scholarly journals Dual Epigenetic Regulation of ERα36 Expression in Breast Cancer Cells

2019 ◽  
Vol 20 (11) ◽  
pp. 2637 ◽  
Author(s):  
Charlène Thiebaut ◽  
Amand Chesnel ◽  
Jean-Louis Merlin ◽  
Maelle Chesnel ◽  
Agnès Leroux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Epithelial Cells ◽  
Methylation Status ◽  
Acquired Resistance ◽  
Good Prognosis ◽  
Mammary Epithelial ◽  
Endogenous Expression ◽  
Epigenetic Modulation

Breast cancer remains the major cause of cancer-induced morbidity and mortality in women. Among the different molecular subtypes, luminal tumors yet considered of good prognosis often develop acquired resistance to endocrine therapy. Recently, misregulation of ERα36 was reported to play a crucial role in this process. High expression of this ERα isoform was associated to preneoplastic phenotype in mammary epithelial cells, disease progression, and enhanced resistance to therapeutic agents in breast tumors. In this study, we identified two mechanisms that could together contribute to ERα36 expression regulation. We first focused on hsa-miR-136-5p, an ERα36 3’UTR-targeting microRNA, the expression of which inversely correlated to the ERα36 one in breast cancer cells. Transfection of hsa-miR136-5p mimic in MCF-7 cells resulted in downregulation of ERα36. Moreover, the demethylating agent decitabine was able to stimulate hsa-miR-136-5p endogenous expression, thus indirectly decreasing ERα36 expression and counteracting tamoxifen-dependent stimulation. The methylation status of ERα36 promoter also directly modulated its expression level, as demonstrated after decitabine treatment of breast cancer cell and confirmed in a set of tumor samples. Taken together, these results open the way to a direct and an indirect ERα36 epigenetic modulation by decitabine as a promising clinical strategy to counteract acquired resistance to treatment and prevent relapse.

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 Benign mammary epithelial cells enhance the transformed phenotype of human breast cancer cells

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Joanna M Poczobutt ◽  
John Tentler ◽  
Xian Lu ◽  
Pepper J Schedin ◽  
Arthur Gutierrez-Hartmann
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Human Breast Cancer Cells ◽  
Human Breast

Ligand-independent activation of the arylhydrocarbon receptor by ETK (Bmx) tyrosine kinase helps MCF10AT1 breast cancer cells to survive in an apoptosis-inducing environment

2011 ◽  
Vol 392 (10) ◽  
pp. 897-908 ◽  
Author(s):  
Yasuko Fujisawa ◽  
Wen Li ◽  
Dalei Wu ◽  
Patrick Wong ◽  
Christoph Vogel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Epithelial Cells ◽  
Specific Inhibitor ◽  
Mammary Epithelial ◽  
Serum Starvation ◽  
Arylhydrocarbon Receptor ◽  
Induced Apoptosis

Abstract It has been reported that the arylhydrocarbon receptor (AHR) is overexpressed in certain types of breast tumors. However, so far no concrete evidence has been provided yet as to why and how the overexpressed AHR in those cancer cells is functionally activated without exogenous ligands. Here we show that the AHR was functionally activated when estrogen receptor-negative, AHR overexpressing MCF10AT1 human breast cancer cells (designated P20E) were subjected to serum starvation. Transfection of cells with ETK-KQ, a plasmid for kinase-dead epithelial and endothelial tyrosine kinase (ETK), attenuated this AHR activation. Artificial over-expression of ETK in P20E cells through transfection with wild-type ETK plasmid (ETK-wt) caused up-regulation of cytochrome P4501a1 (CYP1A1; a marker of functional activation of AHR). Furthermore, ablation of ETK expression by a specific antisense oligonucleotide or AG879, a specific inhibitor of ETK kinase suppressed activation of AHR induced by omeprazole, a strong ligand-independent activator of AHR. Activation of ETK in those cells conferred them resistance to UVB- as well as doxorubicin-induced apoptosis, both of which were reversed by ETK-KQ. Together, these findings support our conclusion that ETK is the tyrosine kinase responsible for the functional activation of the AHR in these mammary epithelial cells.

GPCR-induced migration of breast carcinoma cells depends on both EGFR signal transactivation and EGFR-independent pathways

2005 ◽  
Vol 386 (9) ◽  
pp. 845-855 ◽  
Author(s):  
Stefan Hart ◽  
Oliver M. Fischer ◽  
Norbert Prenzel ◽  
Esther Zwick-Wallasch ◽  
Matthias Schneider ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Epithelial Cells ◽  
Growth Factor Receptor ◽  
Mammary Epithelial ◽  
Cellular Processes ◽  
Mitogenic Signalling ◽  
Epidermal Growth ◽  
G Protein Coupled

Abstract The epidermal growth factor receptor (EGFR) plays a key role in the regulation of important cellular processes under normal and pathophysiological conditions such as cancer. In human mammary carcinomas the EGFR is involved in regulating cell growth, survival, migration and metastasis and its activation correlates with the lack of response in hormone therapy. Here, we demonstrate in oestrogen receptor-positive and -negative human breast cancer cells and primary mammary epithelial cells a cross-communication between G protein-coupled receptors (GPCRs) and the EGFR. We present evidence that specific inhibition of ADAM15 or TACE blocks GPCR-induced and proHB-EGF-mediated EGFR tyrosine phosphorylation, downstream mitogenic signalling and cell migration. Notably, activation of the PI3K downstream mediator PKB/Akt by GPCR ligands involves the activity of sphingosine kinase (SPHK) and is independent of EGFR signal transactivation. We conclude that GPCR-induced chemotaxis of breast cancer cells is mediated by EGFR-dependent and -independent signalling pathways, with both parallel pathways having to act in concert to achieve a complete migratory response.

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