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

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Abstract

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.

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Acknowledgements

Supported by the following Grants-in-Aid: Scientific Research on Priority Areas for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Smoking Research Fund. We thank Ms Ikuko Shiotani, Saitama Cancer Center, for her assistance and Ms Maki Kimoto, Oita Medical University, for technical assistance in bacterial cultures. We also thank Drs Masae Tatematsu and Chihiro Sasakawa for the supply of MGT-40 cells and H. pylori strain 26695 and 26695ΔcagPΑΙ.

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Authors and Affiliations

  1. Saitama Cancer Center, Ina Kitaadachi-gun, 362-0806, Saitama, Japan

    Masami Suganuma, Miki Kurusu & Kaori Suzuki

  2. Oita Medical University, Oita, Japan

    Akira Nishizono, Kazunori Murakami & Toshio Fujioka

  3. Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Tokushima, Japan

    Hirota Fujiki

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  1. Masami Suganuma
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  2. Miki Kurusu
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  3. Kaori Suzuki
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  4. Akira Nishizono
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  5. Kazunori Murakami
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  7. Hirota Fujiki
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Correspondence to Masami Suganuma.

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Suganuma, M., Kurusu, M., Suzuki, K. et al. New tumor necrosis factor-α-inducing protein released from Helicobacter pylori for gastric cancer progression. J Cancer Res Clin Oncol 131, 305–313 (2005). https://doi.org/10.1007/s00432-004-0652-x

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  • DOI: https://doi.org/10.1007/s00432-004-0652-x

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