New tumor necrosis factor-?-inducing protein released from Helicobacter pylori for gastric cancer progression

• Published in: Journal of cancer research and clinical oncology 2005-05, Vol.131 (5), p.305-313
• Main Authors: Suganuma, Masami, Kurusu, Miki, Suzuki, Kaori, Nishizono, Akira, Murakami, Kazunori, Fujioka, Toshio, Fujiki, Hirota
• Format: Article
• Language: English
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-004-0652-x

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. 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. 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. Tipalpha is a new carcinogenic factor released from H. pylori mediated through NF-kappaB activation.