RRC ID 42038
著者 Yanai A, Hirata Y, Mitsuno Y, Maeda S, Shibata W, Akanuma M, Yoshida H, Kawabe T, Omata M.
タイトル Helicobacter pylori induces antiapoptosis through buclear factor-kappaB activation.
ジャーナル J Infect Dis
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.
巻・号 188(11)
ページ 1741-51
公開日 2003-12-1
DOI 10.1086/379629
PII JID30721
PMID 14639546
MeSH Apoptosis* Cell Line, Tumor Helicobacter pylori / pathogenicity* Humans Inhibitor of Apoptosis Proteins NF-kappa B / physiology* Promoter Regions, Genetic Proteins / genetics Stomach Neoplasms / pathology Transcriptional Activation
IF 5.022
引用数 41
WOS 分野 INFECTIOUS DISEASES IMMUNOLOGY MICROBIOLOGY
リソース情報
ヒト・動物細胞 MKN45(RCB1001)