The role of nuclear receptor CAR in the pathogenesis of intrahepatic cholangiocellular carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Gunma University
• Principal Investigator: Kakizaki Satoru 群馬大学, 大学院医学系研究科, 講師 (80344935)
• Co-Investigator(Kenkyū-buntansha): 山崎 勇一 群馬大学, 医学部附属病院, 助教 (00582404) ; 堀口 昇男 群馬大学, 大学院医学系研究科, 助教 (10550022) ; 井上 裕介 群馬大学, 大学院理工学府, 准教授 (90304302)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 核内受容体 / CAR / 胆管癌 / 化学発癌

Outline of Final Research Achievements

The aim of this study was to investigate the role of nuclear receptor CAR (constitutive androstane receptor) in the pathogenesis of intrahepatic cholangiocarcinoma. Thioacetamide (TAA) was administered to CAR knockout and wild-type mice to create a chemical carcinogenic model of cholangiocarcinoma. Cholangiocarcinoma developed after 24-weeks TAA administration. However, there were no significant differences between the two groups. In the chemical carcinogenesis model of hepatocellular carcinoma, it has been reported that carcinogenesis is significantly suppressed in CAR knockout mice. However, it is not suppressed in the TAA-induced cholangiocarcinoma model used in this study.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌（肝細胞由来）の化学発癌モデルでは、核内レセプターCARの発癌への関与が報告されている。同様に肝臓に発生し、胆管細胞由来の肝内胆管癌においてCARの関与の有無を検討した。Thioacetamide (TAA) による胆管癌モデルで検討したが、CARの関与は明らかでなかった。胆管癌モデルにおいてCARの関与の有無を検討したことは、胆管癌及びCARの病態生理を考える上で意義があったと考える。