title: Helicobacter pylori induces antiapoptosis through buclear factor-kappaB activation.
abstract: Although Helicobacter pylori is classified as a definite carcinogen, the mechanism underlying gastric carcinogenesis is not yet clear. We previously have shown that H. pylori activates an antiapoptotic gene, the cellular inhibitor of apoptosis protein 2 (c-IAP2), the underlying mechanism of which was investigated in the present study. cDNA array and real-time PCR analyses indicated that H. pylori showed a stimulatory effect on the expression of c-IAP2. Isogenic mutant strains with impaired cag pathogenicity island (cagPAI) expression showed weaker induction. Analyses that used the in situ terminal deoxynucleotide transferase-mediated dUTP nick end-labeling method indicated suppression of antiapoptosis by the antisense c-IAP2 oligonucleotide. Reporter assays with deletion and mutation constructs for the c-IAP2 promoter showed that nuclear factor-kappaB (NF-kappaB) binding sites are indispensable for transactivation. Super-repressor IkappaBalpha or NF-kappaB inhibitor reduced c-IAP2 transactivation by H. pylori, and exogenous expression of c-IAP2 inhibited apoptosis seen with H. pylori. In conclusion, H. pylori induces antiapoptosis through c-IAP2 transactivation following cagPAI-dependent NF-kappaB activation. The interaction of these stimuli may play a role in gastric carcinogenesis.
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan. ayanai-gi@umin.ac.jp.
authors.forename: Ayako
authors.initials: A
authors.lastname: Yanai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Mitsuno
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.forename: Wataru
authors.initials: W
authors.lastname: Shibata
authors.forename: Masao
authors.initials: M
authors.lastname: Akanuma
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Takao
authors.initials: T
authors.lastname: Kawabe
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D013274:Stomach Neoplasms / Q000473:pathology; D015533:Transcriptional Activation
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D011506:Proteins