Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, PR China.
Int J Biochem Cell Biol. 2012 May;44(5):770-5. doi: 10.1016/j.biocel.2012.01.017. Epub 2012 Jan 31.
The identification of heterozygous mutations (with an incidence up to 85%) in either the R132 residue of isocitrate dehydrogenase-1 (IDH1) or the R172 residue of IDH2 in human low-grade diffuse gliomas was remarkable because no oncogenic pathway had been previously documented correlated with these enzymes. In spite of a recent surge in elucidating the tumorigenic activity of IDH mutations in glioblastoma, the underlying biological mechanisms remain poorly understood. We showed here that C6 glioma cells transiently over-expressing IDH2(R172G) induced nuclear accumulation of β-catenin, up-regulation of HIF-1α signaling and corresponding proteins expression that were closely related with tumor invasion and chemo-resistance. These results demonstrated a functional model in which IDH mutations were closely interrelated with glioma progression and could hold some therapeutic implications for future human glioma treatment.
在人类低级别弥漫性神经胶质瘤中，异柠檬酸脱氢酶-1（IDH1）的 R132 残基或 IDH2 的 R172 残基的杂合突变（发生率高达 85%）的鉴定引人注目，因为此前没有与这些酶相关的致癌途径被记录。尽管最近在阐明胶质母细胞瘤中 IDH 突变的致瘤活性方面取得了突飞猛进的进展，但潜在的生物学机制仍知之甚少。我们在这里表明，瞬时过表达 IDH2（R172G）的 C6 神经胶质瘤细胞诱导β-连环蛋白核积累、HIF-1α 信号转导上调以及与肿瘤侵袭和化疗耐药密切相关的相应蛋白表达。这些结果表明了一个功能模型，其中 IDH 突变与胶质瘤的进展密切相关，并可能对未来人类胶质细胞瘤的治疗具有一定的治疗意义。
