scholarly journals Microarray analysis of RhoC-transformed mammary epithelial cells suggests molecular mechanisms of inflammatory breast cancer

10.1038/87212 ◽  
2001 ◽  
Vol 27 (S4) ◽  
pp. 73-73
Author(s):  
Sofia Merajver ◽  
Zhi-Fen Wu ◽  
Tammy Chang ◽  
Hamid Mirshahidi ◽  
Paul Meltzer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Microarray Analysis ◽  
Inflammatory Breast Cancer ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial

scholarly journals Protein Microarray Analysis of Mammary Epithelial Cells from Obese and Nonobese Women at High Risk for Breast Cancer: Feasibility Data

2011 ◽  
Vol 20 (3) ◽  
pp. 476-482 ◽  
Author(s):  
Patrick G. Pilie ◽  
Catherine Ibarra-Drendall ◽  
Michelle M. Troch ◽  
Gloria Broadwater ◽  
William T. Barry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Epithelial Cells ◽  
Microarray Analysis ◽  
Mammary Epithelial Cells ◽  
Protein Microarray ◽  
Mammary Epithelial ◽  
Protein Microarray Analysis

scholarly journals Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells

2020 ◽  
Vol 21 (10) ◽  
pp. 3735 ◽  
Author(s):  
Vidhya A Nair ◽  
Satu Valo ◽  
Päivi Peltomäki ◽  
Khuloud Bajbouj ◽  
Wael M. Abdel-Rahman
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Bisphenol A ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Environmental Contaminants ◽  
Cancer Cell Line ◽  
Mammary Epithelial ◽  
Cancer Development ◽  
Molecular Alterations

There is an ample epidemiological evidence to support the role of environmental contaminants such as bisphenol A (BPA) in breast cancer development but the molecular mechanisms of their action are still not fully understood. Therefore, we sought to analyze the effects of three common contaminants (BPA; 4-tert-octylphenol, OP; hexabromocyclododecane, HBCD) on mammary epithelial cell (HME1) and MCF7 breast cancer cell line. We also supplied some data on methoxychlor, MXC; 4-nonylphenol, NP; and 2-amino-1-methyl-6-phenylimidazo [4–b] pyridine, PhIP. We focused on testing the prolonged (two months) exposure to low nano-molar concentrations (0.0015–0.0048 nM) presumed to be oncogenic and found that they induced DNA damage (evidenced by upregulation of pH2A.X, pCHK1, pCHK2, p-P53) and disrupted the cell cycle. Some agents induced epigenetic (methylation) changes of tumor suppressor genes TIMP3, CHFR, ESR1, IGSF4, CDH13, and GSTP1. Obviously, the accumulation of these molecular alterations is an essential base for cancer development. Consistent with this, we observed that these agents increased cellular invasiveness through collagen. Cellular abilities to form colonies in soft agar were increased for MCF7. Toxic agents induced phosphorylation of protein kinase such as EGFR, CREB, STAT6, c-Jun, STAT3, HSP6, HSP27, AMPKα1, FAK, p53, GSK-3α/β, and P70S6 in HME1. Most of these proteins are involved in potential oncogenic pathways. Overall, these data clarify the molecular alterations that can be induced by some common environmental contaminants in mammary epithelial cells which could be a foundation to understand environmental carcinogenesis.

scholarly journals Attenuation of TGF-β signaling suppresses premature senescence in a p21-dependent manner and promotes oncogenic Ras-mediated metastatic transformation in human mammary epithelial cells

2012 ◽  
Vol 23 (8) ◽  
pp. 1569-1581 ◽  
Author(s):  
Shu Lin ◽  
Junhua Yang ◽  
Abdel G. Elkahloun ◽  
Abhik Bandyopadhyay ◽  
Long Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Dependent Manner ◽  
Human Mammary Epithelial Cells ◽  
Major Player ◽  
Human Mammary Epithelial ◽  
Basal Like Breast Cancer

