Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia and Cancer and Prolongs Lifespan in a Pten Loss-of-Function-Induced Cancer Model

Authors

Nicole C Kelp
Cindy A Pru
Sandeep Paudel
John P Lydon
J Julie Kim
John J Peluso
James K Pru

Language

English

Publication Date

3-31-2025

Journal

Cancers

DOI

10.3390/cancers17071178

PMID

40227710

PMCID

PMC11988108

PubMedCentral® Posted Date

3-31-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The expression of members of the progesterone receptor membrane component (PGRMC) family, particularly PGRMC1, is elevated in diverse types of cancers, particularly those of the female reproductive system. While xenograft tumor studies using human transformed cell lines in immunocompromised mice have suggested that PGRMC1 enhances tumor growth and chemoresistance, the exact role of members of the PGRMC family in cancer development in vivo remains unclear. In this study, we examined the effect of deleting Pgrmc2 on the development of endometrial hyperplasia and cancer using a murine phosphatase and tensin homologue (Pten) conditional loss-of-function model. We previously established that PGRMCs are cell survival factors that are required for normal estrogen-induced uterine epithelial cell proliferation and normal female fertility. The deletion of Pgrmc2 reduced the incidence and severity of endometrial hyperplasia and cancer in mice with conditional Pten-heterozygous uteri and increased lifespan in mice with conditional Pten-knockout uteri. Mechanistically, the deletion of Pgrmc2 decreased uterine glandular epithelial cell proliferation. Pten loss-of-function-induced endometrial hyperplasia and cancer elevated uterine inflammation, but this was not impacted by PGRMC2 deficiency. This study identifies PGRMC2 as a potential therapeutic target to be inhibited in the treatment of endometrial hyperplasia and cancer, particularly where PTEN activity is reduced due to gene mutation or loss.

Keywords

cancer, endometrial, hyperplasia, PGRMC1, PGRMC2, progesterone, PTEN, uterus

Published Open-Access

yes

Recommended Citation

Kelp, Nicole C; Pru, Cindy A; Paudel, Sandeep; et al., "Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia and Cancer and Prolongs Lifespan in a Pten Loss-of-Function-Induced Cancer Model" (2025). Faculty and Staff Publications. 4883.
https://digitalcommons.library.tmc.edu/baylor_docs/4883