Progesterone Receptor Membrane Component (PGRMC)1 and PGRMC2 and Their Roles in Ovarian and Endometrial Cancer

SIMPLE SUMMARY: Ovarian and endometrial cancers occur frequently and can be lethal. Recently, progesterone receptor membrane component (PGRMC) 1 and PGRMC2 have been shown to be highly expressed in these cancers and play important roles in promoting tumor growth and chemoresistance. This review will focus on the mechanisms through which these two PGRMC family members influence the growth of ovarian and endometrial cancers. The mechanisms highlighted in this review could also provide insights into the roles that these PGRMCs play in regulating the fate of other PGRMC-expressing cancers such as lung, breast, and pancreatic cancer. ABSTRACT: Cancers of the female reproductive tract are both lethal and highly prevalent. For example, the five-year survival rate of women diagnosed with ovarian cancer is still less than 50%, and endometrial cancer is the fourth most common cancer in women with > 65,000 new cases in the United States in 2020. Among the many genes already established as key participants in ovarian and endometrial oncogenesis, progesterone receptor membrane component (PGRMC)1 and PGRMC2 have gained recent attention given that there is now solid correlative information supporting a role for at least PGRMC1 in enhancing tumor growth and chemoresistance. The expression of PGRMC1 is significantly increased in both ovarian and endometrial cancers, similar to that reported in other cancer types. Xenograft studies using human ovarian and endometrial cancer cell lines in immunocompromised mice demonstrate that reduced expression of PGRMC1 results in tumors that grow substantially slower. While the molecular underpinnings of PGRMCs’ mechanisms of action are not clearly established, it is known that PGRMCs regulate survival pathways that attenuate stress-induced cell death. The objective of this review is to provide an overview of what is known about the roles that PGRMC1 and PGRMC2 play in ovarian and endometrial cancers, particularly as related to the mechanisms through which they regulate mitosis, apoptosis, chemoresistance, and cell migration.