New tumor necrosis factor-alpha-inducing protein released from Helicobacter pylori for gastric cancer progression.
OBJECTIVE
To investigate the association between Helicobacter pylori infection and its inflammatory reaction in gastritis, gastric ulcer, and gastric cancer, a new tumor necrosis factor-alpha (TNF-alpha)-inducing protein of H. pylori was studied.


METHODS
The HP0596 gene of H. pylori was identified as the TNF-alpha-inducing protein (Tipalpha) gene from genome sequence of H. pylori strain 26695. Using recombinant Tipalpha (rTipalpha) and deleted Tipalpha (rdel-Tipalpha) proteins, the latter of which lacks six amino acids containing two cysteines in the N-terminal domain, we examined their activities in TNF-alpha gene expression and NF-kappaB activation in both Bhas 42 (v-H-ras transfected BALB/3T3) cells and mouse gastric epithelial cell line MGT-40, and in vitro transformation of Bhas 42 cells.


RESULTS
Tipalpha protein as a homodimer form (38 kDa) was found in both extracts and culture medium of various H. pylori strains. rTipalpha significantly induced TNF-alpha gene expression and NF-kappaB activation in both Bhas 42 cells and MGT-40, and induced in vitro transformation of Bhas 42 cells. However, rdel-Tipalpha did not. Treatment with MG-132, a proteasome inhibitor, inhibited translocation of NF-kappaB p65, and abrogated TNF-alpha induction induced by Tipalpha protein.


CONCLUSIONS
Tipalpha is a new carcinogenic factor released from H. pylori mediated through NF-kappaB activation.
Suganuma
Masami
M
Saitama Cancer Center, Ina Kitaadachi-gun, 362-0806 Saitama, Japan. masami@cancer-c.pref.saitama.jp
Kurusu
Miki
M
Suzuki
Kaori
K
Nishizono
Akira
A
Murakami
Kazunori
K
Fujioka
Toshio
T
Fujiki
Hirota
H
D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000378:metabolism*; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D018450:Disease Progression; D016480:Helicobacter pylori; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000032:analysis; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology*; D014162:Transfection
D001426:Bacterial Proteins; D014408:Biomarkers, Tumor; D016328:NF-kappa B; C505332:Tipalpha protein, Helicobacter pylori