and mortality in women in the developed world and its incidence in the developing world is on the rise. Management of breast cancer requires a multimodality approach and an integration of the services of surgery, radiation, and medical oncology. Radiotherapy after mastectomy or breast conservation leads to reduction in local recurrence by two-thirds. Recent trials and metaanalyses have also demonstrated overall survival benefit with radiotherapy...

  15. Breast Cancer Diagnosed During Pregnancy: Adapting Recent Advances in Breast Cancer Care for Pregnant Patients

    NARCIS (Netherlands)

    Loibl, S.; Schmidt, A.; Gentilini, O.; Kaufman, B.; Kuhl, C.; Denkert, C.; Minckwitz, G. von; Parokonnaya, A.; Stensheim, H.; Thomssen, C.; Calsteren, K. van; Poortmans, P.; Berveiller, P.; Markert, U.R.; Amant, F.

    2015-01-01

    Breast cancer during pregnancy (BCP), although rare, is becoming more common and treatment should be as similar as possible to that for nonpregnant young patients with breast cancer. A group of specialists convened to review current guidelines and provide guidance on how recent advances in breast ca

  16. Breast thermography. A prognostic indicator for breast cancer survival.

    Science.gov (United States)

    Isard, H J; Sweitzer, C J; Edelstein, G R

    1988-08-01

    A prognostic classification for thermographic staging of breast cancer has been applied to a cohort of 70 patients from 5040 screenees enrolled in the Albert Einstein Medical Center (AEMC) Breast Cancer Detection Demonstration Project (BCDDP). A diagnosis of breast cancer was established in each case before December 31, 1980. None of the patients have been lost to follow-up which extended from a minimum of 6 to a maximum of 13 years. Survival rates for those with favorable, equivocal, and poor thermographic factors are compared with each other and with results in accordance with tumor-node-metastasis (TNM) classification. As of December 31, 1986, there have been 22 (31.4%) deaths, all attributed to breast cancer. The thermographic scoring system clearly shows shorter survival for patients with poor thermographic prognostic factors, 30% surviving at 5 years and only 20% at 10 years compared with overall survival of 80% at 5 years and 70% at 10 years.

  17. The potential role of breast ductoscopy in breast cancer screening.

    Science.gov (United States)

    Sarakbi, W Al; Escobar, Pedro F; Mokbel, Kefah

    2005-01-01

    Breast cancer remains the most common malignancy among women in the Western world. Mammography, which is currently the main screening modality for early detection, has a low positive predictive value of only 25%, especially in young women with very dense breasts. Therefore, new screening approaches are needed for the early detection of breast cancer in all age groups. Mammary ductoscopy (MD) is a newly developed endoscopic technique that allows direct visualization and biopsy of the mammary ductal epithelium where most cancers originate. The procedure can be performed under local anesthesia in the office setting. At present, MD is used as a diagnostic adjunct in patients with pathological nipple discharge and to guide duct excision surgery. This article focuses on the potential of this technique in breast cancer screening and highlights its limitations in this context.

  18. Breast cancer. Part 2: present and future treatment modalities.

    Science.gov (United States)

    Harmer, Victoria

    This is the second article in a series of three on breast cancer. Part 1 discussed breast anatomy, the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging. In this article, treatment for breast cancer is discussed. The article will follow the usual order of modalities in the trajectory, starting with surgery, then chemotherapy, radiotherapy and endocrine treatment, finishing with a discussion of future and biological treatments.

