| Project/Area Number |
16K10758
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Saga University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
阿部 竜也 佐賀大学, 医学部, 教授 (40281216)
若宮 富浩 佐賀大学, 医学部, 客員研究員 (50773769)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | グリオーマ / TET / 悪性神経膠腫 / 膠芽腫 / エピジェネティクス / 悪性脳腫瘍 / 癌の代謝 / 脳神経 / 癌 / 分子生物学 |
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| Outline of Final Research Achievements |
The mRNA expression of TET1, 2 and 3 were measured in glioblastoma cell lines and glioma stem like cells, which established from surgical specimens of glioma patients. The expression levels of TET1 and 3 showed an inverse correlation. 5-methylcocytocine and 5-hydroxymethylcytosine, which the former is a substrate and the latter is a metabolite of TET were measured by ELISA. The expression of mRNA and enzyme activity were not correlated.
In immunohistochemistory for specimens of gliomas, expression of TET1 protein observed in nuclear or cytoplasm depending on IDH genotype. IDH mutant gliomas expressed TET1 protein in nuclear, while IDH wild gliomas showed cytoplasmic expression of TET1.
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| Academic Significance and Societal Importance of the Research Achievements |
がんの代謝という側面とエピゲノム異常という側面の両者を橋渡す位置に存在するTETに注目し、膠芽腫細胞株および腫瘍幹細胞株のTET1,2,3の遺伝子発現を評価した。TET1蛋白発現は核内と細胞質に分かれIDH1遺伝子変異との間に相関関係があった。IDH変異は2HGを介して、TET蛋白酵素活性を阻害し、5-hydroxymethylcytosine(5hmC)の減少しメチル化を調整している、一方IDH 野生型グリオーマでも5hmCの減少は観察されている。したがって、TET1蛋白の核からの排除が、IDH変異のないgliomaに おける5hmCの減少に関与している可能性があると考えられる。
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