BRCA1 Inhibition of Estrogen Receptor Signaling in Transfected Cells

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Science  21 May 1999:
Vol. 284, Issue 5418, pp. 1354-1356
DOI: 10.1126/science.284.5418.1354

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Mutations of the breast cancer susceptibility gene BRCA1confer increased risk for breast, ovarian, and prostatic cancers, but it is not clear why the mutations are associated with these particular tumor types. In transient transfection assays, BRCA1 was found to inhibit signaling by the ligand-activated estrogen receptor (ER-α) through the estrogen-responsive enhancer element and to block the transcriptional activation function AF-2 of ER-α. These results raise the possibility that wild-type BRCA1 suppresses estrogen-dependent transcriptional pathways related to mammary epithelial cell proliferation and that loss of this ability contributes to tumorigenesis.

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