Estrogen receptor {beta}1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells.
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.
Treeck
Oliver
O
Department of Obstetrics and Gynecology, Klinik für Frauenheilkunde und Geburtshilfe, University of Regensburg, Landshuter Strasse 65, 93053 Regensburg, Germany. otreeck@caritasstjosef.de
Pfeiler
Georg
G
Mitter
Diana
D
Lattrich
Claus
C
Piendl
Gerhard
G
Ortmann
Olaf
O
D017398:Alternative Splicing; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods; D014945:Wound Healing
D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D034741:RNA, Small Interfering