  19. Exercise regulates breast cancer cell viability

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Lillelund, Christian; Midtgaard, Julie

    2016-01-01

    Purpose: Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses......, in breast cancer survivors could regulate breast cancer cell viability in vitro. Methods: Blood samples were collected from breast cancer survivors, partaking in either a 6-month training intervention or across a 2 h acute exercise session. Changes in training parameters and systemic factors were evaluated...... and pre/post exercise-conditioned sera from both studies were used to stimulate breast cancer cell lines (MCF-7, MDA-MB-231) in vitro. Results: Six months of training increased VO2peak (16.4 %, p

  20. Insulin receptor what role in breast cancer?

    Science.gov (United States)

    Papa, V; Costantino, A; Belfiore, A

    1997-10-01

    It is commonly believed that the insulin receptor mainly mediates the metabolic effects of insulin, whereas the closely related IGF-I receptor is considered a major factor for the regulation of cell proliferation. Experimental and epidemiological evidence indicates, however, that insulin and insulin receptors may play an important role in breast cancer. This article reviews evidence indicating that (a) insulin receptors are overexpressed in human breast cancer, (b) insulin stimulates growth in breast cancer cells, (c) cells transfected with human insulin receptor may acquire a ligand-dependent transformed phenotype, and (d) breast cancer is associated with insulin resistance and hyperinsulinemia. These findings may open new possibilities in breast cancer prevention, prognosis assessment, and therapy. (Trends Endocrinol Metab 1997; 8:306-312). (c) 1997, Elsevier Science Inc.

  1. Screening for breast cancer with mammography

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Nielsen, Margrethe

    2009-01-01

    BACKGROUND: A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. OBJECTIVES: To assess the effect of screening for breast cancer with mammography on mortality and morbidity. SEARCH STRATEGY: We searched Pub...... excluded a biased trial and included 600,000 women in the analyses. Three trials with adequate randomisation did not show a significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomisation showed...... a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential...

  2. 乳腺癌中FoxP3表达与上皮间质转化的相关性及其意义%Clinical significance of FoxP3 and the correlation of FoxP3 expression with epithelial-mesenchymal transition in breast cancer

    Institute of Scientific and Technical Information of China (English)

    霍莉莉; 李慧; 魏枫; 赵华; 任秀宝

    2014-01-01

    Objective: This study aims to investigate the correlation between the expression of FoxP3, TGF-β1, and epitheli-al-mesenchymal transition (EMT) in breast cancer and to determine the clinical significance of FoxP3. Methods: The expression of FoxP3, TGF-β1, E-Cadherin, N-Cadherin, Vimentin, and Fibronectin protein were detected in the cancer cells of 74 cases with breast carcinoma via immunohistochemistry. The correlation of FoxP3 protein with clinico-pathologic features of breast carcinoma and the re-lationships among the expressions of FoxP3, TGF-β1, and epithelial-mesenchymal transition (EMT) were analyzed. Results:The ex-pression rates of FoxP3, TGF-β1, and EMT are 36.5%(27/74), 39.2%(29/74), and 40.5%(30/74), respectively. The FoxP3 protein ex-pression in breast cancer is correlated with lymph node metastasis (P0.05). The expression of FoxP3 is also correlated with the expression of TGF-β1. Furthermore, TGF-β1 can induce EMT (P0.05)。FoxP3和TGF-β1的表达之间存在相关性,而TGF-β1可以促进EMT发生(P<0.05)。结论:FoxP3的表达与乳腺癌淋巴结转移和EMT的发生相关,可能作为预测乳腺癌转移可能性的标记物。

  3. SURVIVIN as a marker for quiescent-breast cancer stem cells-An intermediate, adherent, pre-requisite phase of breast cancer metastasis.

    Science.gov (United States)

    Siddharth, Sumit; Das, Sarita; Nayak, Anmada; Kundu, Chanakya Nath

    2016-10-01

    Cancer stem cells drive the metastatic cascade by undergoing epithelial to mesenchymal transition (EMT) and again mesenchymal to epithelial transition (MET). Using multiple breast cancer cell lines including cigarette smoke induced breast cancer cells and tumor derived primary cells from patient sample; we developed a breast cancer metastasis model and reported the existence of an adherent, distinct pre-metastatic phase, quiescent-breast cancer stem cells (Q-BCSCs) prior to attaining an EMT. SURVIVIN was found to be expressed in Q-BCSCs. Time dependant biphasic expression of SURVIVIN in Q-BCSCs reveals that Q-BCSCs is a pre-metastatic phase distinct from both epithelial and mesenchymal counterparts. SURVIVIN favours metastasis and up-regulates WNT/β-CATENIN pathway in a PI3 K/AKT-dependant manner for self-renewal. Knockdown of SURVIVIN in Q-BCSCs lost the metastatic property of cells by inhibiting invasion, EMT-MET, PI3 K/AKT/WNT cascade, and induced apoptosis. Thus, our data suggest the existence of a novel pre-metastatic phase (Q-BCSCs) before EMT and SURVIVIN acts as a marker for Quiescent-BCSCs.

