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Article
Nature Medicine 13, 470 - 476 (2007)
Published online: 1 April 2007 | doi:10.1038/nm1566
Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium
Yuko Matsumoto1, Hiroyuki Marusawa1, Kazuo Kinoshita2, Yoko Endo1, Tadayuki Kou1, Toshiyuki Morisawa1, Takeshi Azuma3, Il-Mi Okazaki4, Tasuku Honjo4 & Tsutomu Chiba1
Abstract
Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the I
B kinase–dependent nuclear factor-B activation pathway. H. pylori–mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori–associated gastric carcinogenesis.
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