Increased expression and no mutation of the Flap endonuclease (FEN1) gene in human lung cancer

Mitsuo Sato, Luc Girard, Ikuo Sekine, Noriaki Sunaga, Ruben D. Ramirez, Craig Kamibayashi, John D. Minna

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

The underlying molecular mechanisms leading to microsatellite alteration and mutations in human lung cancer remain unknown. Since Flap endonucleasel (Fen1), which functions in the base excision repair system, has been shown to be involved in tumor progression of mouse models with microsatellite instability in a haplo-insufficient manner, we performed expression and mutation analyses for FEN1 in human lung cancer cell lines. Reverse transcriptase PCR analysis revealed that all 49 lung cancer cell lines (20 small cell lung cancers (SCLCs) and 29 non-small cell lung cancers (NSCLCs)) expressed FEN1. In addition, microarray analysis showed that FEN1 expression was elevated significantly by 1.65-fold (P = 0.001) in SCLC cell lines compared to normal lung controls (normal human lung cultures and immortalized normal human bronchial epithelial cell lines). FEN1 protein was abundantly expressed in all 23 lung cancer cell lines (10 SCLCs and 13 NSCLCs) and was expressed at lower levels in three of four normal lung epithelial culture controls. Direct sequencing of genomic DNAs revealed no FEN1 mutation in seven SCLCs and nine NSCLCs. As part of this analysis we discovered and sequenced a FEN1 pseudogene (GenBank accession #AY249897) located at 1p22.2. This pseudogene is amplified from cDNA preparations contaminated with genomic DNA and must be taken into account in any FEN1 mutation analysis studies. Our results suggest that alterations of FEN1 are not likely to contribute to development of lung cancer.

Original languageEnglish (US)
Pages (from-to)7243-7246
Number of pages4
JournalOncogene
Volume22
Issue number46
DOIs
StatePublished - Oct 16 2003

Keywords

  • Base excision repair
  • Flap endonuclease 1 (FEN1)
  • Lung cancer
  • Microsatellite instability

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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