| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics, Preclinical Pharmacology |
Dipartimento di Internistica Clinica e Sperimentale-Cattedra di Gastroenterologia, Seconda Università di Napoli, Napoli [C. T., B. A. M., C. D. V. B., M. R.]; Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, 80131 Napoli [R. C., G. T., F. C.]; Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università Federico II, Napoli [R. Z.]; and Istituto di Fisiologia Umana, Università di Pavia [V. R.], Italy
Purpose: Helicobacter pylori causes gastric damage and is involved in gastric carcinogenesis. Vascular endothelial growth factor (VEGF) plays a major role in gastric mucosa repair and is overexpressed in gastric cancer. We investigated: (a) whether H. pylori, and in particular H. pylori VacA toxin, affected VEGF expression in gastric epithelial cells in culture; and (b) the signal transduction pathway involved in any effect exerted by H. pylori.
Experimental Design: MKN-28 cells were incubated with uninoculated BCF (control) or with BCF obtained from VacA-producing wild-type H. pylori 60190 strain or from its isogenic mutant 60190:v1, specifically lacking vacA gene in the presence or absence of ZD 1839, a selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, PD098059, a selective inhibitor of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase, the kinase responsible for ERK phosphorylation, or SC-236, a selective inhibitor of cyclooxygenase (COX)-2 for 24–48 h.
Results: (a) Toxigenic H. pylori up-regulated VEGF mRNA and protein expression and caused a 2.5-fold increase in VEGF release compared with control, whereas nontoxigenic H. pylori did not; (b) H. pylori VacA toxin-induced up-regulation of VEGF was counteracted by selective inhibition of EGFR tyrosine kinase; (c) toxigenic H. pylori activated the ERK/MAP kinase cascade, and inhibition of MAP kinase activation counteracted H. pylori-induced VEGF up-regulation; (d) toxigenic H. pylori up-regulated COX-2 expression, and this effect was counteracted by blockade of EGFR tyrosine kinase; and (e) COX-2 selective inhibition counteracted H. pylori-induced up-regulation of VEGF.
Conclusion: (a) H. pylori up-regulates VEGF expression in gastric epithelial cells; and (b) this effect is specifically related to VacA toxin and seems to depend on the activation of an EGFR-, MAP kinase-, and COX-2-mediated pathway.
This article has been cited by other articles:
|
|
 |
|
  M.-R. Ki, H.-R. Lee, M.-J. Goo, I.-H. Hong, S.-H. Do, D.-H. Jeong, H.-J. Yang, D.-W. Yuan, J.-K. Park, and K.-S. Jeong Differential regulation of ERK1/2 and p38 MAP kinases in VacA-induced apoptosis of gastric epithelial cells Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G635 - G647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hisatsune, E. Yamasaki, M. Nakayama, D. Shirasaka, H. Kurazono, Y. Katagata, H. Inoue, J. Han, J. Sap, K. Yahiro, et al. Helicobacter pylori VacA Enhances Prostaglandin E2 Production through Induction of Cyclooxygenase 2 Expression via a p38 Mitogen-Activated Protein Kinase/Activating Transcription Factor 2 Cascade in AZ-521 Cells Infect. Immun., September 1, 2007; 75(9): 4472 - 4481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Yeo, D-K Kim, S U Han, J E Lee, Y B Kim, Y K Cho, J H Kim, S W Cho, and K-B Hahm Novel action of gastric proton pump inhibitor on suppression of Helicobacter pylori induced angiogenesis Gut, January 1, 2006; 55(1): 26 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Y. Shin, W. K.K. Wu, Y.-N. Ye, W. H.L. So, M. W.L. Koo, E. S.L. Liu, J.-C. Luo, and C.-H. Cho Nicotine promotes gastric tumor growth and neovascularization by activating extracellular signal-regulated kinase and cyclooxygenase-2 Carcinogenesis, December 1, 2004; 25(12): 2487 - 2495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Chang, M. S. Wu, J. T. Lin, B. S. Sheu, T. Muta, H. Inoue, and C.-C. Chen Induction of Cyclooxygenase-2 Overexpression in Human Gastric Epithelial Cells by Helicobacter pylori Involves TLR2/TLR9 and c-Src-Dependent Nuclear Factor-{kappa}B Activation Mol. Pharmacol., December 1, 2004; 66(6): 1465 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Preusch, A. J. Grau, F. Buggle, C. Lichy, J. Bartel, C. Black, and J. Rudi Association Between Cerebral Ischemia and Cytotoxin-Associated Gene-A-Bearing Strains of Helicobacter pylori Stroke, August 1, 2004; 35(8): 1800 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Yao, L. Wang, D. Wei, W. Gong, M. Hassan, T.-T. Wu, P. Mansfield, J. Ajani, and K. Xie Association between Expression of Transcription Factor Sp1 and Increased Vascular Endothelial Growth Factor Expression, Advanced Stage, and Poor Survival in Patients with Resected Gastric Cancer Clin. Cancer Res., June 15, 2004; 10(12): 4109 - 4117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nakayama, M. Kimura, A. Wada, K. Yahiro, K.-i. Ogushi, T. Niidome, A. Fujikawa, D. Shirasaka, N. Aoyama, H. Kurazono, et al. Helicobacter pylori VacA Activates the p38/Activating Transcription Factor 2-mediated Signal Pathway in AZ-521 Cells J. Biol. Chem., February 20, 2004; 279(8): 7024 - 7028. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
