title: Bile acid-induced expression of activation-induced cytidine deaminase during the development of Barrett's oesophageal adenocarcinoma.
abstract: Activation-induced cytidine deaminase (AID) induces somatic mutations in various host genes of non-lymphoid tissues, thereby contributing to carcinogenesis. We recently demonstrated that Helicobacter pylori infection and/or proinflammatory cytokine stimulation triggers aberrant AID expression in gastric epithelial cells, causing mutations in the tumour-suppressor TP53 gene. The findings of the present study provide evidence of ectopic AID expression in Barrett's oesophagus and Barrett's oesophageal adenocarcinoma, a cancer that develops under chronic inflammatory conditions. Immunoreactivity for endogenous AID was observed in 24 of 28 (85.7%) specimens of the columnar cell-lined Barrett's oesophagus and in 20 of 22 (90.9%) of Barrett's adenocarcinoma, whereas weak or no AID protein expression was detectable in normal squamous epithelial cells of the oesophagus. We validated these results by analysing tissue specimens from another cohort comprising 16 cases with Barrett's oesophagus and four cases with Barrett's adenocarcinoma. In vitro treatment of human non-neoplastic oesophageal squamous-derived cells with sodium salt deoxycholic acid induced ectopic AID expression via the nuclear factor-kappaB activation pathway. These findings suggest that aberrant AID expression occurs in a substantial proportion of Barrett's epithelium, at least in part due to bile acid stimulation. Considering the genotoxic activity of AID, our current findings suggest that aberrant AID expression might enhance the susceptibility to genetic alterations in Barrett's columnar-lined epithelial cells, leading to cancer development.
authors: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors: Shuko
authors: S
authors: Morita
authors: Yuko
authors: Y
authors: Matsumoto
authors: Shunsuke
authors: S
authors: Okuyama
authors: Koh
authors: K
authors: Ono
authors: Yoko
authors: Y
authors: Kitamura
authors: Akihisa
authors: A
authors: Tomori
authors: Tsuneo
authors: T
authors: Oyama
authors: Yuji
authors: Y
authors: Amano
authors: Yoshikazu
authors: Y
authors: Kinoshita
authors: Tsutomu
authors: T
authors: Chiba
authors: Hiroyuki
authors: H
authors: Marusawa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001647:Bile Acids and Salts; D016328:NF-kappa B; D012333:RNA, Messenger; D003840:Deoxycholic Acid; D003564:Cytidine Deaminase