2002 Fiscal Year Final Research Report Summary
Generation of intestinal metaplasia by ectopic expression of Cdx1 and Cdx2
| Project/Area Number |
13470122
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
SUGANO Kentaro Jichi Med.Sch.Faculty Medicine Professor, 医学部, 教授 (60179116)
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| Co-Investigator(Kenkyū-buntansha) |
OSAWA Hiroyuki Jichi Med.Sch.Faculty Medicine Assistant Lecturer, 医学部, 助手 (70260833)
SATOH Kiichi Jichi Med.Sch.Faculty Medicine Senior Lecturer, 医学部, 講師 (50275707)
MUTO Hiroyuki Jichi Med.Sch.Faculty Medicine Senior Lecturer, 医学部, 講師 (50322392)
KUMAKURA Yasuhisa Jichi Med.Sch.Faculty Medicine Assistant Lecturer (50275682)
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| Project Period (FY) |
2001 – 2002
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| Keywords | intestinal metaplasia / transgenic mice / transcription factor / CDX1 / CDX2 |
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| Research Abstract |
In an attempt to elucidate the mechanism of transdifferentiation of gastric and esophageal mucosa to intestinal metaplasia that is considered to be a precancerous state, we have generated mice models expressing either Cdx-1 or Cdx-2 homeobox gene in the parietal cells. In the Cdx-lexpressing mice, gastric fundic mucosa was gradually converted to intestinal mucosa with absorptive, goblet, entero-endocrine and Paneth cell lineage. By contrast, intestinal metaplasia developed by Cdx-2 expression in the gastric mucosa exhibit absorptive, goblet and entero-endocrine cells but lacked Paneth cell lineage. The intestinal metaplasia of these two mice models differs in terms of mucosal architecture. The regular and orderly architecture of intestinal pit to villus was lost and Paneth cells were dispersed in the tip portion of the villi in the Cdx-1 transgenic mice. In Cdx-2 mice, the psuedopyloric gland like portion was found in the base of the gland similar to the incomplete intestinal metaplasia. In both mice models, mucosal proliferation was accelerated resulting in hyperplasia and polyp-like formation was noted at the later stage. We are currently analyzing the alteration of the gene expression induced by the ectopic expression of Cdx-1 and Cdx-2. In human gastric and esophageal mucosa, we have confirmed that Cdx-2 expression precedes the phenotypic change to intestinal metaplasia, implicating its role as a trigger.
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