Differential gene expression profiling in human brain tumors
Differential gene expression profiling in human brain tumors
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DOI：
10.1152/physiolgenomics.2001.5.1.21
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发表时间：
2001-02-07
影响因子：
4.6
通讯作者：
Benos, DJ
中科院分区：
文献类型：
--
作者：
Markert, JM;Fuller, CM;Benos, DJ
使用寡核苷酸微阵列对三个人类颞叶脑组织样本（正常）和四个原发性多形性胶质母细胞瘤（GBM）肿瘤进行基因表达谱分析。此外，通过全细胞膜片钳、免疫组织化学染色和RT-PCR来确认表达改变。我们的结果鉴定了一些离子和溶质转运相关基因，例如N-甲基-D-天冬氨酸（NMDA）受体、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）-2受体、GABA（A）受体亚基α3、β1、β2和β3、谷氨酸转运蛋白、谷氨酸/天冬氨酸转运蛋白II、钾通道K(V)2.1、与正常组织相比，hK(V)beta3 和钠/质子交换器 1 (NHE-1) 在肿瘤中均下调。相比之下，水通道蛋白-1，可能是水通道蛋白-3和-5，以及GLUT-3信息在肿瘤中似乎上调。我们的结果还证实了之前的研究结果，即骨桥蛋白、烟酰胺 N-甲基转移酶、鼠双微体 2 (MDM2) 和上皮蛋白（颗粒蛋白）在 GBM 中表达上调。我们还首次证明细胞因子和 p53 结合蛋白、巨噬细胞迁移抑制因子 (MIF) 在 GBM 中似乎上调。这些结果表明，离子和溶质转运基因以及迄今为止未被怀疑的细胞因子（即 MIF）的调节可能对脑肿瘤细胞生物学产生深远的影响，因此可能确定 GBM 中潜在的有用治疗靶点。
Gene expression profiling of three human temporal lobe brain tissue samples (normal) and four primary glioblastoma multiforme (GBM) tumors using oligonucleotide microarrays was done. Moreover, confirmation of altered expression was performed by whole cell patch clamp, immunohistochemical staining, and RT-PCR. Our results identified several ion and solute transport-related genes, such as N-methyl-D-aspartate (NMDA) receptors, alpha -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 receptors, GABA(A) receptor subunits alpha3, beta1, beta2, and beta3, the glutamate transporter, the glutamate/aspartate transporter II, the potassium channel K(V)2.1, hK(V)beta3, and the sodium/proton exchanger 1 (NHE-1), that are all downregulated in the tumors compared with the normal tissues. In contrast, aquaporin-1, possibly aquaporins-3 and -5, and GLUT-3 message appeared upregulated in the tumors. Our results also confirmed previous work showing that osteopontin, nicotinamide N-methyltransferase, murine double minute 2 (MDM2), and epithelin (granulin) are upregulated in GBMs. We also demonstrate for the first time that the cytokine and p53 binding protein, macrophage migration inhibitory factor (MIF), appears upregulated in GBMs. These results indicate that the modulation of ion and solute transport genes and heretofore unsuspected cytokines (i.e., MIF) may have profound implications for brain tumor cell biology and thus may identify potential useful therapeutic targets in GBMs.