This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hirata, Y.
Right arrow Articles by Omata, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hirata, Y.
Right arrow Articles by Omata, M.

 Previous Article  |  Next Article 

Infection and Immunity, June 2001, p. 3965-3971, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3965-3971.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Helicobacter pylori Activates the Cyclin D1 Gene through Mitogen- Activated Protein Kinase Pathway in Gastric Cancer Cells

Yoshihiro Hirata,* Shin Maeda, Yuzo Mitsuno, Masao Akanuma, Yutaka Yamaji, Keiji Ogura, Haruhiko Yoshida, Yasushi Shiratori, and Masao Omata

Department of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

Received 27 November 2000/Returned for modification 2 February 2001/Accepted 26 March 2001

Helicobacter pylori induces cellular proliferation in host cells, but the mechanism remains unclear. Thus, we examined the effect of H. pylori on cyclin D1, an important regulator of the cell cycle, especially in relation to intracellular signaling pathways. In a Northern blot analysis, cyclin D1 transcription in gastric cancer (AGS) cells was enhanced by coculture with H. pylori strain TN2 in a time-dependent and multiplicity-of-infection-dependent manner. An isogenic mutant form of vacA also increased cyclin D1 transcription, but mutant forms of cagE or the entire cag pathogenicity island did not enhance cyclin D1 transcription. These effects were confirmed with a luciferase assay of the cyclin D1 promoter (pD1luc). Cyclin D1 promoter activation by H. pylori was inhibited by MEK inhibitors (U0126 and PD98059), indicating that the mitogen-activated protein kinase pathway may be involved in intracellular signal transduction. In contrast, transfection of a reporter plasmid having any point mutations of the NF-kappa B binding sites in the promoter (pD1-kappa B1M, pD1-kappa B2M, or pD1-kappa B1/2M) or cotransfection of dominant negative Ikappa Balpha did not affect cyclin D1 activation by H. pylori. In conclusion, H. pylori activates cyclin D1 through the mitogen-activated protein kinase pathway and not through NF-kappa B activation in AGS cells. This activation of cyclin D1 is partly dependent on the cag pathogenicity island but not on vacA.

* Corresponding author. Mailing address: Department of Gastroenterology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Phone: 3-3815-5411, ext. 33056. Fax: 3-3814-0021. E-mail: HIRATAY-INT{at}h.u-tokyo.ac.jp.

Infection and Immunity, June 2001, p. 3965-3971, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3965-3971.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ogden, S. R., Wroblewski, L. E., Weydig, C., Romero-Gallo, J., O'Brien, D. P., Israel, D. A., Krishna, U. S., Fingleton, B., Reynolds, A. B., Wessler, S., Peek, R. M. Jr (2008). p120 and Kaiso Regulate Helicobacter pylori-induced Expression of Matrix Metalloproteinase-7. Mol. Biol. Cell 19: 4110-4121 [Abstract] [Full Text]  
  • Snider, J. L., Allison, C., Bellaire, B. H., Ferrero, R. L., Cardelli, J. A. (2008). The {beta}1 Integrin Activates JNK Independent of CagA, and JNK Activation Is Required for Helicobacter pylori CagA+-induced Motility of Gastric Cancer Cells. J. Biol. Chem. 283: 13952-13963 [Abstract] [Full Text]  
  • Bebb, J R, Leach, L, Zaitoun, A, Hand, N, Letley, D P, Thomas, R, Atherton, J C (2006). Effects of Helicobacter pylori on the cadherin-catenin complex. J. Clin. Pathol. 59: 1261-1266 [Abstract] [Full Text]  
  • Lin, Y.-F., Wu, M.-S., Chang, C.-C., Lin, S.-W., Lin, J.-T., Sun, Y.-J., Chen, D.-S., Chow, L.-P. (2006). Comparative Immunoproteomics of Identification and Characterization of Virulence Factors from Helicobacter pylori Related to Gastric Cancer. Mol. Cell. Proteomics 5: 1484-1496 [Abstract] [Full Text]  
  • Hirata, Y., Maeda, S., Ohmae, T., Shibata, W., Yanai, A., Ogura, K., Yoshida, H., Kawabe, T., Omata, M. (2006). Helicobacter pylori Induces I{kappa}B Kinase {alpha} Nuclear Translocation and Chemokine Production in Gastric Epithelial Cells. Infect. Immun. 74: 1452-1461 [Abstract] [Full Text]  
  • Biarc, J., Nguyen, I. S., Pini, A., Gosse, F., Richert, S., Thierse, D., Van Dorsselaer, A., Leize-Wagner, E., Raul, F., Klein, J.-P., Scholler-Guinard, M. (2004). Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S.bovis). Carcinogenesis 25: 1477-1484 [Abstract] [Full Text]  
  • Trudgill, N J, Suvarna, S K, Royds, J A, Riley, S A (2003). Cell cycle regulation in patients with intestinal metaplasia at the gastro-oesophageal junction. Mol. Pathol. 56: 313-317 [Abstract] [Full Text]  
  • De Luca, A., Baldi, A., Russo, P., Todisco, A., Altucci, L., Giardullo, N., Pasquale, L., Iaquinto, S., D'Onofrio, V., Parodi, M. C., Paggi, M. G., Iaquinto, G. (2003). Coexpression of Helicobacter Pylori's Proteins CagA and HspB Induces Cell Proliferation in AGS Gastric Epithelial Cells, Independently from the Bacterial Infection. Cancer Res. 63: 6350-6356 [Abstract] [Full Text]  
  • Choi, I. J., Kim, J. S., Kim, J. M., Jung, H. C., Song, I. S. (2003). Effect of Inhibition of Extracellular Signal-Regulated Kinase 1 and 2 Pathway on Apoptosis and bcl-2 Expression in Helicobacter pylori-Infected AGS Cells. Infect. Immun. 71: 830-837 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»