| First Author | Poole AJ | Year | 2006 |
| Journal | Science | Volume | 314 |
| Issue | 5804 | Pages | 1467-70 |
| PubMed ID | 17138902 | Mgi Jnum | J:116190 |
| Mgi Id | MGI:3693151 | Doi | 10.1126/science.1130471 |
| Citation | Poole AJ, et al. (2006) Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science 314(5804):1467-70 |
| abstractText | 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 cancer prevention in individuals with BRCA1 mutations. |
