Establishment of a new gastric carcinogenesis model based on epigenetic changes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08373
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Yokohama City University
• Principal Investigator: MAEDA Shin 横浜市立大学, 医学研究科, 教授 (40415956)
• Co-Investigator(Kenkyū-buntansha): 須江 聡一郎 横浜市立大学, 附属病院, 助教 (00738619)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: エピゲノム / 初期化因子 / マウスモデル

Outline of Final Research Achievements

It is becoming clear that changes in gene expression due to epigenome modification may be important in considering gastric carcinogenesis. In this study, we created a mouse considering the development of gastric cancer using a reprogramming mouse for the construction of a gastric cancer mouse model based on epigenome changes. Reprogramming factors (OSKM: Oct3 / 4, Sox2, Klf4, c-Myc) are activated in the stomach using Sox2-cre and Foxa3-cre, which are gastric-specific promoter mice. As a result, no tumor developed due to the expression of reprogramming factors. Although the expression of many reprogramming factors is observed in chronic inflammation, the possibility of direct carcinogenesis was negative from this study. In addition, no tumor development was observed even when a deficiency of the tumor suppressor gene TP53 was added.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

慢性炎症で起こるエピゲノム変化と発癌との関連性を解析するためにマウスモデルの作成を試みたが、作成に至らなかった。発癌遺伝子変異の追加により、胃癌モデル作成を行う必要がある。