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Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20057, USA. emr36@georgetown.edu
Mutations of the breast cancer susceptibility gene BRCA1 are linked to hereditary early onset breast and breast-ovarian cancer syndromes. These mutations confer an increased risk for other hormone-dependent cancers, including those of the uterus, cervix and prostate. BRCA1 expression is decreased or absent in a significant proportion of sporadic breast and ovarian cancers, suggesting a wider role in these tumor types. Multiple functions for BRCA1 have been identified, including roles in DNA repair, cell-cycle progression and apoptosis. These functions are consistent with a tumor suppressor activity, but they do not explain why BRCA1 mutation carriers develop hormone-responsive cancer types. Recent studies indicate that BRCA1 interacts with and regulates the activity of estrogen receptor alpha (ER alpha) and the androgen receptor. Its expression is regulated by carcinogens and anticarcinogens that modulate ER alpha signaling, suggesting a molecular linkage between BRCA1 and hormone-responsive cancers.
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