RT Journal Article SR Electronic T1 Prevention of Brca1-Mediated Mammary Tumorigenesis in Mice by a Progesterone Antagonist JF Science JO Science FD American Association for the Advancement of Science SP 1467 OP 1470 DO 10.1126/science.1130471 VO 314 IS 5804 A1 Poole, Aleksandra Jovanovic A1 Li, Ying A1 Kim, Yoon A1 Lin, Suh-Chin J. A1 Lee, Wen-Hwa A1 Lee, Eva Y.-H. P. YR 2006 UL http://science.sciencemag.org/content/314/5804/1467.abstract AB Women with mutations in the breast cancer susceptibility gene BRCA1 are predisposed to breast and ovarian cancers. Why the BRCA1 protein suppresses tumor development specifically in ovarian hormone–sensitive tissues remains unclear. We demonstrate that mammary glands of nulliparous Brca1/p53-deficient mice accumulate lateral branches and undergo extensive alveologenesis, a phenotype that occurs only during pregnancy in wild-type mice. Progesterone receptors, but not estrogen receptors, are overexpressed in the mutant mammary epithelial cells because of a defect in their degradation by the proteasome pathway. Treatment of Brca1/p53-deficient mice with the progesterone antagonist mifepristone (RU 486) prevented mammary tumorigenesis. These findings reveal a tissue-specific function for the BRCA1 protein and raise the possibility that antiprogesterone treatment may be useful for breast cancerpreventioninindividuals with BRCA1 mutations.