BRCA1-associated tumorigenesis: what have we learned from knockout mice?
A series of allelic mutations in the tumor suppressor Brca1 have been created to study mechanisms underlying BRCA1-associated tumorigenesis. Brca1 is essential in maintaining genome integrity through its involvement in DNA damage repair, G(2)-M cell-cycle checkpoint and centrosome duplication. The loss of Brca1 is not sufficient for malignant transformation, rather, it triggers multiple genetic alterations, including the inactivation of p53 and activation of a number of oncogenes, that ultimately result in mammary tumorigenesis.
Brodie
S G
SG
Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Deng
C X
CX
D000483:Alleles; D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D016158:Genes, p53; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009154:Mutation