Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer.
Nat Genet
; 29(4): 418-25, 2001 Dec.
Article
em En
| MEDLINE
| ID: mdl-11694875
ABSTRACT
Inheritance of one defective BRCA2 allele predisposes humans to breast cancer. To establish a mouse model for BRCA2-associated breast cancer, we generated 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 alleles. 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 combine to mediate mammary tumorigenesis, and indicate that disruption of the p53 pathway is pivotal in BRCA2-associated breast cancer.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Mamárias Animais
/
Genes p53
/
Genes Supressores de Tumor
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Proteína BRCA2
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Modelos Animais de Doenças
Limite:
Animals
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article