Establishment of a novel mouse colon cancer disease model with different genome instability useful for subclass classification

2016 Fiscal Year Final Research Report

• Project/Area Number: 25293284
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Department of Clinical Research, National Hospital Organization Kure Medical Center (2016); Hiroshima University (2013-2015)
• Principal Investigator: Hinoi Takao 独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, 臨床研究部室長 (10444689)
• Co-Investigator(Renkei-kenkyūsha): SOTOMARU Yusuke 広島大学, 自然科学研究支援開発センター, 教授 (90309352) ; IKENOUE Tsuneo 東京大学, 医科学研究所, 准教授 (80396712) ; OUE Naohide 広島大学, 医歯薬保健学研究院, 准教授 (60346484) ; TOMONAGA Takeshi 独立行政法人医薬基盤研究所, プロジェクトリーダー (80227644) ; OHDAN Hideki 広島大学, 医歯薬保健学研究院, 教授 (10363061)
• Research Collaborator: ADACHI Tomohiro ; SAITO Yasufumi ; MIGUCHI Masashi ; NIITSU Hiroaki
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 大腸癌 / マウスモデル / バイオマーカー / RAS / TGFbetaRII

Outline of Final Research Achievements

We applied two types of genomic instability in advanced colon cancer mouse model (colonic epithelial cell specific conditional Apc-knockout mouse) that we established and added another carcinogen driver gene (Kras, TGFβIIR)mutation to Apc mutation to generate complex genetically modified mouse model. The tumor of Apc+Kras mutant mouse was moderately differentiated adenocarcinoma and by comprehensive gene analysis Glut1 and Rcan2 were identified as upregulated and downregluated target genes, respectively. In Apc + TGFβIIRk deficient mice, the expression of GSDMC transcript and protein was elevated. From these mice models, biomarkers useful for treatment such as correlation of genotype-phenotype of oncogenic driver gene and target gene could be identified.

Free Research Field

消化器外科