Abstract A19: Progesterone receptor signaling inhibits cervical cancer
| Autor: | Jieun Son, Young Yoo, Fabiola F. Mehta, John P. Lydon, Sang-Hyuk Chung, Francesco J. DeMayo |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Molecular Cancer Research. 12:A19-A19 |
| ISSN: | 1557-3125 1541-7786 |
| DOI: | 10.1158/1557-3125.modorg-a19 |
| Popis: | Human papillomavirus (HPV) is the major etiological factor for cervical cancer, which remains third most frequent and fourth most deadly malignancy in women worldwide. However, evidence indicates that other non-viral cofactors are also required for the disease. The uterine cervix is sensitive to female hormones, which have been implicated in cervical carcinogenesis. A transgenic mouse model expressing HPV oncogenes E6 and/or E7 is relevant to human cancer. We use this model to study a mechanism of hormone actions in the context of this common malignancy. Estrogen and estrogen receptor α (ERα) are required for the development of cervical cancer in this mouse model. ERα is known to upregulate expression of the progesterone receptor (PR), which, upon activation by its ligands, either promotes or inhibits carcinogenesis depending on the tissue context. In the present study, we demonstrate that progesterone-PR signaling inhibits cervical and vaginal epithelial cell proliferation in a ligand-dependent manner. We also demonstrate that synthetic progestin medroxyprogesterone acetate (MPA) promotes regression of cancers and precancerous lesions in the female lower reproductive tracts (i.e., cervix and vagina). Our results provide the first experimental evidence supporting that the progesterone signaling is inhibitory for cervical cancer in vivo. Our results also suggest that cervical cancer recurs if MPA treatment is ceased. They imply that MPA efficiently get rid of bulk of disease, yet cancer progenitor/stem cells remain. Our mouse model provides a unique opportunity to interrogate mechanism of PR and PR ligands in cervical cancer. Citation Format: Fabiola Mehta, Young A Yoo, Jieun Son, Francesco J. DeMayo, John P. Lydon, Sang-Hyuk Chung. Progesterone receptor signaling inhibits cervical cancer. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr A19. |
| Databáze: | OpenAIRE |
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