Brca1-Deficient Murine Mammary Epithelial Cells have Increased Sensitivity to CDDP and MMS

Abstract

In this report we describe the isolation of an isogenic pair of Brca1(++) and Brca1(-/-) murine mammary epithelial cells (MMECs). These cells were isolated from Brca1 conditional knock out mice which contained loxP sites flanking exon 11 of the Brca1 gene (Brca1(fl/f1)) and then immortalized by infection with HPV-16E6 retrovirus to degrade p53 protein. Brca1(-/-) MMECs were generated by deletion of exon 11 following transduction of Brca1(fl/f1) MMECs with a retroviral vector expressing Cre recombinase. Brca1-deficiency rendered MMECs sensitive to cis-platinum (II) diamine dichloride (CDDP) and methylmethane sulfonate (MMS). The Brca1(+/+) and Brca1(-/-) MMECS is the only known pair of isogenic mammary epithelial cell lines. The understanding of the mechanisms of the CDDP sensitivity of the BRCA1-deficient mammary epithelial cells would be very important in understanding how BRCA1-deficiency plays out in tissue specific breast cancer chemotherapy. These studies support the role of BRCA1 in the CDDP-induced and MMS-induced DNA damage and repair by p53-independent pathways.