Glial cell-line derived neurotrophic factor (GDNF) family of ligands confer chemoresistance in a ligand-specific fashion in malignant gliomas
Glial cell-line derived neurotrophic factor (GDNF) family of ligands confer chemoresistance in a ligand-specific fashion in malignant gliomas
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DOI：
10.1016/j.jocn.2008.06.002
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发表时间：
2009-03-01
影响因子：
2
通讯作者：
Too, Heng Phon
中科院分区：
文献类型：
--
作者：
Ng, Wai Hoe;Wan, Guo Qiang;Too, Heng Phon
胶质细胞源性神经营养因子（GDNF）是一种神经营养因子，已知可促进胚胎中脑中多巴胺能神经元的神经元存活，并有助于许多癌症的致癌作用。它在中枢神经系统中普遍存在，表明它在高级星形细胞瘤的有丝分裂发生中发挥作用。 GDNF 在胶质母细胞瘤细胞系和人胶质瘤中过度表达。 GFR α 1b 是人神经胶质瘤中主要的剪接受体亚型，RET9 是主要的共受体。与 GFR α 1a 剪接变体相比，GFR α 1b 剪接同工型存在显着差异性过表达。用GDNF而不是替代配体神经营养因子预处理胶质母细胞瘤细胞系，促进有丝分裂行为并赋予对1,3-双(2-氯乙基)-1-亚硝基脲(BCNU)的化学抗性。 BCNU 和 GDNF 的信号图谱表明，GDNF 促进 Akt 活性和抑制 JNK 活性的能力可能有助于 BCNU 化疗后细胞存活率的增加。 (C) 2008 Elsevier Ltd. 保留所有权利。
Glial cell-line derived neurotrophic factor (GDNF) is a neurotrophic factor known to promote neuronal survival of dopaminergic neurons in the embryonic midbrain as well as contribute to carcinogenesis in many cancers. Its ubiquitous presence in the central nervous system suggests a role in the mitogenesis of high-grade astrocytoma. GDNF is overexpressed in glioblastoma cell lines and human gliomas. GFR alpha 1b is the predominant spliced receptor isoform in human gliomas and RET9 is the predominant co-receptor. Significantly there is differential overexpression of the GFR alpha 1b spliced isoform compared to the GFR alpha 1a spliced variant. Pre-treatment of glioblastoma cell lines with GDNF but not the alternative ligand neurturin, promoted mitogenic behaviour and conferred chemoresistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Signaling mapping of BCNU and GDNF suggest that the ability of GDNF to promote Akt activity and inhibit JNK activity may contribute to the increased cellular survival after BCNU chemotherapy. (C) 2008 Elsevier Ltd. All rights reserved.