A mouse model featuring tissue-specific deletion of p53 and Brca1 gives rise to mammary tumors with genomic and transcriptomic similarities to human basal-like breast cancer

摘要: In human basal-like breast cancer, mutations and deletions in TP53 BRCA1 are frequent oncogenic events. Thus, we interbred mice expressing the CRE-recombinase with harboring loxP sites at (K14-Cre; p53f/f Brca1f/f) to test hypothesis that tissue-specific deletion of would give rise tumors reflective cancer. support our hypothesis, these transgenic developed express cytokeratins demonstrated intrinsic gene expression features similar tumors. Array comparative genomic hybridization revealed a striking conservation copy number alterations between K14-Cre; Brca1f/f mouse model Conserved events included MYC amplification, KRAS RB1 loss. Microarray analysis demonstrated DNA also led corresponding changes signatures pathway activation including high proliferation due matched cancer for propensity have immune cell infiltrates. Given long latency (~ 250 days), created tumor syngeneic transplant lines, as well vitro which were tested sensitivity carboplatin paclitaxel. These therapies invoked acute regression, extended overall survival, resulted an anti-tumor response. findings demonstrate this is valuable preclinical resource study