Estrogen receptor beta 1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells

Estrogen receptor (ER) beta 1 and its splice variants are expressed both in ovary and ovarian cancer. We studied the role of ER beta 1 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 ER beta 1 or its splice variants ER beta-delta 125 and ER beta-delta 1256, and tested their response to estrogen and tamoxifen in comparison with the untransfected cells. Heterologous expression of ER beta 1, but not of the exon-deleted ER beta 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 ER beta 1 ligand independently also exhibited an increased apoptosis rate and a significantly decreased motility, an effect accompanied by upregulation of fibulin 1c. Our data demonstrate that ER beta 1, 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 ER alpha.