Estrogen receptor β1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells

Abstract

Estrogen receptor (ER) β1 and its splice variants expressed both in ovary and ovarian cancer. We studied the role of ERβ1 and two of its splice variants in regulation of gene expression, cellular proliferation, apoptosis, and migration of an ovarian cancer cell line. In this study, we transfected SK-OV-3 ovarian cancer cells with vectors coding for ERβ1 or its splice variants ERβ-δ125 and ERβ-δ1256, and tested their response to estrogen and tamoxifen in comparison with the untransfected cells. Heterologous expression of ERβ1, but not of the exon-deleted ERβ variants resulted in notably slower cell growth of SK-OV-3 ovarian cancer cells, an effect accompanied by more than tenfold increase of cyclin-dependent kinase inhibitor p21(WAF1) transcript levels and a significant reduction of cyclin A2 mRNA levels. SK-OV-3 cells stably overexpressing ERβ1 ligand independently also exhibited an increased apoptosis rate and a significantly decreased motility, an effiect accompanied by upregulation of fibulin 1c. Our data demonstrate that ERβ1, but not the exon-deleted isoforms tested exerts multiple antitumoral effects on SK-OV-3 ovarian cancer cells even in the absence of estradiol or functional ERα. © 2007 Society for Endocrinology.