A possible involvement of gender-dependent factors has been postulated in development of human non-small-cell
lung cancers (NSCLC), but its details remain unclear. In this study, we examined biological significance of
progesterone receptor in NSCLCs.
Progesterone receptor immunoreactivity was detected in 106 of 228 NSCLCs (46.5%).
Progesterone receptor-positive NSCLC was frequently detected in female and
adenocarcinoma, and was inversely associated with
tumor-node-
metastasis stage and histologic differentiation.
Progesterone receptor status was also associated with better clinical outcome of the patients, and a multivariate analysis revealed
progesterone receptor status as an independent prognostic factor.
Progesterone-synthesizing
enzymes were detected in NSCLCs, and tissue concentration of
progesterone was higher in these cases (n = 42). Immunoblotting analyses showed the presence of
progesterone receptor in three NSCLC cell lines (A549, LCSC#2, and 1-87), but not in RERF-LC-OK or PC3. Transcriptional activities of
progesterone receptor were increased by
progesterone in these three
progesterone receptor-positive NSCLC cells by
luciferase assays. Cell proliferation was inhibited by
progesterone in these
progesterone receptor-positive NSCLC cells in a dose-dependent manner, which was inhibited by
progesterone receptor blocker. Proliferation of these
tumor cells injected into nude mice was also dose-dependently inhibited by
progesterone, with a concomitant increase of p21 and p27 and a decrease of
cyclin A,
cyclin E, and Ki67. Results of our present study suggested that
progesterone receptor was a potent prognostic factor in NSCLCs and
progesterone inhibited growth of
progesterone receptor-positive NSCLC cells. Therefore,
progesterone therapy may be clinically effective in suppressing development of
progesterone receptor-positive NSCLC patients.