Breast cancer is the most commonly occurring cancer in women and the second most common
cancer overall. By the age of 80, the estimated risk for breast cancer for women with
germline BRCA1 or BRCA2 mutations is around 80%. Genetically engineered BRCA1-deficient
mouse models offer a unique opportunity to study the pathogenesis and therapy of triple
negative breast cancer. Here we present a newly established Brca1−/−, p53−/− mouse
mammary tumor cell line, designated as CST. CST shows prominent features of BRCA1-mutated
triple-negative breast cancers including increased motility, high proliferation rate,
genome instability and sensitivity to platinum chemotherapy and PARP inhibitors (olaparib,
veliparib, rucaparib and talazoparib). Genomic instability of CST cells was confirmed
by whole genome sequencing, which also revealed the presence of COSMIC (Catalogue
of Somatic Mutations in Cancer) mutation signatures 3 and 8 associated with homologous
recombination (HR) deficiency. In vitro sensitivity of CST cells was tested against
11 chemotherapy agents. Tumors derived from orthotopically injected CST-mCherry cells
in FVB-GFP mice showed sensitivity to cisplatin, providing a new model to study the
cooperation of BRCA1-KO, mCherry-positive tumor cells and the GFP-expressing stromal
compartment in therapy resistance and metastasis formation. In summary, we have established
CST cells as a new model recapitulating major characteristics of BRCA1-negative breast
cancers.