  4. 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.

  5. 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

  6. 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.

  7. Oncogenic role of DDX3 in breast cancer biogenesis.

    Science.gov (United States)

    Botlagunta, M; Vesuna, F; Mironchik, Y; Raman, A; Lisok, A; Winnard, P; Mukadam, S; Van Diest, P; Chen, J H; Farabaugh, P; Patel, A H; Raman, V

    2008-06-26

    Benzo[a]pyrene diol epoxide (BPDE), the active metabolite of benzo[a]pyrene present in tobacco smoke, is a major cancer-causing compound. To evaluate the effects of BPDE on human breast epithelial cells, we exposed an immortalized human breast cell line, MCF 10A, to BPDE and characterized the gene expression pattern. Of the differential genes expressed, we found consistent activation of DDX3, a member of the DEAD box RNA helicase family. Overexpression of DDX3 in MCF 10A cells induced an epithelial-mesenchymal-like transformation, exhibited increased motility and invasive properties, and formed colonies in soft-agar assays. Besides the altered phenotype, MCF 10A-DDX3 cells repressed E-cadherin expression as demonstrated by both immunoblots and by E-cadherin promoter-reporter assays. In addition, an in vivo association of DDX3 and the E-cadherin promoter was demonstrated by chromatin immunoprecipitation assays. Collectively, these results demonstrate that the activation of DDX3 by BPDE, can promote growth, proliferation and neoplastic transformation of breast epithelial cells.

  8. [Association between cadmium and breast cancer].

    Science.gov (United States)

    Strumylaite, Loreta; Bogusevicius, Algirdas; Ryselis, Stanislovas; Pranys, Darius; Poskiene, Lina; Kregzdyte, Rima; Abdrachmanovas, Olegas; Asadauskaite, Rūta

    2008-01-01

    Cadmium is a known human lung carcinogen, although some studies indicate a link between cadmium exposure and human breast cancer. The objective of this study was to assess cadmium concentration in breast tissue samples of patients with breast cancer and benign breast tumor. MATERIAL AND METHODS. The concentration of cadmium was determined in breast tissue samples of 21 breast cancer and 19 benign tumor patients. Two samples of breast tissue from each patient, i.e. tumor and normal tissue close to tumor, were taken for the analysis. Cadmium was determined by atomic absorption spectrometry (Perkin-Elmer, Zeeman 3030). RESULTS. In patients with breast cancer, the mean cadmium concentration was 33.1 ng/g (95% CI, 21.9-44.4) in malignant breast tissue and 10.4 ng/g (95% CI, 5.6-15.2) in normal breast tissue (P=0.002). In patients with benign tumor, the corresponding values were 17.5 ng/g (95% CI, 8.4-26.5) and 11.8 ng/g (95% CI, 5.1-18.5) (P=0.3144). There was a statistically significant difference in cadmium concentration between malignant and benign breast tissues (P=0.009). CONCLUSION. The data obtained show that cadmium concentration is significantly higher in malignant breast tissue as compared with normal breast tissue of the same women or benign breast tissue. Further studies are necessary to determine the association between cadmium concentration in malignant breast tissue and estrogen receptor level, and smoking.

