Regulation of Ovarian Cancer Cell Viability and Sensitivity to Cisplatin by Progesterone Receptor Membrane Component-1

Abstract

These findings indicate that PGRMC1 plays an important role in promoting ovarian cancer cell viability and that attenuating PGRMC1's action makes the ovarian cancer cells more sensitive to CDDP. These data suggest that targeted depletion of PGRMC1 could be useful as an adjunct to CDDP therapy.

Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells

“…PGRMC1 expression is elevated in several cancer cells like lung, breast, and ovarian cancer (3)(4)(5). Further, in ovarian cancer PGRMC1 expression is increased in advanced cancer stages (3).…”

“…Further, in ovarian cancer PGRMC1 expression is increased in advanced cancer stages (3). The protein promotes cell survival and chemotherapy resistance (5,6) and therefore may be an interesting therapeutic target for the intervention of cancer (5-7).…”

“…Deletion of PGRMC1 in different cancer cell lines results in higher sensitivity of these cells towards the anti-cancer drugs cisplatin, doxorubicin and camptothecin, while overexpression of PGRMC1 renders cells more resistant against these drugs (3,8). In vitro studies revealed that PGRMC1 depleted cells show a slower rate of cell proliferation (6).…”

Steroid Hormones and Ovarian Cancer

“…However, the actions of progesterone in ovarian carcinomas is complex, and clinical trials utilizing progesterone have not proved as promising as in vivo and in vitro observations. In part, this may be due to the action of progesterone receptor membrane component 1 (PGRMC1), which recently in vitro was found to promote ovarian tumor cell proliferation, while its depletion slows cellular growth (Peluso et al, 2008). In vivo, PGRMC1-depleted mice had fewer and smaller tumors, again supporting the pro-oncogenic nature of PGRMC1 (Peluso et al, 2009).…”

Progestogens and Breast Cancer Risk – In Vitro Investigations with Human Benign and Malignant Epithelial Breast Cells

“…However, because bacterially expressed PGRMC1 does not bind to progesterone (Min et al, 2005), and since the majority of PGRMC1 is not localized to the plasma membrane (Crudden et al, 2005;Nolte et al, 2000;Peluso et al, 2008) it is now tentatively assumed that PGRMC1 does not bind P4 by itself (Cahill, 2007), but requires an unknown protein that is associated only in partially purified PGRMC1 preparations (Peluso et al, 2008). PGRMC1-associated progesterone binding is functionally important in cancer cells because progesterone inhibits apoptosis in granulosa cells, and this anti-apoptotic activity requires PGRMC1 (Peluso et al, 2008a(Peluso et al, , 2008b. However, it is unclear how PGRMC1 transduces anti-apoptotic signaling by progesterone.…”