Expression of Mitochondrial Progesterone Receptor (PR-M) in Ovarian Cancer and Its Effect on Cell Metastasis Induced by Progesterone

Abstract

Background: PR-M refers to a novel truncated progesterone receptor located on the outer membrane of mitochondria, capable of facilitating the proliferation of leiomyoma cells and breast cancer cells, as well as inhibiting apoptosis as impacted by progesterone or progesterone agonists. However, its role in ovarian tumors has not yet been elucidated.Objective: To study the expression of PR-M in different ovarian tumor tissues and normal tissues, and the effect exerted by progesterone on the proliferation and migration of SKOV-3 cells that achieve high PR-M expression.Methods: Real- time PCR and Western blot were employed for determining PR-M levels in cell lines, non-cancer tissues and ovarian cancer tissues. By immunohistochemistry, PR-M protein expression in benign tumor, borderline tumor and epithelial carcinoma was detected, and the clinicopathological characteristics between PR-M and cancer were analyzed. Furthermore, CCK-8 and scratch test were performed to explore the proliferation and migration of SKOV-3 cells exhibiting high PR-M expression.Results: PR-M increased significantly in cancer tissues and ovarian cancer cell lines, in comparison to normal cells and non-cancer tissues. The abnormal expression showed a significant correlation with intraperitoneal metastasis, lymph node metastasis, clinically related stage and CA125 level, suggesting that high PR-M expression may affect the progression of ovarian tumors. During the cell experiment, PR-M achieved the maximum expression in SKOV-3 cells (PR-A / B(-)). As impacted by progesterone, SKOV-3 cells (PR-A / B(-)) achieved the enhanced proliferation and migration. Besides, the enhancing effect was dose and time-dependent.Conclusion: PR-M is critical to develop ovarian cancer. Progesterone may facilitate the proliferation and migration of ovarian cancer cells exhibiting high PR-M expression.