| Project/Area Number |
16590622
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | JICHI MEDICAL SCHOOL |
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Principal Investigator |
SATOH Kiichi JICHI MEDICAL SCHOOL, School of Medicine, Senior Lecturer, 医学部, 講師 (50275707)
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| Co-Investigator(Kenkyū-buntansha) |
SUGANO Kentaro JICHI MEDICAL SCHOOL, School of Medicine, Professor, 医学部, 教授 (60179116)
MUTOH Hiroyuki JICHI MEDICAL SCHOOL, School of Medicine, Senior Lecturer, 医学部, 講師 (50322392)
OSAWA Hiroyuki JICHI MEDICAL SCHOOL, School of Medicine, Assistant Lecturer, 医学部, 助手 (70260833)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | intestinal metaplasia / gastric carcinoma / transcription factor / Cdx2 / transgenic mouse |
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| Research Abstract |
In the progression of chronic gastritis, gastric inucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Gastric intestinal metaplasia occurs as a pathological condition in the gastric mucosa. The intestine-specific transcription factor Cdx2 is expressed in the human gastric intestinal metaplastic mucosa. We established Cdx2-transgenic mice expressing transcription factor Cdx2 in the gastric mucosa. The gastric fundic mucosa of the Cdx2-transgenic mice was completely changed into intestinal metaplastic mucosa.
Many epidemiological studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence which shows intestinal metaplasia is a precursor lesion of gastric carcinoma to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice. 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 demonstrated 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.
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