| Literature DB >> 33262282 |
Olga Kim1, Eun Young Park1, Sun Young Kwon2, Sojin Shin3, Robert E Emerson4, Yong-Hyun Shin1, Francesco J DeMayo5, John P Lydon6, Donna M Coffey7, Shannon M Hawkins8, Lawrence A Quilliam1, Dong-Joo Cheon9, Facundo M Fernández10, Kenneth P Nephew11, Adam R Karpf12, Martin Widschwendter13,14,15, Anil K Sood16,17, Robert C Bast18, Andrew K Godwin19, Kathy D Miller20, Chi-Heum Cho21, Jaeyeon Kim22.
Abstract
Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.Entities:
Keywords: BRCA; antiprogestins; hormone; ovarian cancer; progesterone
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Year: 2020 PMID： 33262282 PMCID： PMC7749341 DOI： 10.1073/pnas.2013595117
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205