Progesterone signaling inhibits cervical carcinogenesis in mice.
Progesterone signaling inhibits cervical carcinogenesis in mice.
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DOI：
10.1016/j.ajpath.2013.07.026
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发表时间：
2013-11
期刊：
影响因子：
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通讯作者：
Y. Yoo;Jieun Son;F. F. Mehta-F.;F. DeMayo;J. Lydon;S. Chung
中科院分区：
文献类型：
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作者：
Y. Yoo;Jieun Son;F. F. Mehta-F.;F. DeMayo;J. Lydon;S. Chung
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 oncogenesE6and/orE7has 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 carcinogenesisin vivo.
