This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Franco, A. T. Articles by Peek, R. M. Search for Related Content PubMed PubMed Citation Articles by Franco, A. T. Articles by Peek, R. M., Jr. Related Collections Related Article

Regulation of Gastric Carcinogenesis by Helicobacter pylori Virulence Factors

¹ Division of Gastroenterology, Departments of Medicine and Cancer Biology and ² Department of Pathology, Vanderbilt University; ³ Department of Veterans Affairs Medical Center, Nashville, Tennessee; and ⁴ Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas

Requests for reprints: Richard M. Peek, Jr., Division of Gastroenterology, Vanderbilt University School of Medicine, 1030C MRB IV 2215B Garland Avenue, Nashville, TN 37232-2279. Phone: 615-322-5200; Fax: 615-343-6229; E-mail: richard.peek{at}vanderbilt.edu.

Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, and strains that possess the cag secretion system, which translocates the bacterial effector CagA into host cells, augment cancer risk. H. pylori strains that express the vacuolating cytotoxin or the outer membrane protein OipA are similarly associated with severe pathologic outcomes. We previously reported that an in vivo adapted H. pylori strain, 7.13, induces gastric adenocarcinoma in rodent models of gastritis. In the current study, we used carcinogenic strain 7.13 as a prototype to define the role of virulence constituents in H. pylori–mediated carcinogenesis. Mongolian gerbils were infected with wild-type strain 7.13 or cagA^–, vacA^–, or oipA^– mutants for 12 to 52 weeks. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals infected with the cagA^– but not the vacA^– or oipA^– strains. Gastric dysplasia and cancer developed in >50% of gerbils infected with either the wild-type or vacA^– strain but in none of the animals infected with the cagA^– strain. Inactivation of oipA decreased β-catenin nuclear localization in vitro and reduced the incidence of cancer in gerbils. OipA expression was detected significantly more frequently among H. pylori strains isolated from human subjects with gastric cancer precursor lesions versus persons with gastritis alone. These results indicate that loss of CagA prevents the development of cancer in this model. Inactivation of oipA attenuates β-catenin nuclear translocation and also decreases the incidence of carcinoma. In addition to defining factors that mediate H. pylori–induced cancer, these results provide insight into mechanisms that may regulate the development of other malignancies arising within the context of inflammatory states. [Cancer Res 2008;68(2):379–87]

Related Article

Comment re: Cancer Incidence Falls for Oldest

Charles Harding, Francesco Pompei, Ellen E. Lee, and Richard Wilson
Cancer Res. 2009 69: 379. [Full Text] [PDF]

This article has been cited by other articles:

				M.-R. KI, I.-H. HONG, J.-K. PARK, K.-S. HONG, O.-K. HWANG, J.-Y. HAN, A.-R. JI, S.-I. PARK, S.-K. LEE, S.-E. YOO, et al. Potent Neutralization of Vacuolating Cytotoxin (VacA) of Helicobacter pylori by Immunoglobulins Against the Soluble Recombinant VacA Anticancer Res, June 1, 2009; 29(6): 2393 - 2402. [Abstract] [Full Text] [PDF]

				D. M. Bronte-Tinkew, M. Terebiznik, A. Franco, M. Ang, D. Ahn, H. Mimuro, C. Sasakawa, M. J. Ropeleski, R. M. Peek Jr., and N. L. Jones Helicobacter pylori Cytotoxin-Associated Gene A Activates the Signal Transducer and Activator of Transcription 3 Pathway In vitro and In vivo Cancer Res., January 15, 2009; 69(2): 632 - 639. [Abstract] [Full Text] [PDF]

				O. Sokolova, P. M. Bozko, and M. Naumann Helicobacter pylori Suppresses Glycogen Synthase Kinase 3{beta} to Promote {beta}-Catenin Activity J. Biol. Chem., October 24, 2008; 283(43): 29367 - 29374. [Abstract] [Full Text] [PDF]

				D. P. O'Brien, J. Romero-Gallo, B. G. Schneider, R. Chaturvedi, A. Delgado, E. J. Harris, U. Krishna, S. R. Ogden, D. A. Israel, K. T. Wilson, et al. Regulation of the Helicobacter pylori Cellular Receptor Decay-accelerating Factor J. Biol. Chem., August 29, 2008; 283(35): 23922 - 23930. [Abstract] [Full Text] [PDF]

				R. M. Peek Jr Helicobacter pylori infection and disease: from humans to animal models Dis. Model. Mech., July 1, 2008; 1(1): 50 - 55. [Abstract] [Full Text] [PDF]

				R. M. Peek Jr Review: Prevention of gastric cancer: When is treatment of Helicobacter pylori warranted? Therapeutic Advances in Gastroenterology, July 1, 2008; 1(1): 19 - 31. [Abstract] [PDF]