Mammary tumor formation in p53- and BRCA1-deficient mice

The inheritance of a mutant copy of the BRCA1 gene greatly increases a woma n's lifetime risk for ovarian and breast cancer. While a homologous gene ha s been identified in mouse, mice carrying mutations in this gene do not dis play a detectable increase in tumor formation, To determine whether mutatio ns in p53 might increase the incidence of tumors associated with the loss o f BRCA1 function in mice, we have generated mice carrying mutations at both of these loci. We report here that the presence of a mutant Brca1 allele d oes not alter survival of either p53(-/-) or p53(+/+) mice. Although the tu mor spectrum was not dramatically altered, an increased incidence of mammar y tumors was observed in the Brca1(+/-)p53(-/-) mice, Four mammary tumors w ere seen in the Brca1(+/-)p53(-/-) group whereas only one such tumor was se en among the p53(-/-) control group. In addition, although the presence of a mutant Brca1 allele did not alter the survival rate or the incidence of m ost tumor types in the p53(+/-) mice, 5 of the 23 tumors isolated from the Brca1(+/-)p53(-/-) mice treated with ionizing radiation were of mammary epi thelial origin, and 3 of these had lost expression of the wild-type Brca1 g ene. In contrast, no such tumors were observed in the irradiated p53(+/-) c ontrols. Although the number of mammary tumors observed in these animals is small, these results are suggestive of a role for BRCA1 in mammary tumor f ormation after exposure to specific DNA damaging agents.