  9. Multidisciplinary Meeting on Male Breast Cancer : Summary and Research Recommendations

    NARCIS (Netherlands)

    Korde, Larissa A.; Zujewski, Jo Anne; Kamin, Leah; Giordano, Sharon; Domchek, Susan; Anderson, William F.; Bartlett, John M. S.; Gelmon, Karen; Nahleh, Zeina; Bergh, Jonas; Cutuli, Bruno; Pruneri, Giancarlo; McCaskill-Stevens, Worta; Gralow, Julie; Hortobagyi, Gabriel; Cardoso, Fatima

    2010-01-01

    Male breast cancer is a rare disease, accounting for less than 1% of all breast cancer diagnoses worldwide. Most data on male breast cancer comes from small single-institution studies, and because of the paucity of data, the optimal treatment for male breast cancer is not known. This article summari

  10. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  11. Use of proteomics for the early diagnosis fo breast cancer

    NARCIS (Netherlands)

    van Winden, A.W.J.

    2010-01-01

    Breast cancer mortality rates in The Netherlands are among the highest in Europe. To improve breast cancer survival, early detection is of vital importance. The introduction of the national breast cancer screening program has led to an improvement in stage distribution at diagnosis of breast cancer.

  12. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

    DEFF Research Database (Denmark)

    Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

    2010-01-01

    PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...

  13. Loss of heterozygosity in bilateral breast cancer.

    Science.gov (United States)

    Kollias, J; Man, S; Marafie, M; Carpenter, K; Pinder, S; Ellis, I O; Blamey, R W; Cross, G; Brook, J D

    2000-12-01

    Women who develop bilateral breast cancer at an early age are likely to harbour germline mutations in breast cancer susceptibility genes. The aim of this study was to test for concordant genetic changes in left and right breast cancer of young women (age < 50) with bilateral breast cancer that may suggest an inherited breast cancer predisposition. Microsatellite markers were used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent to or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (Ataxia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concordant LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each occasion. This may suggest a common mutational event. Four cases showed concordant loss of alleles in both left and right breast cancer at D17S791 (BRCA1). BRCA1 mutations were identified in two of these cases where blood was available. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant LOH was further demonstrated in seven cases for D11S1778 (ATM) and four cases for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer.

  14. Effects of the lifestyle habits in breast cancer transcriptional regulation.

    Science.gov (United States)

    Pérez-Solis, Marco Allán; Maya-Nuñez, Guadalupe; Casas-González, Patricia; Olivares, Aleida; Aguilar-Rojas, Arturo

    2016-01-01

    Through research carried out in the last 25 years about the breast cancer etiology, it has been possible to estimate that less than 10 % of patients who are diagnosed with the condition are carriers of some germline or somatic mutation. The clinical reports of breast cancer patients with healthy twins and the development of disease in women without high penetrance mutations detected, warn the participation more factors in the transformation process. The high incidence of mammary adenocarcinoma in the modern woman and the urgent need for new methods of prevention and early detection have demanded more information about the role that environment and lifestyle have on the transformation of mammary gland epithelial cells. Obesity, alcoholism and smoking are factors that have shown a close correlation with the risk of developing breast cancer. And although these conditions affect different cell regulation levels, the study of its effects in the mechanisms of transcriptional and epigenetic regulation is considered critical for a better understanding of the loss of identity of epithelial cells during carcinogenesis of this tissue. The main objective of this review was to establish the importance of changes occurring to transcriptional level in the mammary gland as a consequence of acute or chronic exposure to harmful products such as obesity-causing foods, ethanol and cigarette smoke components. At analyze the main studies related to topic, it has concluded that the understanding of effects caused by the lifestyle factors in performance of the transcriptional mechanisms that determine gene expression of the mammary gland epithelial cells, may help explain the development of this disease in women without genetic propensity and different phenotypic manifestations of this cancer type.

  15. [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.

