BRCA1 involvement in toxicological responses and human cancer etiology.

Breast cancer associated gene 1 (BRCA1) gene is located on the long (q) arm of chromosome 17 at position 21. In the nucleus of many types of normal cells, BRCA1 protein interacts with several other proteins to mend strand breaks in DNA. It is generally considered a key regulatory protein participating in cell cycle checkpoint and DNA damage repair networks. Exposure to various environmental and genetic factors can induce a severe impact on life span and lead to neoplastic transformation. BRCA1 through its participation in the control mechanisms of cell growth and DNA repair is lately considered as an important component of mammary homeostasis. In this review we summarize the different cellular functions and roles of this gene, the experimental evidence for its linkage to carcinogenesis and recent evidence tying BRCA1 to environmentally induced toxic-stress responses. Finally, we discuss the new insights in the exploitation of BRCA1 defects for the development of new therapeutic strategies in cancer treatment and clinical applications.