2022 Fiscal Year Final Research Report
Molecular Basis of Intrahepatic Cholangiocarcinoma Caused by Epigenomic Abnormalities
| Project/Area Number |
20K08353
|
|---|
| 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 | The University of Tokyo |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
立石 敬介 東京大学, 医学部附属病院, 届出研究員 (20396948)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | 胆管癌 |
|---|
| Outline of Final Research Achievements |
Using a mouse model of intrahepatic cholangiocarcinogenesis, we examined the effects of epigenome-related gene aberrations on malignancy or tumor stroma formation, and the possibility that inhibition of chromatin regulation may also have inhibitory effects on abundant stroma in ICCs. We generated genetically engineered mice capable of inducing tissue-specific expression of wild-type IDH1 or mutant IDH1 (R132C); CAG-LSL-IDH1WT Tg and CAG-LSLIDH1(R132C mutant) Tg. We have confirmed expression of the transgenic IDH1 gene in the liver and production of 2-HG specific to the mutant mice by crossing them with Alb-Cre mice. These were crossed with other transgenic mice and analyzed.
|
| Free Research Field |
消化器病学
|
| Academic Significance and Societal Importance of the Research Achievements |
ICCで変異が認められるエピゲノム関連遺伝子が、その悪性度や豊富な腫瘍間質形成に及ぼす影響については全く不明であり、同時にクロマチン修飾制御との関連も解明されていない。最近ではそれら遺伝子異常がICCにおいても癌細胞のみならず腫瘍間質に作用している可能性が考えられ、同時にクロマチン修飾との関連も推察されるが、その分子機序を解明した報告はない。さらに遺伝子異常の標的化が間質細胞や免疫反応を介した抗腫瘍戦略として有効である可能性も想起される。本研究はエピゲノム異常がもたらす肝内胆管癌の高悪性度形質の分子基盤を明らかにする学術的意義を有する。
|
