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- Title
Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer.
- Authors
Jonkers, Jos; Meuwissen, Ralph; van der Gulden, Hanneke; Peterse, Hans; van der Valk, Martin; Berns, Anton
- 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 1353 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 1353 combine to mediate mammary tumorigenesis, and indicate that disruption of the 1353 pathway is pivotal in BRCA2-associated breast cancer.
- Subjects
TUMOR suppressor genes; GENETICS of breast cancer; LABORATORY mice
- Publication
Nature Genetics, 2001, Vol 29, Issue 4, p418
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng747