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http://dx.doi.org/10.5352/JLS.2022.32.11.882

BCAR3 Activates the Estrogen Response Element through the PI3-kinase/Akt Pathway in Human Breast MCF-12A Cells  

Myung-Ju, Oh (Ministry of Food and Drug Safety)
Joo-Yeon, Ha (College of Nanoscience and Nanotechnology, Pusan National University)
Byung H., Jhun (College of Nanoscience and Nanotechnology, Pusan National University)
Publication Information
Journal of Life Science / v.32, no.11, 2022 , pp. 882-889 More about this Journal
Abstract
Breast cancer anti-estrogen resistance 3 (BCAR3) has been identified as one of the genes that induces anti-estrogen resistance in breast cancer. We have previously reported that BCAR3 activates promoters of c-Jun, activator protein-1, and the serum response element. In this study, we investigated the functional role of BCAR3 in the activation of the estrogen response element (ERE) in normal human breast MCF-12A cells. Transient expression of BCAR3 induced ERE activation, which was further increased by 17β-estradiol treatment but was not blocked by the anti-estrogen tamoxifen. Next, we studied the signaling pathway of BCAR3 leading to ERE activation. BCAR3-mediated ERE activation was inhibited by LY294002 and AZD5363, inhibitors of the phosphatidylinositol (PI) 3-kinase pathway, but not by PD98059 and U0126, inhibitors of the mitogen-activated protein kinase pathway. ERE activation was induced by the catalytic subunit p110α. of PI3-kinase or the active mutant of Akt, and this activation was not further increased by additional BCAR3 transfection. Based on these results, we propose that BCAR3 plays an important role in ERE activation through the PI3-kinase/Akt pathway in human breast MCF-12A cells.
Keywords
Anti-estrogen; BCAR3; estrogen response element; signaling pathway; PI3-kinase;
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