Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer

Inheritance of one defective BRCA2 allele predisposes humans to breast canc er, To establish a mouse model for BRCA2-associated breast cancer, we gener ated mouse conditional mutants with BRCA2 and/or p53 inactivated in various epithelial tissues, including mammary-gland epithelium. Although no tumors arose in mice carrying conditional Brca2 alleles, mammary and skin tumors developed frequently in females carrying conditional Brca2 and Trp53 allele s. The presence of one wildtype Brca2 allele resulted in a markedly delayed tumor formation; loss of the wildtype Brca2 allele occurred in a subset of these tumors. Our results show that inactivation of BRCA2 and of p53 combi ne to mediate mammary tumorigenesis, and indicate that disruption of the p5 3 pathway is pivotal in BRCA2-associated breast cancer.