Comprehensive analyses about factors involved in the progression from IPMN to Pancreatic cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16154
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Saito Kei 東京大学, 医学部附属病院, 届出研究員 (20815617)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膵がん

Outline of Final Research Achievements

IPMN, a cystic disease of the pancreas, is a precancerous pathology of pancreatic cancer. We investigated to identify essential genes in the process from IPMN-like pathology with GNAS mutation to invasive cancer.
As a result, the GNAS mutation caused the GNAS protein to bind to Ran, a chaperone protein that connects the cell nucleus and cytoplasm, resulting in changes in intracellular signaling other than the MAPK pathway, resulting in an increase in chemokine expression and the cell undergoing apoptosis. It was assumed that the cells would fall and increase cell turnover.
Since the increase in cell turnover directly leads to the accumulation of gene mutations, this was considered to be one of the mechanisms of pancreatic carcinogenesis from IPMN.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

年率1-2%と言われるGNAS変異を持つIPMN様病態から浸潤癌に至る人がなぜ存在するのか、GNAS変異から浸潤癌に至るまでの過程における必須の遺伝子を同定することは重要である。今回IPMNからの膵発癌機構のひとつを同定したが、今後これらの機構を追求することで、IPMNからの膵発癌を抑制する手法を開発することに繋がることが期待される。