Journal Article

Bile acid-induced expression of activation-induced cytidine deaminase during the development of Barrett’s oesophageal adenocarcinoma

Shuko Morita, Yuko Matsumoto, Shunsuke Okuyama, Koh Ono, Yoko Kitamura, Akihisa Tomori, Tsuneo Oyama, Yuji Amano, Yoshikazu Kinoshita, Tsutomu Chiba and Hiroyuki Marusawa

in Carcinogenesis

Volume 32, issue 11, pages 1706-1712
Published in print November 2011 | ISSN: 0143-3334
Published online September 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr194
Bile acid-induced expression of activation-induced cytidine deaminase during the development of Barrett’s oesophageal adenocarcinoma

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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.

Journal Article.  4601 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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