The molecular mechanisms that drive triple-negative, basal-like breast cancer progression are elusive. Few molecular targets have been identified for the prevention or treatment of this disease. Here we developed a series of isogenic basal-like human mammary epithelial cells (HMECs) with altered transforming growth factor-β (TGF-β) sensitivity and different malignancy, resembling a full spectrum of basal-like breast carcinogenesis, and determined the molecular mechanisms that contribute to oncogene-induced transformation of basal-like HMECs when TGF-β signaling is attenuated. We found that expression of a dominant-negative type II receptor (DNRII) of TGF-β abrogated autocrine TGF-β signaling in telomerase-immortalized HMECs and suppressed H-Ras-V12–induced senescence-like growth arrest (SLGA). Furthermore, coexpression of DNRII and H-Ras-V12 rendered HMECs highly tumorigenic and metastatic in vivo in comparison with H-Ras-V12–transformed HMECs that spontaneously escaped H-Ras-V12–induced SLGA. Microarray analysis revealed that p21 was the major player mediating Ras-induced SLGA, and attenuated or loss of p21 expression contributed to the escape from SLGA when autocrine TGF-β signaling was blocked in HMECs. Furthermore, knockdown of p21 also suppressed H-Ras-V12–induced SLGA. Our results identify that autocrine TGF-β signaling is an integral part of the cellular anti-transformation network by suppressing the expression of a host of genes, including p21-regulated genes, that mediate oncogene-induced transformation in basal-like breast cancer.

scholarly journals The ETS Transcription Factor ESE-1 Transforms MCF-12A Human Mammary Epithelial Cells via a Novel Cytoplasmic Mechanism

2004 ◽  
Vol 24 (12) ◽  
pp. 5548-5564 ◽  
Author(s):  
Jason D. Prescott ◽  
Karen S. N. Koto ◽  
Meenakshi Singh ◽  
Arthur Gutierrez-Hartmann
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Nuclear Localization ◽  
Human Breast Cancer ◽  
Mammary Epithelial Cells ◽  
Cell Transformation ◽  
Mammary Epithelial ◽  
Human Breast ◽  
Human Mammary Epithelial

ABSTRACT Several different transcription factors, including estrogen receptor, progesterone receptor, and ETS family members, have been implicated in human breast cancer, indicating that transcription factor-induced alterations in gene expression underlie mammary cell transformation. ESE-1 is an epithelium-specific ETS transcription factor that contains two distinguishing domains, a serine- and aspartic acid-rich (SAR) domain and an AT hook domain. ESE-1 is abundantly expressed in human breast cancer and trans-activates epithelium-specific gene promoters in transient transfection assays. While it has been presumed that ETS factors transform mammary epithelial cells via their nuclear transcriptional functions, here we show (i) that ESE-1 protein is cytoplasmic in human breast cancer cells; (ii) that stably expressed green fluorescent protein-ESE-1 transforms MCF-12A human mammary epithelial cells; and (iii) that the ESE-1 SAR domain, acting in the cytoplasm, is necessary and sufficient to mediate this transformation. Deletion of transcriptional regulatory or nuclear localization domains does not impair ESE-1-mediated transformation, whereas fusing the simian virus 40 T-antigen nuclear localization signal to various ESE-1 constructs, including the SAR domain alone, inhibits their transforming capacity. Finally, we show that the nuclear localization of ESE-1 protein induces apoptosis in nontransformed mammary epithelial cells via a transcription-dependent mechanism. Together, our studies reveal two distinct ESE-1 functions, apoptosis and transformation, where the ESE-1 transcription activation domain contributes to apoptosis and the SAR domain mediates transformation via a novel nonnuclear, nontranscriptional mechanism. These studies not only describe a unique ETS factor transformation mechanism but also establish a new paradigm for cell transformation in general.

scholarly journals ZFHX3 Promotes the Proliferation and Tumor Growth of ER-Positive Breast Cancer Cells Likely by Enhancing Stem-Like Features and MYC and TBX3 Transcription

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3415
Author(s):  
Ge Dong ◽  
Gui Ma ◽  
Rui Wu ◽  
Jinming Liu ◽  
Mingcheng Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Progesterone Receptors ◽  
Mammary Epithelial ◽  
Luciferase Reporter ◽  
Mammosphere Formation

