Transcriptional regulation of transcription factor Cdx2 in intestinal mucosa

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Jichi Medical School
• Principal Investigator: MUTOH Hiroyuki Jichi Medical School, Internal Medicine, Instructor, 医学部, 講師 (50322392)
• Co-Investigator(Kenkyū-buntansha): SATOH Kiichi Jichi Medical School, Internal Medicine, Instructor, 医学部, 講師 (50275707) ; SUGANO Kentaro Jichi Medical School, Internal Medicine, Professor, 医学部, 教授 (60179116)
• Project Period (FY): 2002 – 2003
• Keywords: Cdx2 / Intestinal metaplasia / Transgenic mouse / Absorptive enterocytes / PCFS / Math1 / Enteroendocrine cells / Stroma

Research Abstract

In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. 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 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 ApcMin 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.

Research Products

• [Publications] Ratineau C, Petry MW, Mutoh H, Leiter AB: "Cyclin D1 represses the basic helix loop helix transcription factor, BETA2/NeuroD"J.Biol.Chem.. 277. 8847-8853 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Eda A, Osawa H, Yanaka I, Satoh K, Mutoh H, Kihira K, Sugano K: "Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia"J.Gastroenterol.. 37. 94-100 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Satoh K, Mutoh H, Eda A, Yanaka I, Osawa H, Honda S, Kawata H, Kihira K, Sugano K: "Aberrant 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(和文)」より
• [Publications] Mutoh H, Hakamata Y, Sato K, Eda A, Yanaka I, Honda S, Osawa H, Kaneko Y, Sugano K: "Conversion of gastric mucosa to intestinal metaplasia in Cdx2-expressing transgenic mice"Biochem.Biophys.Res.Commun.. 294. 470-479 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Eda A, Osawa H, Satoh K, Yanaaka I, Kihira K, Ishino Y, Mutoh H, Sugano K: "Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa"J.Gastroenterol.. 38. 14-22 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Satoh K, Kawata H, Tokumaru K, Kumakura Y, Ishino Y, Kawakami S, Inoue K, Kojima T, Satoh Y, Mutoh H, Kihira K, Sugano K: "Change in apoptosis in the gastric surface epithelium And glands after eradication of Helicobacter pylori"Dig.Liver Dis.. 35. 78-84 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ratineau C, Petry MW, Mutoh H, Leiter AB: "Cyclin D1 represses the basic helix loop helix transcription factor, BETA2/NeuroD."J Biol.Chem.. 277. 8847-8853 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Eda A, Osawa H, Yanaka I, Satoh K, Mutoh H, Kihira K, Sugano K: "Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia."J.Gastroenterol.. 37. 94-100 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Satoh K, Mutoh H, Eda A, Yanaka I, Osawa H, Honda S, Kawata H, Kihira K, Sugano K: "Aberrant. expression of CDX2 in the gastric mucosa with and without intestinal metaplasia : effect of eradication of Helicobacter pylon."Helicobacter. 7. 192-198 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Mutoh H, Hakamata Y, Sato K, Eda A, Yanaka I, Honda S, Osawa H, Kaneko Y, Sugano K: "Conversion of gastric mucosa to intestinal metaplasia in Cdx2-expressing transgenic mice."Biochem.Biophys.Res.Commun. 294. 470-479 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wang J, Tahara K, Hakamata Y, Mutoh H, Murakami T, Takahashi M, Kusama M, Kobayashi E: "Auxiliary partial liver grafting in rats : effect of host hepatectomy on graft regeneration, and review of literature on surgical technique."Microsurgery. 22. 371-377 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Eda A, Osawa H, Satoh K, Yanaka I, Kihira K, Ishino Y, Mutoh H, Sugano K: "Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa."J.Gastroenterol.. 38. 14-22 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Satoh K, Kawata H, Tokumaru K, Kumakura Y, Ishino Y, Kawakami S, Inoue K, Kojima T, Satoh Y, Mutoh H, Kihira K, Sugano K: "Change in apoptosis in the gastric surface epithelium and glands after eradication of Helicobacter pylon."Dig.Liver Dis.. 35. 78-84 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Mutoh H, Sakurai S, Satoh K, Osawa H, Hakamata Y, Takeuchi T, Sugano K: "Cdx1-induced intestinal metaplasia in the transgenic mouse stomach : comparative study with Cdx2 transgenic mice."Gut. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より