Estrogen Inhibits Epithelial Progesterone Receptor-dependent Progestin Therapy Efficacy in a Mouse Model of Cervical Cancer

Am J Pathol. 2021 Nov 10:S0002-9440(21)00469-7. doi: 10.1016/j.ajpath.2021.10.008. Online ahead of print.ABSTRACTWhile the uterine cervix responds to the female sex hormone change, the role of progesterone in cervical cancer is poorly understood. It has been shown that medroxyprogesterone acetate (MPA) regresses cervical cancer in the transgenic mouse model expressing human papillomavirus type 16 (HPV16) E6 and E7 oncogenes. As MPA interacts most strongly with progesterone receptor (PR), we reasoned that PR would contribute to MPA-induced regression of cervical cancer. We also hypothesized that estrogen influences the therapeutic activity of MPA because it promotes cervical cancer growth in the same mouse model. In the present study, we found that the deletion of Pgr in the cervical cancer cells ablated the MPA's therapeutic effect in the HPV transgenic mouse model. We also discovered that estrogen attenuated cancer regression by MPA in the same model system. These observations indicate that MPA can effectively regress cervical cancer only when cancer cells express PR and estrogen levels are low. Our results suggest that, if translatable, MPA should be administered when estrogen levels are low in patients with PR-positive cervical cancer.PMID:34774516 | DOI:10.1016/j.ajpath.2021.10.008
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research