Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium.
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 IkappaB kinase-dependent nuclear factor-kappaB 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.
Matsumoto
Yuko
Y
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Marusawa
Hiroyuki
H
Kinoshita
Kazuo
K
Endo
Yoko
Y
Kou
Tadayuki
T
Morisawa
Toshiyuki
T
Azuma
Takeshi
T
Okazaki
Il-Mi
IM
Honjo
Tasuku
T
Chiba
Tsutomu
T
D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D003564:Cytidine Deaminase / Q000378:metabolism*; D017931:DNA Primers; D005753:Gastric Mucosa / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008954:Models, Biological; D016296:Mutagenesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D017931:DNA Primers; D016328:NF-kappa B; C080866:cagA protein, Helicobacter pylori; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase