Brca1-deficient murine mammary epithelial cells have increased sensitivity to CDDP and MMS

Cell Cycle. 2004 Nov;3(11):1451-6. doi: 10.4161/cc.3.11.1211. Epub 2004 Nov 8.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Cell Cycle
  • Cell Line, Transformed*
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Inhibitory Concentration 50
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / drug effects
  • Methyl Methanesulfonate / pharmacology*
  • Mice
  • Mice, Knockout
  • Organoplatinum Compounds / pharmacology*
  • Time Factors

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • Organoplatinum Compounds
  • Methyl Methanesulfonate