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) |