Analysis of pathogenic mechanisms of IPMN using GNAS gene modified mousepathogenic mechanisms

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hyogo Medical University
• Principal Investigator: OHMURAYA Masaki 兵庫医科大学, 医学部, 教授 (60398229)
• Co-Investigator(Kenkyū-buntansha): 古川 徹 東北大学, 医学系研究科, 教授 (30282122)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: IPMN / RNF43

Outline of Final Research Achievements

In this research project, RNF43 gene knockout mice were generated and analyzed. RNF43 encodes an E3 ubiquitin ligase and negatively regulates Wnt signaling. RNF43 KO mice were born according to Mendelian frequency, and there was no difference in their growth as compared to wild. As RNF43 somatic mutations of RNF43 are found in 18% or more of colon cancer and endometrial cancer (Nat Genet, 2014), azoxymethane (AOM) and DSS were administered to mice (AOM / DSS mice) As a result of examining whether there is a difference in cancer carcinogenesis, it was found that the tumor was large and that RNF43 had the function of suppressing the progression of colorectal cancer.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

IPMNではKRAS、GNAS、RNF43遺伝子の変異が重複して見られる。今回はRNF43に関して、そのノックアウトマウスを作製し、単独欠損では膵臓に異常を来さないこと、また大腸発がんモデルを用いると、やはりRNF43が腫瘍発生に抑制的に働いていることが明らかとなった。今後はIPMNに関してもその分子メカニズムを解明することで、新たな治療法の開発につながると予想される。