Breast cancer is a common malignancy, but the understanding of its cellular and molecular mechanisms is limited. ZFHX3, a transcription factor with many homeodomains and zinc fingers, suppresses prostatic carcinogenesis but promotes tumor growth of liver cancer cells. ZFHX3 regulates mammary epithelial cells’ proliferation and differentiation by interacting with estrogen and progesterone receptors, potent breast cancer regulators. However, whether ZFHX3 plays a role in breast carcinogenesis is unknown. Here, we found that ZFHX3 promoted the proliferation and tumor growth of breast cancer cells in culture and nude mice; and higher expression of ZFHX3 in human breast cancer specimens was associated with poorer prognosis. The knockdown of ZFHX3 in ZFHX3-high MCF-7 cells decreased, and ZFHX3 overexpression in ZFHX3-low T-47D cells increased the proportion of breast cancer stem cells (BCSCs) defined by mammosphere formation and the expression of CD44, CD24, and/or aldehyde dehydrogenase 1. Among several transcription factors that have been implicated in BCSCs, MYC and TBX3 were transcriptionally activated by ZFHX3 via promoter binding, as demonstrated by luciferase-reporter and ChIP assays. These findings suggest that ZFHX3 promotes breast cancer cells’ proliferation and tumor growth likely by enhancing BCSC features and upregulating MYC, TBX3, and others.

scholarly journals AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG

2020 ◽  
Vol 175 ◽  
pp. 113904
Author(s):  
Noelia Miret ◽  
C. Daniel Zappia ◽  
Gabriela Altamirano ◽  
Carolina Pontillo ◽  
Lorena Zárate ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial

scholarly journals Ductal tree ablation by local delivery of ethanol prevents tumor formation in an aggressive mouse model of breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Elizabeth Kenyon ◽  
Jennifer J. Westerhuis ◽  
Maximilian Volk ◽  
Jeremy Hix ◽  
Shatadru Chakravarty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Prophylactic Mastectomy ◽  
Treated Group ◽  
Tumor Formation ◽  
Mammary Epithelial ◽  
Tumor Incidence ◽  
Control Group ◽  
Untreated Control Group

Abstract Background Prophylactic mastectomy is the most effective intervention to prevent breast cancer. However, this major surgery has life-changing consequences at the physical, emotional, psychological, and social levels. Therefore, only high-risk individuals consider this aggressive procedure, which completely removes the mammary epithelial cells from which breast cancer arises along with surrounding tissue. Here, we seek to develop a minimally invasive procedure as an alternative to prophylactic mastectomy by intraductal (ID) delivery of a cell-killing solution that locally ablates the mammary epithelial cells before they become malignant. Methods After ID injection of a 70% ethanol-containing solution in FVB/NJ female animals, ex vivo dual stained whole-mount tissue analysis and in vivo X-ray microcomputed tomography imaging were used to visualize ductal tree filling, and histological and multiplex immunohistochemical assays were used to characterize ablative effects and quantitate the number of intact epithelial cells and stroma. After ID injection of 70% ethanol or other solutions in cancer-prone FVB-Tg-C3(1)-TAg female animals, mammary glands were palpated weekly to establish tumor latency and examined after necropsy to record tumor incidence. Statistical difference in median tumor latency and tumor incidence between experimental groups was analyzed by log-rank test and logistic mixed-effects model, respectively. Results We report that ID injection of 70% ethanol effectively ablates the mammary epithelia with limited collateral damage to surrounding stroma and vasculature in the murine ductal tree. ID injection of 70% ethanol into the mammary glands of the C3(1)-TAg multifocal breast cancer model significantly delayed tumor formation (median latency of 150 days in the untreated control group [n = 25] vs. 217 days in the ethanol-treated group [n = 13], p value < 0.0001) and reduced tumor incidence (34% of glands with tumors [85 of 250] in the untreated control group vs. 7.3% of glands with tumor [7 of 95] in the ethanol-treated group, risk ratio = 4.76 [95% CI 1.89 to 11.97, p value < 0.0001]). Conclusions This preclinical study demonstrates the feasibility of local ductal tree ablation as a novel strategy for primary prevention of breast cancer. Given the existing clinical uses of ethanol, ethanol-based ablation protocols could be readily implemented in first-in-human clinical trials for high-risk individuals.

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