title: The cancer connection: BRCA1 and BRCA2 tumor suppression in mice and humans.
abstract: BRCA1 and BRCA2 mutations are estimated to be responsible for the great majority of familial breast and ovarian cancers. Much progress has been made toward the understanding of the function of these proteins through genetic, biochemical, and structural studies. The embryonic lethality encountered in the knockout mouse initially hindered the development of mouse models aimed at studying tumor suppression. However, mice that harbor hypomorphic Brca1 and Brca2 alleles and cre-mediated tissue-specific deletions for Brca1 and Brca2 have been generated. Mice deficient for either Brca1 or Brca2 sustain a wide range of carcinoma and mammary epithelium deleted for Brca1 or Brca2 is highly susceptible to mammary tumorigenesis. Mammary (and other) tumors occur at long latency as compared to oncogene-induced mouse tumors. p53 deficiency is highly cooperative with both Brca1 and Brca2 in promoting tumorigenesis. Analysis of Brca1-associated mammary tumors reveals significant similarities to BRCA1-associated breast cancer in regard to high tumor grade, hormone receptor negativity, a high incidence of p53 mutations and genetic instability.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. moynaham@mskcc.org
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Moynahan
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics; D004195:Disease Models, Animal; D005313:Fetal Death / Q000235:genetics; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D016159:Tumor Suppressor Protein p53