Treeck Oliver, Pfeiler Georg, Mitter Diana, Lattrich Claus, Piendl Gerhard, Ortmann Olaf
Department of Obstetrics and Gynecology, Klinik für Frauenheilkunde und Geburtshilfe, University of Regensburg, Landshuter Strasse 65, 93053 Regensburg, Germany.
J Endocrinol. 2007 Jun;193(3):421-33. doi: 10.1677/JOE-07-0087.
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.
雌激素受体（ER）β1及其剪接变体在卵巢和卵巢癌中均有表达。我们研究了ERβ1及其两种剪接变体在卵巢癌细胞系的基因表达调控、细胞增殖、凋亡和迁移中的作用。在本研究中，我们用编码ERβ1或其剪接变体ERβ-δ125和ERβ-δ1256的载体转染SK-OV-3卵巢癌细胞，并与未转染的细胞比较，测试它们对雌激素和他莫昔芬的反应。ERβ1的异源表达，而非外显子缺失的ERβ变体，导致SK-OV-3卵巢癌细胞的生长明显减慢，这种效应伴随着细胞周期蛋白依赖性激酶抑制剂p21（WAF1）转录水平增加超过十倍以及细胞周期蛋白A2 mRNA水平显著降低。稳定过表达ERβ1配体独立的SK-OV-3细胞也表现出凋亡率增加和运动性显著降低，这种效应伴随着纤连蛋白1c的上调。我们的数据表明，即使在没有雌二醇或功能性ERα的情况下，ERβ1而非所测试的外显子缺失异构体对SK-OV-3卵巢癌细胞具有多种抗肿瘤作用。
