Estrogen receptor (ER) beta1 and its splice variants are expressed both in ovary and
ovarian cancer. We studied the role of ERbeta1 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 ERbeta1 or its splice variants ERbeta-delta125 and ERbeta-delta1256, and tested their response to
estrogen and
tamoxifen in comparison with the untransfected cells. Heterologous expression of ERbeta1, but not of the exon-deleted
ERbeta 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 ERbeta1
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 ERbeta1, 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
ERalpha.