Cell proliferation by estrogen in the absence of BRCA1 protein may lead to a high mutation rate, thereby increasing the risk of acquiring cancer causing mutations (Scully and Livingston, 2000). The breast tissue is the target for estrogen and other hormones that are shown to endow antiapoptotic survival function upon cells sometimes in a non-autonomous manner. BRCA1 regulates DNA repair and apoptosis. In the absence of BRCA1 protein apoptosis does not occur to check the proliferation induced by estrogen leading to tumors (Forgez et al., 2000; Scully and Livingston, 2000). BRCA1 has also been implicated in the regulation of transcription, and it is possible that it may regulate genes expressed only in the breast. The altered expression of these transcripts would lead to an increase in neoplastic transformation through as yet undefined mechanisms. BRCA1 plays an inhibitory role in ER signaling that could explain the tissue specificity since breast tissue is a major target of ER action. A fact relevant to this is that most BRCA1 tumors lack ER expression (Fan et al., 2001; Vincent-Salomon et al., 2007). Decreased amount of BRCA1 protein resulting from either mutations or promoter hypermethylation has been associated with both familial and sporadic breast cancer.
Keyword: Tissue specificity, breast cancer, BRCA1, hormones, 17β HSD.
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