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.