Estrogen receptor isoform gene expression in ovarian stromal and epithelial tumors

The factors involved in the pathogenesis of ovarian cancers remain unclear, and the response of these tumors to hormonal therapy is limited. The identification of a second estrogen receptor gene (ER beta), expressed predominantly in ovarian granulosa cells, led us to explore its possible role in ovarian cancer, particularly in granulosa cell tumors (GCT). Several isoforms of ER beta have been identified. We sought to define the patterns of both ER alpha and ER beta gene expression in a panel of ovarian tumors consisting of GCT and serous and mucinous cystadenocarcinomas as well as in normal ovary. Expression was determined by RT-PCR using gene- and isoform-specific primers and probes combined with Southern blot analysis of the PCR products. Widespread expression of ER alpha was observed in all tumor types, but at relatively low levels. ER beta is expressed predominantly in GCT, with lower levels in mucinous tumors and very low levels in serous tumors. The ER beta 2 splice variant previously reported in rodents was not observed. Only very low levels of the exon 5, exon 6, and exon 5/6 deletion variants were detected. The C-terminal truncation variant ER beta however, exhibited widespread expression across all the tumor types. As ER beta, has been shown to be a ligand-independent antagonist of ER alpha action, the relative ratios of ER beta(cx), ER alpha, and ER beta may influence the response of a tumor to antiestrogen therapy.