Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cells

C. N. Kundu, R. Balusu, A. S. Jaiswal, C. G. Gairola, S. Narayan

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Our previous studies have shown that treatment with cigarette smoke condensate (CSC) transforms normal breast epithelial cell line, MCF-10A. In the present study, the mechanism of CSC-induced transformation of breast epithelial cells was examined. We first determined whether benzo[a]pyrene (B[a]P)- and CSC-induced levels of APC are capable of inhibiting long-patch base excision repair (LP-BER) since our earlier studies had shown that an interaction of APC with DNA polymerase β (pol-β) blocks strand-displacement synthesis. With the use of a novel in vivo LP-BER assay, it was demonstrated that increased and decreased APC levels in different breast cancer cell lines were associated with a decrease or increase in LP-BER activity, respectively. The effect of APC on LP-BER in malignant and pre-malignant breast epithelial cell lines was produced by either overexpression or knockdown of APC. Furthermore, it was shown that the decreased LP-BER in B[a]P- or CSC-treated pre-malignant breast epithelial cells is associated with an increased level of APC and decreased cell growth. Our results suggest that the decreased growth allows cells to repair the damaged DNA before mitosis, and failure to repair damaged DNA has the potential to transform pre-malignant breast epithelial cells.

Original languageEnglish (US)
Pages (from-to)1428-1438
Number of pages11
JournalOncogene
Volume26
Issue number10
DOIs
StatePublished - Mar 1 2007

Keywords

  • Adenomatous polyposis coli
  • Benzo[a]pyrene
  • Breast carcinogenesis
  • Cigarette smoke condensate
  • Long-patch base excision repair

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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