Abstract 2079: Estrogen receptor alpha expression with miR-206 trans-acting regulation roles in breast cancer cell lines

Abstract

Abstract Estrogen receptor-alpha (ER-α) is present in 65% of human breast tumors. Tamoxifen(Tam) was only effective in ER-α expressed breast cancer cell lines. Also, it was reported that miR-206 decreases endogenous ER-α mRNA and protein levels in human MCF-7 breast cancer cells. We expect that effect of invasion and apoptosis in breast cancer cells by regulating expression of miR-206. Hence, we demonstrated that trans-acting regulation roles by ER-α and miR-206 in breast cancer cell line. MCF-7(ER hyper-expressed), MDA-MB231(ER hypo-expressed), MCF-10A(ER hypo-expressed normal breast cell line) cells were targeted experiments. Cell viability was analyzed by dose-dependent Tamoxifen with MTT assay. Whole-cell extracts were observed for protein levels of ER-α, ERK, p38, p-ATM, ATM, p-chk2, chk2, p-p53, p53, cyclinD1 with western blotting. By using, ER-α, p38, miR206 activator/inhibitor and real-time PCR, we studied change of molecules in cell lines. Cell viability of MCF-7 cell was reduced about 85% of the cells were dead by 5, 7μM Tam. ERK phosphorylation was increased by dose-dependent Tam in both MCF-7 cell and by 7μM Tam treatment in MDA-MB231 cell. Also, p38 phosphorylation was raised by dose-dependent Tam in MCF-7 cells and MDA-MB231 cells. ATM, chk2, p53 that involved DNA damage molecules were not affect by dose-dependent Tam. CyclinD1 known as cell cycle G1 regulation molecule was decrease by effect of Tam. Also, miR-206 levels by real-time PCR were lessening in MCF-7 and increase in MDA-MB231 and MCF-10A. Specific molecules of MCF-7, MDA-MB231 and MCF-10A were influenced by ER-α, p38, miR-206 activator/inhibitor. ER-α regulation and miR-206 expression were shown to trans-activated roles in breast cancer cell lines. Therefore, inhibition of miR-206 was accompanying the hyper-sensitivity of anticancer drug Tamoxifen that mediated ER-α. Whereas, miR-206 over expressed put down the invasion properties of breast cancer. We suggest that these roles of miR-206 will take the strategy for valuable breast cancer therapy. Keywords: ER-α, miR-206, Tamoxifen, breast cancer Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2079.