Significance of histone modification in pancreatic carcinogenesis affected by tissue inflammation

• Project/Area Number: 18K15804
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Saito Tomotaka 東京大学, 医学部附属病院, 助教 (10815781)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 膵癌 / 膵がん / 膵臓癌

Outline of Final Research Achievements

The entire mechanisms by which epigenetic modifiers contribute to the development of pancreatic cancer remain unknown. The aim was to examine the role of histone methyltransferase Ehmt in pancreatic carcinogenesis by the gene-targeting mouse model. P48Cre:KrasG12D mouse pancreata spontaneously develop acinar ductal metaplasia (ADM) and finally cancer lesions. In the process, ADM cells drive out non-ADM cells by cell-competition. This research addressed the significance of Ehmt in the cell competition- related pancreatic carcinogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究の主眼は、組織炎症下での膵癌発生促進におけるエピジェネテイクス転写制御の意義とそのメカニズムを明らかにすることである。その際の学術的意義として「細胞競合とヒストン修飾の相関」の視点を取り入れた点がある。つまり本研究は膵前癌病変における「細胞競合におけるヒストン修飾の重要性」を新たに示唆する独自性を有する。

Research Products

• [Journal Article] Long-term Risk of Malignancy in Branch-Duct Intraductal Papillary Mucinous Neoplasms. (2020)
  • Author(s): Oyama H, Tada M, Takagi K, Tateishi K, Hamada T, Nakai Y, Hakuta R, Ijichi H, Ishigaki K, Kanai S, Kogure H, Mizuno S, Saito K, Saito T, Sato T, Suzuki T, Takahara N, Morishita Y, Arita J, Hasegawa K, Tanaka M, Fukayama M, Koike K.
  • Journal Title: Gastroenterology. Volume: 158 Issue: 1 Pages: 226-237
  • DOI: 10.1053/j.gastro.2019.08.032
  • Peer Reviewed