Journal
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 131, Issue 5, Pages 305-313Publisher
SPRINGER
DOI: 10.1007/s00432-004-0652-x
Keywords
stomach cancer; NF-kappa B; I kappa B; transformation
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Purpose: 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 (Tip alpha) gene from genome sequence of H. pylori strain 26695. Using recombinant Tip alpha (rTip alpha) and deleted Tip alpha (rdel-Tip alpha) 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-kappa B activation in both Bhas 42 (v-Hras transfected BALB/3T3) cells and mouse gastric epithelial cell line MGT-40, and in vitro transformation of Bhas 42 cells. Results: Tipa protein as a homodimer form ( 38 kDa) was found in both extracts and culture medium of various H. pylori strains. rTipa significantly induced TNF-alpha gene expression and NF-kappa B activation in both Bhas 42 cells and MGT-40, and induced in vitro transformation of Bhas 42 cells. However, rdel-Tip alpha did not. Treatment with MG-132, a proteasome inhibitor, inhibited translocation of NF-kappa B p65, and abrogated TNF-alpha induction induced by Tipa protein. Conclusion: Tipa is a new carcinogenic factor released from H. pylori mediated through NF-kappa B activation.
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