Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays
Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays
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DOI：
10.1002/pmic.200500555
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发表时间：
2006-05-01
期刊：
影响因子：
3.4
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Jiang, Rongcai;Mircean, Cristian;Zhang, Wei
利用基因芯片在基因组水平上对胶质瘤的进展进行了广泛的研究。然而，在蛋白质翻译和翻译后水平上的系统检查要有限得多。我们从82种不同的原代胶质瘤组织中构建了胶质瘤蛋白裂解物阵列，并研究了参与细胞增殖、细胞存活、细胞凋亡、血管生成和细胞侵袭等信号通路的46种不同蛋白的表达和磷酸化。一种分析算法被用来稳健地估计这些样本中的蛋白质表达。根据区分37个胶质母细胞瘤(高级别胶质瘤)和45个低级别胶质瘤的能力，下列12种蛋白被鉴定为最强大的鉴别因子：IBα、EGFRpTyr845、AKTpThr308、磷脂酰肌醇3-激酶(PI3K)、BadpSer136、胰岛素样生长因子结合蛋白(IGFBP)2、Igfbp5、基质金属蛋白酶9(MMP9)、血管内皮生长因子(VEGF)、磷酸化视网膜母细胞瘤蛋白(PRB)、Bcl2和c-Abl。聚类分析显示PI3K与AKTpThr308、Igfbp5与IGFBP2、IBα与EGFRpTyr845之间存在剂量关联。另一种抹布包括MMP9、Bc l-2、VEGF和pRb。这些聚集模式可能暗示了功能关系，这值得进一步研究。AKT在Thr308位的磷酸化与胶质母细胞瘤有关，而与Ser473无关，提示PI3K通路激活在胶质瘤进展中是一种特殊的事件。
The progression of gliomas has been extensively studied at the genomic level using cDNA microarrays. However, systematic examinations at the protein translational and post-translational levels are far more limited. We constructed a glioma protein lysate array from 82 different primary glioma tissues, and surveyed the expression and phosphorylation of 46 different proteins involved in signaling pathways of cell proliferation, cell survival, apoptosis, angiogenesis, and cell invasion. An analysis algorithm was employed to robustly estimate the protein expressions in these samples. When ranked by their discriminating power to separate 37 glioblastomas (high-grade gliomas) from 45 lower-grade gliomas, the following 12 proteins were identified as the most powerful discriminators: IB alpha, EGFRpTyr845, AKTpThr308, phosphatidylinositol 3-kinase (PI3K), BadpSer136, insulin-like growth factor binding protein (IGFBP) 2, IGFBP5, matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), phosphorylated retinoblastoma protein (pRB), Bcl-2, and c-Abl. Clustering analysis showed a dose link between PI3K and AKTpThr308, IGFBP5 and IGFBP2, and IB alpha and EGFRpTyr845. Another duster includes MMP9, Bcl-2, VEGF, and pRB. These clustering patterns may suggest functional relationships, which warrant further investigation. The marked association of phosphorylation of AKT at Thr308, but not Ser473, with glioblastoma suggests a specific event of PI3K pathway activation in glioma progression.