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

Magdalene K. Sgagias, Kay Uwe Wagner, Brad Hamik, Scott Stoeger, Rebecca Spieker, L. Julie Huber, Lewis A. Chodosh, Kenneth H Cowan

Research output: Contribution to journalArticle

38 Scopus citations

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 languageEnglish (US)
Pages (from-to)1451-1456
Number of pages6
JournalCell Cycle
Volume3
Issue number11
DOIs
Publication statusPublished - Nov 2004

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Keywords

  • Bcra1-deficiency
  • Breast cancer
  • CDDP
  • DNA-damage and repair
  • MMS

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Sgagias, M. K., Wagner, K. U., Hamik, B., Stoeger, S., Spieker, R., Huber, L. J., ... Cowan, K. H. (2004). Brca1-deficient murine mammary epithelial cells have increased sensitivity to CDDP and MMS. Cell Cycle, 3(11), 1451-1456. https://doi.org/10.4161/cc.3.11.1211