TAILIEUCHUNG - Báo cáo khoa học: Transgenic Cdx2 induces endogenous Cdx1 in intestinal metaplasia of Cdx2-transgenic mouse stomach

Cdx1 and Cdx2, which are transcription factors regulating normal intesti-nal development, have been studied as potential key molecules in the pathogenesis of the precancerous intestinal metaplasia of the human stomach. However, the regulation of Cdx1 expression in the intestinal metaplasia is poorly understood. | ỊFEBS Journal Transgenic Cdx2 induces endogenous Cdx1 in intestinal metaplasia of Cdx2-transgenic mouse stomach Hiroyuki Mutoh Hiroko Hayakawa Hirotsugu Sakamoto Miho Sashikawa and Kentaro Sugano Department of Medicine Division of Gastroenterology Jichi MedicalUniversity Tochigi Japan Keywords chromatin immunoprecipitation luciferase reporter assay methylation RT-PCR siRNA Correspondence H. Mutoh Department of Medicine Division of Gastroenterology Jichi Medical University Yakushiji 3311-1 Shimotsuke Tochigi 329-0498 Japan Fax 81 285 44 8297 Tel 81 285 58 7348 E-mail muto@ Received 12 April2009 revised 1 August 2009 accepted 6 August 2009 doi Cdxl and Cdx2 which are transcription factors regulating normal intestinal development have been studied as potential key molecules in the pathogenesis of the precancerous intestinal metaplasia of the human stomach. However the regulation of Cdxl expression in the intestinal metaplasia is poorly understood. Cdx2-expressing gastric mucosa of Cdx2-transgenic mouse stomach was replaced by intestinal metaplastic mucosa. The aim of this study was to investigate the following a Cdxl expression in the intestinal metaplastic mucosa of the Cdx2-transgenic mouse stomach and b the relationship between Cdxl and Cdx2. A mouse model of intestinal metaplasia the Cdx2-transgenic mouse was used to investigate Cdx1 gene expression by RT-PCR. DNA methylation profile analysis was performed by bisulfite sequencing and the interaction of Cdx2 with the Cdx1 promoter was examined by chromatin immunoprecipitation assay electrophoretic mobility shift assay and luciferase reporter assays. Cdx2 mRNA was expressed in the Cdx2-transgenic mouse stomach. However endogenous Cdx2 mRNA was not expressed in the intestinal metaplasia of the Cdx2-transgenic mouse stomach. On the other hand endogenous Cdx1 mRNA and protein were expressed in the intestinal metaplasia of the Cdx2-transgenic mouse stomach. The Cdx1 promoter .

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