Differential expression of progesterone receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors

Abstract

Human epithelial ovarian neoplasm is well-known to be sex steroid-related, but the possible biological significance of progesterone actions in these tumors remains controversial. In this study, we examined the differential expression patterns of the two progesterone receptor (PR) isoforms, PRA and PRB, using immunohistochemistry and real-time quantitative RT-PCR in normal and neoplastic ovarian tissues, and in cell lines derived from a normal ovarian surface epithelium and an ovarian epithelial carcinoma in order to further elucidate the possible involvement of progesterone in the development of ovarian neoplasms. The median H scores for PR isoforms in normal (n = 8), benign (n = 10), borderline (n = 8) and malignant (n = 24) ovarian tissues were as follows; PRA: 194.0, 171.0, 49.5, 0 (P < 0.05), and PRB: 175.0, 180.5, 251.5, 168.5, respectively. In ovarian cancer cell lines (OVCAR-3 and Caov-3), the PRB / PRAB mRNA ratio was increased by 17beta-estradiol, both time- and dose-dependently. However, this ratio was unaltered following the addition of 17beta-estradiol in a normal ovarian epithelial cell line (NOV-31). Immunoblotting analysis demonstrated that PRB protein expression was markedly up-regulated in OVCAR-3, whereas the PRA and PRB isoforms both appeared to be increased in NOV-31. These results suggest that down-regulation of PRA is associated with the development of ovarian epithelial carcinoma.