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 (Brca1fl/f1) and then immortalized by infection with HPV-16E6 retrovirus to degrade p53 protein. Brca1-/- AAMECs were generated by deletion of exon 11 following transduction of Brca1fl/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 a role 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.
Original language | English (US) |
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Pages (from-to) | 1451-1456 |
Number of pages | 6 |
Journal | Cell Cycle |
Volume | 3 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2004 |
Keywords
- Bcra1-deficiency
- Breast cancer
- CDDP
- DNA-damage and repair
- MMS
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology