No abstract

Estrogen receptor beta (ERβ) mediates the effects of estrogens in a variety of human tissues and regulates cellular processes involved in initiation and progression of breast cancer such as cell proliferation and migration. Clinical studies produced contradictory data regarding the role for ERβ in prognosis of metastatic breast cancer and the molecular mechanism through which ERβ influences cell migration and invasion has not been fully elucidated. Here we show that induction of ERβ expression inhibits epithelial to mesenchymal transition (EMT) in metastatic breast cancer cells. This correlates with an ERβ-mediated induction in the expression of the epithelial marker E-cadherin and downregulation of its transcriptional repressors ZEB1 and SIP1. ERβ alters the expression of ZEB1 and SIP1 by inducing the expression of the miR-200a, miR200b and miR-429. Downregulation of these miRNAs in ERβ-expressing cells resulted in decreased cell-cell contact and decline of E-cadherin levels. In addition, ERβ was found to inhibit the invasiveness of metastatic breast cancer cells in a zebrafish xenotransplantation model. We are now examining breast cancer specimens derived from ductal carcinomas and metaplastic breast cancers to see whether ERβ levels decline in the mesenchymal regions and ERβ expression is correlated with epithelial markers. These data propose a crucial role for ERβ in the regulation of EMT and in prognosis of invasive and metastatic breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-04.