Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1 -mutated basal-like breast cancer

• DOI: 10.1073/pnas.0702969104
• Publication Date: 2007-07-12T01:04:57Z
• Authors: Xiaoling Liu; Henne Holstege; Hanneke van der G...; Marcelle Treur-Mu...; John Zevenhoven; Arno Velds; Ron M. Kerkhoven; Martin H. van Vliet; Lodewyk F. A. Wes...; Johannes L. Peterse; Anton Berns; Jos Jonkers
• Keywords: Basal (medicine); Progesterone receptor; BRCA2 Protein

Women carrying germ-line mutations in BRCA1 are strongly predisposed to developing breast cancers with characteristic features also observed sporadic basal-like cancers. They appear as high-grade tumors high proliferation rates and pushing borders. On the molecular level, they negative for hormone receptors ERBB2, display frequent TP53 mutations, express basal epithelial markers. To study role of P53 loss function cancer development, we generated conditional mouse models tissue-specific mutation Brca1 and/or p53 cells. Somatic both resulted rapid efficient formation highly proliferative, poorly differentiated, estrogen receptor-negative mammary carcinomas borders increased expression markers, reminiscent human cancer. BRCA1- p53-deficient exhibit dramatic genomic instability, their signatures resemble those -mutated Thus, these important hallmarks hereditary -mutation carriers.