Carcinogenic role of tumor necrosis factor-alpha inducing protein of Helicobacter pylori in human stomach.
Helicobacter pylori is the definitive carcinogen for stomach cancer and is known to induce proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1(IL-1) in the stomach. Based on our findings that TNF-alpha is an endogenous tumor promoter, we identified the TNFalpha inducing protein (Tipalpha) gene family, and confirmed Tipalpha and HP-MP1 as new carcinogenic proteins of H. pylori.Tipalpha protein is unique to H. pylori, and this paper shows the strong tumor promoting activity of Tipalpha gene family, in cooperation with Ras protein and its mechanisms of action in relation to NF-kappaB activation, and discusses the carcinogenic role of Tipalpha in stomach cancer. Our recent finding showing that penicillin-binding proteins of other bacteria are weak homologues of Tipalpha is also discussed.
Suganuma
Masami
M
Saitama Cancer Center, Research Institute for Clinical Oncology, Saitama 362-0806, Japan. masami@cancer-c.pref.saitama.jp
Kuzuhara
Takashi
T
Yamaguchi
Kensei
K
Fujiki
Hirota
H
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D019281:Dimerization; D016481:Helicobacter Infections; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism; D046915:Penicillin-Binding Proteins / Q000737:chemistry; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013270:Stomach / Q000382:microbiology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
D001426:Bacterial Proteins; D016328:NF-kappa B; D046915:Penicillin-Binding Proteins; C505332:Tipalpha protein, Helicobacter pylori; D014409:Tumor Necrosis Factor-alpha; D018631:ras Proteins