title: Aberrant expression and mutation-inducing activity of AID in human lung cancer.
abstract: BACKGROUND
  Activation-induced cytidine deaminase (AID) is expressed in B lymphocytes and triggers antibody diversification. Recent reports have indicated that the constitutive expression of AID in mice causes not only lymphomas, but also cancers of some organs including the lung, prompting us to investigate the expression and effect of AID on human lung cancer.
  
  
  METHODS
  We examined AID mRNA expression in 17 lung cancer cell lines and 51 primary lung cancers using a quantitative RT-PCR analysis. Next, we established H1299 lung cancer cells stably overexpressing AID and performed a supF forward mutation assay. We then examined AID protein expression and p53 mutation in 129 primary lung cancers by an immunohistochemical analysis and PCR-SSCP and sequencing analyses, respectively.
  
  
  RESULTS
  Aberrant mRNA expression of AID was detected in 29% (5 of 17) of the lung cancer cell lines and 31% (16 of 51) of the primary lung cancers. AID-overexpressing H1299 clones showed a 5.0- to 6.1-fold higher mutation frequency than an empty vector-transfected H1299 clone, and about half of the AID-induced mutations were base substitutions, indicating that AID induces gene mutations in lung cancer cells. Furthermore, an association was found between the AID protein expression level and the p53 mutation status in an analysis of 129 primary lung cancers. A further expression analysis revealed that a portion of AID is localized at the centrosomes.
  
  
  CONCLUSIONS
  Our current findings suggest that the aberrant expression of AID may be involved in a subset of human lung cancers as a result of its mutation-inducing activity.
authors.affiliation: Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan. kzshinmu@hama-med.ac.jp
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Hisaki
authors.initials: H
authors.lastname: Igarashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Goto
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamada
authors.forename: Shun
authors.initials: S
authors.lastname: Matsuura
authors.forename: Mari
authors.initials: M
authors.lastname: Tajima
authors.forename: Tomonari
authors.initials: T
authors.lastname: Matsuda
authors.forename: Arito
authors.initials: A
authors.lastname: Yamane
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Funai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tanahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Niwa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogawa
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D016153:Genes, Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000166:cytology / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009152:Mutagenicity Tests; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C096275:supF tRNA; D012343:RNA, Transfer; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase