Functional activation of EphA5 receptor does not promote cell proliferation in the aberrant EphA5 expressing human glioblastoma U-118 MG cell line
Functional activation of EphA5 receptor does not promote cell proliferation in the aberrant EphA5 expressing human glioblastoma U-118 MG cell line
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DOI：
10.1016/s0006-8993(99)01112-9
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发表时间：
1999-03-06
期刊：
影响因子：
2.9
通讯作者：
Miescher, GC
中科院分区：
文献类型：
--
作者：
Bruce, V;Olivieri, G;Miescher, GC
Eph受体是受体酪氨酸激酶（RTK）的一个亚家族，其被肝配蛋白配体激活，并且似乎在神经系统发育期间的轴突引导和细胞迁移中起重要作用。Eph受体的过度表达或组成性激活与各种肿瘤中的增殖增加有关。我们最近描述了EphA 5在原发性人星形细胞瘤、胶质母细胞瘤和人胶质母细胞瘤U-118 MG细胞系中的谱系异常表达。EphA 5表达在这些肿瘤中的作用并不明显，我们已经使用人胶质母细胞瘤U-118 MG细胞系作为模型研究了EphA 5活化的细胞效应。免疫荧光染色显示EphA 5的细胞表面表达。使用肝配蛋白-A1重组融合蛋白激活EphA 5受体以时间依赖性方式导致EphA 5的酪氨酸磷酸化。暴露于肝配蛋白-A1的U-118 MG胶质母细胞瘤细胞未导致显著的自发或FCS刺激的细胞增殖，尽管观察到轻微减少。这与Eph激活在其他肿瘤细胞系中的作用匡威，并且是第一项研究胶质母细胞瘤细胞系中EphA 5的研究。(C)1999 Elsevier Science B. V.保留所有权利。
Eph receptors are a subfamily of receptor tyrosine kinases (RTKs), that are activated by ephrin ligands and appear to play important roles in axon guidance and cell migration during development of the nervous system. Over-expression or constitutive activation of Eph receptors has been linked with increased proliferation in various tumours. We have recently described lineage aberrant expression of EphA5 in primary human astrocytomas, glioblastomas and in the human glioblastoma U-118 MG cell Line. A role for EphA5 expression in these tumours is not apparent, and we have investigated the cellular effects of EphA5 activation using the human glioblastoma U-118 MG cell line as a model. Immunofluorescent staining demonstrated cell surface expression of EphA5. Activation of the EphA5 receptor using an ephrin-A1 recombinant fusion protein resulted in tyrosine phosphorylation of EphA5 in a time-dependent manner. Exposure of U-118 MG glioblastoma cells to ephrin-A1 did not result in significant spontaneous or FCS-stimulated cell proliferation, though a marginal decrease was observed. This is in converse to the effects of Eph activation in other tumour cell Lines, and is the first study to investigate EphA5 in glioblastoma cell lines. (C) 1999 Elsevier Science B.V. All rights reserved.