PES1 differentially regulates the expression of ER[alpha] and ER[beta] in ovarian cancer

Estrogen exhibits mitogenic activity in early ovarian carcinogenesis and plays an important role in ovarian tumorigenesis. Due to the increased expression of ER[alpha] and decreased expression of the ER[beta], the ratio of ER[alpha] and ER[beta] is markedly increased in ovarian cancer. We have recently reported that PES1 regulates the balance of ER[alpha] and ER[beta] at the post-transcriptional level in breast cancer. Here, we report that PES1 inversely regulates the expression of ER[alpha] and ER[beta] in addition to their transcriptional activities in epithelial ovarian cancer. We found that the ablation of PES1 resulted in the significant downregulation of ER[alpha] and estrogen-responsive genes such as cylin D1, HIF-1[alpha] and VEGF and the up-regulation of ER[beta] and p21WAF1. Cell proliferation in both tested ovarian cell lines was markedly inhibited and cells were arrested in G2 after PES1 was ablated. Further analysis of clinical samples showed that expression of PES1 correlated positively with ER[alpha] expression and negatively with ER[beta] expression. Our results demonstrate that PES1 may play important role in the progression of ovarian cancer by inversely regulating the ER[alpha] and ER[beta] expression. PES1 may be a new target for ovarian cancer therapy. © 2013 IUBMB Life, 65(12):1017-1025, 2013. [PUBLICATION ABSTRACT]