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Generation of intestinal metaplasia by ectopic expression of Cdx1 and Cdx2

Research Project

Project/Area Number 13470122
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionJichi Medical School

Principal Investigator

SUGANO Kentaro  Jichi Med.Sch.Faculty Medicine Professor, 医学部, 教授 (60179116)

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)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2001: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordsintestinal metaplasia / transgenic mice / transcription factor / CDX1 / CDX2 / CDX
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.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Kentaro Sugano: "Grading gastritis ; an impossible dream?"Gastric Cancer. 5. 58-60 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Eda, K.Sugano et al.: "Expression of nomeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia"J.Gastroenterology. 37. 94-100 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Mutoh, K.Sugano et al.: "Conversion of gastric mucosa to intestinal metaplasia in Cdx2-expressing transgenic mice"Biochem.Biophy.Res.Commun.. 294. 470-479 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.satoh, K.Sugano et al.: "Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia"Helicobacter. 7.3. 192-198 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Eda, K.Sugano et al.: "Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa"J.Gastroenterology. 38. 14-22 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kentaro Sugano: "Grading gastritis : impossible dream?"Gastric Cancer. 5. 58-60 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akashi Eda, Hiroyuki Osawa, Ichiro Yanaka, Kiichi Satoh, Hiroyuki Mutoh, Ken Kihira, Kentaro Sugano: "Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia"J.Gastroenterology. 37. 94-100 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Mutoh, Y.Hakamata, K.Satoh, A.Eda, I.Yanaka, S.Honda, H.Osawa, Y.Kaneko, K.Sugano: "Conversion of Gastric mucosa to intestinal metaplasia in Cdx2-expressing transgenic mice"Biochem.Biophy.Res.Commun.. 294. 470-479 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Satoh, H.Mutoh, A.Eda, I.Yanaka, H.Osawa, S.Honda, H.Kawata, K.Kihira, K.Sugano: "Abberant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia ; effect of eradication of Helicobacter pylori"Helicobacter. 7. 192-198 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akashi Eda, Hiroyuki Osawa, Kiichi Satoh, Ichiro Yanaka, Ken Kihira, Yumiko Ishino, Hiroyuki Mutoh, Kentaro Sugano: "Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa"J.Gastroenterology. 38. 14-22 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kentaro Sugano: "Molecular Abnormalities in the Precancerous Conditions of the Stomach"Internal medicine. 42. 283-284 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroyki Mutoh, Shinji Sakurai, Kiichi Satoh, Yoji Hakamata, Kentaro Sugano: "Cdx1-induced intestinal metaplasia in the transgenic mouse stomach"(submitting).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kentaro Sugano: "Grading gastritis ; an impossible dream?"Gastric Cancer. 5. 58-60 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Eda, K.Sugano et al.: "Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia"J. Gastroenterlogy. 37. 94-100 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Mutoh, K.sugano, et al.: "Coversion of gastric mucosa to intestinal metaplasia in Cdx2-expressing transgenic mice"Biochem. Biophy. Res. Commun.. 294・2. 470-479 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Satoh, K.Sugano et al.: "Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia ; effect of infection..."Helicobacter. 7・3. 192-198 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Eda, K.Sugano et al.: "Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa"J. Gastroentrology. 38. 14-22 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Eda, H.Osawa, K.Sugano: "Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia"J.Gastroenterology. 37・2. 94-100 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Satoh K, Mutoh H, Sugano K: "Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia"Helicobacter. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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