Altered expression of the DNA repair- protein, N-methylpurine-DNA glycosylase (MPG), in breast cancer

Sonia R. Cerda, Patrick W. Turk, Ann D. Thor, Sigmund A. Weitzman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

We examined expression of N-methylpurine-DNA glycosylase (MPG), a DNA repair enzyme that removes N-alkylpurine damage, in normal, malignant, and immortalized breast epithelial cells, and breast cancer cell lines (MDA-MB-231, MCF7, T47D). Northern analysis showed increased expression in cancer versus normal breast epithelial cells (2-24-fold). Southern blots revealed no gene amplification or polymorphisms. Immunofluorescence, immunohistochemistry, and Western blot analysis demonstrated increased MPG protein expression in the tumor cells that correlated with elevated glycosylase activity. Since MPG overexpression has been shown to be paradoxically associated with increased susceptibility to DNA damage, up-regulation of this gene may suggest a functional role in breast carcinogenesis.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalFEBS Letters
Volume431
Issue number1
DOIs
StatePublished - Jul 10 1998

Funding

We gratefully acknowledge Dr. Benilde Jimenez, Meredith Gonzales, and Angela Cisneros for technical assistance with cloning of recombinant proteins, immunofluorescence, and HPLC techniques respectively, and Dr. Jonathan Jones for the use of the Zeiss Photomicroscope III. We are grateful to Dr. S. Mitra (University of Texas Medical Branch) for providing us with the cloned cDNA encoding human MPG; Dr. T. Lukas (Northwestern University Medical Center) for the design of the peptides; and Dr. T. O'Connor (City of Hope, Beckman Research Institute, CA) for supplying us with the purified human MPG protein. This study was supported by the US Army (DAMD17-94-J-4466), the Lynn Sage Cancer Research Foundation, and the National Institute of Health (AG11536).

Keywords

  • Alkylpurine
  • Breast cancer
  • DNA repair
  • N-methylpurine-DNA glycosylase

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Cell Biology

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