Published in:
01-05-2005 | Original Paper
New tumor necrosis factor-α-inducing protein released from Helicobacter pylori for gastric cancer progression
Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2005
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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-α (TNF-α)-inducing protein of H. pylori was studied.
Methods
The HP0596 gene of H. pylori was identified as the TNF-α-inducing protein (Tipα) gene from genome sequence of H. pylori strain 26695. Using recombinant Tipα (rTipα) and deleted Tipα (rdel-Tipα) proteins, the latter of which lacks six amino acids containing two cysteines in the N-terminal domain, we examined their activities in TNF-α gene expression and NF-κB 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
Tipα protein as a homodimer form (38 kDa) was found in both extracts and culture medium of various H. pylori strains. rTipα significantly induced TNF-α gene expression and NF-κB activation in both Bhas 42 cells and MGT-40, and induced in vitro transformation of Bhas 42 cells. However, rdel-Tipα did not. Treatment with MG-132, a proteasome inhibitor, inhibited translocation of NF-κB p65, and abrogated TNF-α induction induced by Tipα protein.
Conclusion
Tipα is a new carcinogenic factor released from H. pylori mediated through NF-κB activation.