Department of Cancer Biology
BRCA1 Protein; Tumor Suppressor Protein p53; Breast Neoplasms
Breast cancers that are "triple-negative" for the clinical markers ESR1, PGR, and HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53, and Brca1 pathways are each associated with triple-negative and Basal-like subtypes. Our mouse genetic studies demonstrate that the combined inactivation of Rb and p53 pathways is sufficient to suppress the physiological cell death of mammary involution. Furthermore, concomitant inactivation of all three pathways in mammary epithelium has an additive effect on tumor latency and predisposes highly penetrant, metastatic adenocarcinomas. The tumors are poorly differentiated and have histologic features that are common among human Brca1-mutated tumors, including heterogeneous morphology, metaplasia, and necrosis. Gene expression analyses demonstrate that the tumors share attributes of both Basal-like and Claudin-low signatures, two molecular subtypes encompassed by the broader, triple-negative class defined by clinical markers.
Rights and Permissions
Copyright: © 2012 Kumar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS Genet. 2012 Nov;8(11):e1003027. doi: 10.1371/journal.pgen.1003027. Link to article on publisher's site
Kumar, Prashant; Mukherjee, Malini; Johnson, Jacob P. S.; Patel, Milan; Huey, Bing; Albertson, Donna G.; and Simin, Karl, "Cooperativity of Rb, Brca1, and p53 in malignant breast cancer evolution" (2012). Open Access Articles. 2377.