Abstract 959: ERα1 represses breast cancer EMT by inhibiting EGFR-mediated downregulation of E-cadherin

Abstract

Abstract Although epithelial to mesenchymal transition (EMT) is associated with specific breast cancer phenotypes, such as the basal-like and claudin-low tumors, there is a lack of validated markers, which can distinguish tumors with poor clinical outcome and high metastatic potential. Estrogen receptor beta (ERα) has been shown to regulate invasion in prostate cancer. However, it is still unclear if ERα by influencing invasion can predict metastasis in breast cancer. Here we show that wild-type ERα (ERα1) inhibits EMT and invasion in basal-like breast cancer cells when they grow either in vitro or in vivo in zebrafish. This correlates with an ERα1-mediated upregulation of miR-200a, miR-200b and miR-429 and the subsequent repression ZEB1 and SIP1, which results in increased expression of E-cadherin. Downregulation of the basal marker EGFR was found to be involved in the ERα1-mediated mesenchymal to epithelial transition since induction of EGFR expression or treatment with EGF abolished the ability of ERα1 to sustain the epithelial phenotype. This inverse correlation of ERα1 with EGFR and its positive association with epithelial markers was additionally observed in breast cancer specimens. These results strengthen the association of ERα1 with the regulation of EMT and propose the receptor as potential crucial marker in predicting survival and metastasis in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 959. doi:1538-7445.AM2012-959