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 Mutoh, H. Articles by Sugano, K. Search for Related Content PubMed PubMed Citation Articles by Mutoh, H. Articles by Sugano, K.

Development of Gastric Carcinoma from Intestinal Metaplasia in Cdx2-transgenic Mice

Departments of ¹ Gastroenterology and ² Pathology, Jichi Medical School, Tochigi, Japan

In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Many epidemiologic studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence that shows intestinal metaplasia is a precursor lesion of gastric carcinoma, to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma that invaded the submucosa and muscularis propria and occasionally spread into the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas. The participation of APC and p53 gene mutations in gastric carcinogenesis from the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying Apc^Min mutation or p53 deficiency, that developed gastric polyps much earlier than Cdx2 alone. We successfully showed that long-term intestinal metaplasia induces invasive gastric carcinoma. These results indicate that intestinal metaplasia itself plays a significant role in the genesis and progression of gastric carcinoma.

This article has been cited by other articles:

				H. Tomita, Y. Yamada, T. Oyama, K. Hata, Y. Hirose, A. Hara, T. Kunisada, Y. Sugiyama, Y. Adachi, H. Linhart, et al. Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the {beta}-Catenin/Tcf Signaling Pathway Cancer Res., May 1, 2007; 67(9): 4079 - 4087. [Abstract] [Full Text] [PDF]

				T. Liu, X. Zhang, C.-K. So, S. Wang, P. Wang, L. Yan, R. Myers, Z. Chen, A. P. Patterson, C. S. Yang, et al. Regulation of Cdx2 expression by promoter methylation, and effects of Cdx2 transfection on morphology and gene expression of human esophageal epithelial cells Carcinogenesis, February 1, 2007; 28(2): 488 - 496. [Abstract] [Full Text] [PDF]

				C. A Rubio My approach to reporting a gastric biopsy J. Clin. Pathol., February 1, 2007; 60(2): 160 - 166. [Abstract] [Full Text] [PDF]

				M. E. Witek, K. Nielsen, R. Walters, T. Hyslop, J. Palazzo, S. Schulz, and S. A. Waldman The Putative Tumor Suppressor Cdx2 Is Overexpressed by Human Colorectal Adenocarcinomas Clin. Cancer Res., December 15, 2005; 11(24): 8549 - 8556. [Abstract] [Full Text] [PDF]

				Z. Fan, J. Li, B. Dong, and X. Huang Expression of Cdx2 and Hepatocyte Antigen in Gastric Carcinoma: Correlation with Histologic Type and Implications for Prognosis Clin. Cancer Res., September 1, 2005; 11(17): 6162 - 6170. [Abstract] [Full Text] [PDF]