Progesterone signaling inhibits cervical carcinogenesis in mice

Young A. Yoo, Jieun Son, Fabiola F. Mehta, Francesco J. Demayo, John P. Lydon, Sang Hyuk Chung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Human papillomavirus is the main cause of cervical cancer, yet other nonviral cofactors are also required for the disease. The uterine cervix is a hormone-responsive tissue, and female hormones have been implicated in cervical carcinogenesis. A transgenic mouse model expressing human papillomavirus oncogenes E6 and/or E7 has proven useful to study a mechanism of hormone actions in the context of this common malignancy. Estrogen and estrogen receptor α are required for the development of cervical cancer in this mouse model. Estrogen receptor α is known to up-regulate expression of the progesterone receptor, which, on activation by its ligands, either promotes or inhibits carcinogenesis, depending on the tissue context. Here, we report that progesterone receptor inhibits cervical and vaginal epithelial cell proliferation in a ligand-dependent manner. We also report that synthetic progestin medroxyprogesterone acetate promotes regression of cancers and precancerous lesions in the female lower reproductive tracts (ie, cervix and vagina) in the human papillomavirus transgenic mouse model. Our results provide the first experimental evidence that supports the hypothesis that progesterone signaling is inhibitory for cervical carcinogenesis in vivo.

Original languageEnglish (US)
Pages (from-to)1679-1687
Number of pages9
JournalAmerican Journal of Pathology
Volume183
Issue number5
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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