title: Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic mice.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Jichi Medical School, Tochigi, Japan. muto@jichi.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mutoh
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakurai
authors.forename: Kiichi
authors.initials: K
authors.lastname: Satoh
authors.forename: Kiichi
authors.initials: K
authors.lastname: Tamada
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Sato
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Norio
authors.initials: N
authors.lastname: Isoda
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ido
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sugano
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology; D000818:Animals; D000071616:CDX2 Transcription Factor; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D017491:Genes, APC; D018398:Homeodomain Proteins / Q000502:physiology*; D008297:Male; D008679:Metaplasia; D051379:Mice; D008822:Mice, Transgenic; D013274:Stomach Neoplasms / Q000209:etiology*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53