title: Increased expression and no mutation of the Flap endonuclease (FEN1) gene in human lung cancer.
abstract: The underlying molecular mechanisms leading to microsatellite alteration and mutations in human lung cancer remain unknown. Since Flap endonuclease1 (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.
authors.affiliation: Department of Internal Medicine, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USA.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sato
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sunaga
authors.forename: Ruben D
authors.initials: RD
authors.lastname: Ramirez
authors.forename: Craig
authors.initials: C
authors.lastname: Kamibayashi
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000235:genetics; D002460:Cell Line; D002461:Cell Line, Transformed; D004260:DNA Repair / Q000235:genetics; D045585:Flap Endonucleases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D045585:Flap Endonucleases