Editors' ChoiceMEDICINE

Progesterone and Breast Cancer

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Science's STKE  05 Dec 2006:
Vol. 2006, Issue 364, pp. tw411
DOI: 10.1126/stke.3642006tw411

Mutations in the breast cancer susceptibility gene BRCA1 greatly increase a woman’s risk of developing breast and ovarian cancers. Why do these mutations predominantly affect hormone-responsive tissues when the mutant gene is widely expressed throughout the body? Poole et al. (see the news story by Marx) suggest that this tissue specificity is caused in part by BRCA1-mediated effects on signaling by the hormone progesterone. Mammary epithelial cells (MECs) of Brca-1/p53-deficient mice accumulated high levels of progesterone receptors, probably through defective degradation by the proteasome, and developed aberrant proliferation of the MECs. Treatment with the progesterone antagonist mifepristone (RU 486) prevented or delayed mammary tumor development in the mice.

A. J. Poole, Y. Li, Y. Kim, S.-C. J. Lin, W.-H. Lee, E. Y.-H. P. Lee, Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science 314, 1467-1470 (2006). [Abstract] [Full Text]

J. Marx, Squelching progesterone’s signal may prevent breast cancer. Science 314, 1370 (2006). [Summary] [Full Text]

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