Journal
GENES & DEVELOPMENT
Volume 15, Issue 10, Pages 1188-1193Publisher
COLD SPRING HARBOR LAB PRESS
DOI: 10.1101/gad.879201
Keywords
Brca1; mouse mutant; mammary tumors
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Funding
- NCI NIH HHS [P01 CA75553, R21 CA66224] Funding Source: Medline
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We generated mouse mutants carrying in the Brca1 locus a modification (Brca1(tr)) that eliminates the C-terminal half of the protein product and obtained results indicating that, depending on genetic background, the missing BRCT and/or other domains are dispensable for survival, but essential for tumor suppression. Most of the apparently hypomorphic Brca1(tr/tr) mutants developed various tumors. Lymphomas were detected at all ages, whereas sarcomas and carcinomas, including breast cancer, appeared after a long latency. The mammary tumors showed striking variability in histopathological patterns suggesting stochastic engagement of tumorigenic pathways in their progression, to which the Brca1(tr/tr) mutation was apparently a late participant.
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