Evolutionary machanism of pancreatic ductal adenocarcinoma mediated by (pro)renin receptor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07690
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kagawa University
• Principal Investigator: Shibayama Yuki 香川大学, 医学部, 研究員 (90401190)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: (プロ)レニン受容体 / 膵管癌 / ゲノム不安定性 / ドライバー遺伝子

Outline of Final Research Achievements

The purpose of this study is to clarify the evolutionary pattern of pancreatic ductal adenocarcinoma (PDAC) using prorenin receptor [(P)RR]-expressing human pancreatic ductal epithelial cells. The nuclear morphology of (P)RR-expressing human pancreatic ductal epithelial cells in passage 6 showed multinucleation, which is considered to occur as the malignancy of the cancer increases, and chromosomal aberrations were also identified. This result was supported by whole human genome analysis, which showed no mutations in driver genes of PDAC, such as KRAS and p16 in(P)RR- expressing human pancreatic ductal epithelial cells at passage 6. On the other hand, mutations in the KRAS and p16 genes were observed in (P)RR-expressing human pancreatic ductal epithelial cells at passage 20, suggesting that the presence of chromosomal aberrations may contribute to malignant transformation of PDAC.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

学術的意義：大規模な染色体構造変異および体細胞突然変異を包含する(P)RR安定発現ヒト膵管上皮細胞を用いて、ヒト膵管癌の進化パターンを前向きに検討した結果、膵管癌を代表するドライバー遺伝子KRASおよびp16の体細胞突然変異を生じるだけではなく、膵管癌の悪性化のスピードを促進する”断続的進化”の存在を示唆した。社会的意義：(P)RRは膵管癌を直接的に形成する因子であることが判明したことから、創薬において極めて重要な分子ターゲットになることが考えられた。