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- Title
Genomic Analyses as a Guide to Target Identification and Preclinical Testing of Mouse Models of Breast Cancer.
- Authors
Bennett, Christina N.; Green, Jeffrey E.
- Abstract
Cross-species genomic analyses have proven useful for identifying common genomic alterations that occur in human cancers and mouse models designed to recapitulate human tumor development. High-throughput molecular analyses provide a valuable tool for identifying particular animal models that may represent aspects of specific subtypes of human cancers. Corresponding alterations in gene copy number and expression in tumors from mouse and human suggest that these conserved changes may be mechanistically essential for cancer development and progression, and therefore, they may be critical targets for therapeutic intervention. Using a cross-species analysis approach, mouse models in which the functions of p53, Rb, and BRCA1 have been disrupted demonstrate molecular features of human, triple-negative (ER-, PR-, and ERBB2-), basal-type breast cancer. Using mouse tumor models based on the targeted abrogation of p53 and Rb function, we identified a large, integrated genetic network that correlates to poor outcome in several human epithelial cancers. This gene signature is highly enriched for genes involved in DNA replication and repair, chromosome maintenance, cell cycle regulation, and apoptosis. Current studies are determining whether inactivation of specific members within this signature, using drugs or siRNA, will identify potentially important new targets to inhibit triple-negative, basal-type breast cancer for which no targeted therapies currently exist.
- Subjects
GENOMICS; MICE; ANIMAL models in research; BREAST cancer research; GENES; DNA replication; DNA repair; APOPTOSIS
- Publication
Toxicologic Pathology, 2010, Vol 38, Issue 1, p88
- ISSN
0192-6233
- Publication type
Article
- DOI
10.1177/0192623309357074