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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.
AuthorsShuko Morita, Yuko Matsumoto, Shunsuke Okuyama, Koh Ono, Yoko Kitamura, Akihisa Tomori, Tsuneo Oyama, Yuji Amano, Yoshikazu Kinoshita, Tsutomu Chiba, Hiroyuki Marusawa
JournalCarcinogenesis (Carcinogenesis) Vol. 32 Issue 11 Pg. 1706-12 (Nov 2011) ISSN: 1460-2180 [Electronic] England
PMID21890457 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bile Acids and Salts
  • NF-kappa B
  • RNA, Messenger
  • Deoxycholic Acid
  • Cytidine Deaminase
Topics
  • Adenocarcinoma (drug therapy, metabolism, pathology)
  • Adult
  • Aged
  • Aged, 80 and over
  • Barrett Esophagus (drug therapy, metabolism, pathology)
  • Bile Acids and Salts (pharmacology)
  • Blotting, Western
  • Cells, Cultured
  • Cytidine Deaminase (genetics, metabolism)
  • Deoxycholic Acid (pharmacology)
  • Esophageal Neoplasms (drug therapy, metabolism, pathology)
  • Esophagus (drug effects, metabolism, pathology)
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • NF-kappa B (genetics, metabolism)
  • RNA, Messenger (genetics)
  • Real-Time Polymerase Chain Reaction

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