This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Fox, J. G. Articles by Wang, T. C. Search for Related Content PubMed PubMed Citation Articles by Fox, J. G. Articles by Wang, T. C.

(American Journal of Pathology. 2007;171:1520-1528.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070249

Accelerated Progression of Gastritis to Dysplasia in the Pyloric Antrum of TFF2^–/– C57BL6 x Sv129 Helicobacter pylori-Infected Mice

James G. Fox^*, Arlin B. Rogers^*, Mark T. Whary^*, Zhongming Ge^*, Masa Ohtani^*, Evelyn Kurt Jones and Timothy C. Wang

From the Division of Comparative Medicine,^* Massachusetts Institute of Technology, Cambridge, Massachusetts; the University of Massachusetts Medical Center, Worcester, Massachusetts; and Columbia University, New York, New York

Trefoil factor family 2 (TFF2) is up-regulated in Helicobacter spp.-infected gastric tissues of both humans and mice. To ascertain the biological effects of TFF2 in vivo, TFF2^–/– C57BL/6 x Sv129 and wild-type (WT) C57BL/6 x Sv129 mice were orally infected with Helicobacter pylori SS1. Mice were evaluated for gastric H. pylori colonization, pathology, and cytokine profiles at 6 and 19 months post inoculation (pi). At 6 months pi, there was a significant difference (P < 0.05) for epithelial criteria (mucosal defects, atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia) in the corpus of TFF2^–/– versus WT mice. At 19 months pi, a similar statistical difference in epithelial parameters was noted in the antrum of TFF2^–/– versus WT mice (P < 0.01). All of the TFF2^–/– H. pylori-infected mice had high-grade antral dysplasia, including gastric intraepithelial neoplasia, which was statistically significant (P < 0.05) compared with the infected WT mice. Levels of interferon- were markedly elevated in the gastric mucosa of infected TFF2^–/– mice at both 6 and 19 months pi. TFF2 provided a cytoprotective and/or anti-inflammatory effect against the progression of premalignant lesions of the gastric corpus at 6 months pi and in the pyloric antrum in H. pylori-infected mice at 19 months pi. These data support a protective role for TFF2 in part by modulating levels of gastric interferon- in the development of H. pylori-associated premalignancy of the distal stomach.

This article has been cited by other articles:

				S. P. Tu, A. L. Chi, W. Ai, S. Takaishi, Z. Dubeykovskaya, M. Quante, J. G. Fox, and T. C. Wang p53 inhibition of AP1-dependent TFF2 expression induces apoptosis and inhibits cell migration in gastric cancer cells Am J Physiol Gastrointest Liver Physiol, August 1, 2009; 297(2): G385 - G396. [Abstract] [Full Text] [PDF]

				S. Takaishi, S. Tu, Z. A. Dubeykovskaya, M. T. Whary, S. Muthupalani, B. H. Rickman, A. B. Rogers, N. Lertkowit, A. Varro, J. G. Fox, et al. Gastrin Is an Essential Cofactor for Helicobacter-Associated Gastric Corpus Carcinogenesis in C57BL/6 Mice Am. J. Pathol., July 1, 2009; 175(1): 365 - 375. [Abstract] [Full Text] [PDF]

				L. B. Lemke, Z. Ge, M. T. Whary, Y. Feng, A. B. Rogers, S. Muthupalani, and J. G. Fox Concurrent Helicobacter bilis Infection in C57BL/6 Mice Attenuates Proinflammatory H. pylori-Induced Gastric Pathology Infect. Immun., May 1, 2009; 77(5): 2147 - 2158. [Abstract] [Full Text] [PDF]

				Z. Dubeykovskaya, A. Dubeykovskiy, J. Solal-Cohen, and T. C. Wang Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines J. Biol. Chem., February 6, 2009; 284(6): 3650 - 3662. [Abstract] [Full Text] [PDF]

				C.-W. Lee, B. Rickman, A. B. Rogers, Z. Ge, T. C. Wang, and J. G. Fox Helicobacter pylori Eradication Prevents Progression of Gastric Cancer in Hypergastrinemic INS-GAS Mice Cancer Res., May 1, 2008; 68(9): 3540 - 3548. [Abstract] [Full Text] [PDF]