  16. Expression status of cyclase‑associated protein 2 as a prognostic marker for human breast cancer.

    Science.gov (United States)

    Xu, Lihua; Peng, Sida; Huang, Qunai; Liu, Yu; Jiang, Hua; Li, Xi; Wang, Jiani

    2016-10-01

    Cyclase-associated protein 2 (CAP2) protein is reported to be upregulated in hepatocellular carcinoma (HCC). However, data regarding its expression pattern and clinical relevance in breast cancer are unknown. The aim of this study was to investigate CAP2 expression and its prognostic significance in breast cancer. CAP2 expression at the mRNA and protein levels was examined by real‑time quantitative-polymerase chain reaction and western blotting in 10 paired breast cancer tissues and adjacent normal tissues. The expression level of CAP2 protein in normal breast epithelial cells and breast cancer cell lines was quantified by western blotting. CAP2 protein expression was analyzed in paraffin‑embedded breast cancer samples, paired adjacent non‑tumor and normal breast tissues by immunohistochemical analysis. Statistical analyses were also performed to evaluate the clinicopathological significance of CAP2 expression. The results showed that the expression of CAP2 mRNA and protein was higher in breast cancer than that noted in the adjacent normal tissues in 10 paired samples. The expression level of CAP2 protein in breast cancer cell lines was higher than that in normal breast epithelial cells. In paraffin‑embedded tissue samples, the expression of CAP2 was higher in breast cancer than that found in the adjacent non‑cancerous tissues and normal breast tissues. Compared with the adjacent non‑cancerous tissues, overexpression of CAP2 was detected in 29.4% (37/126) of the patients. Overexpression of CAP2 was significantly associated with progesterone receptor (PR) expression (p<0.05), and decreased overall survival (OS) (p<0.05). In multivariate analysis, expression of CAP2 was an independent prognostic factor for OS [hazard ratio (HR), 4.821; 95% confidence interval (CI), 2.442‑9.518; p<0.001]. CAP2 is upregulated in breast cancer and is associated with the expression of PR and patient survival. CAP2 may serve as a prognostic indicator for patients

  17. Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

    Science.gov (United States)

    2016-07-29

    Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  18. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Directory of Open Access Journals (Sweden)

    Wendy K Glenn

    Full Text Available BACKGROUND: The purpose of this investigation is to determine if Epstein Barr virus (EBV, high risk human papillomavirus (HPV, and mouse mammary tumour viruses (MMTV co-exist in some breast cancers. MATERIALS AND METHODS: All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis and 14 were predominantly invasive ductal carcinomas (idc. RESULTS: EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%, HPV, 20% and MMTV (32% of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. CONCLUSIONS: We conclude that (i EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  19. OPTIMIZATION OF DIAGNOSTIC IMAGING IN BREAST CANCER

    Directory of Open Access Journals (Sweden)

    S. A. Velichko

    2015-01-01

    Full Text Available The paper presents the results of breast imaging for 47200 women. Breast cancer was detected in 862 (1.9% patients, fibroadenoma in 1267 (2.7% patients and isolated breast cysts in 1162 (2.4% patients. Different types of fibrocystic breast disease (adenosis, diffuse fibrocystic changes, local fibrosis and others were observed in 60.1% of women. Problems of breast cancer visualization during mammography, characterized by the appearance of fibrocystic mastopathy (sclerosing adenosis, fibrous bands along the ducts have been analyzed. Data on the development of diagnostic algorithms including the modern techniques for ultrasound and interventional radiology aimed at detecting early breast cancer have been presented.  

  20. Aetio-pathogenesis of breast cancer

    Directory of Open Access Journals (Sweden)

    Imran Haruna Abdulkareem

    2013-01-01

    Full Text Available This is a literature review on the aetiology and pathogenesis of breast cancer, which is the most common cancer worldwide, and the second leading cause of cancer death, especially in Western countries. Several aetiological factors have been implicated in its pathogenesis, and include age, genetics, family history, diet, alcohol, obesity, lifestyle, physical inactivity, as well as endocrine factors. These factors act separately or together in the causation of breast cancer. More recently, triple negative breast cancer has been described in certain categories of patients and is associated with poorer prognosis and earlier recurrence compared with the conventional breast cancer. Therefore, adequate knowledge of these factors is important in identifying high risk groups and individuals, which will help in screening, early detection and follow-up. This will help to decrease the morbidity and mortality from this life-threatening disease.