Are Trp53 rescue of Brca1 embryonic lethality and Trp53/Brca1 breast cancer association related?
Brca1 is involved in multiple biological pathways including DNA damage repair, transcriptional regulation, and cell-cycle progression. A complex pattern of interactions of Brca1 with Trp53 has also emerged. Xu and coworkers found that haploid loss of Trp53 significantly reduces the embryonic lethality observed in mice with a homozygous in-frame deletion of Brca1 exon 11. They report that widespread apoptosis correlates with the embryonic lethality resulting from this homozygous delta11 Brca1 mutation. A mechanism responsible for Brca1-associated carcinogenesis is proposed. These experiments extend our knowledge of a complex Brca1/Trp53 relationship. However, the precise mechanisms through which Brca1 interacts with Trp53 to suppress mammary tumor formation have yet to be elucidated.
McAllister
Kimberly A
KA
Laboratory of Women's Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. mcallis2@niehs.nih.gov
Wiseman
Roger W
RW
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D005804:Genes, Lethal; D016158:Genes, p53; D015674:Mammary Neoplasms, Animal / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009154:Mutation
D019313:BRCA1 Protein