Eps8 promotes cellular growth of human malignant gliomas
Eps8 promotes cellular growth of human malignant gliomas
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Eps8 促进人类恶性神经胶质瘤的细胞生长。
DOI：
10.3892/or.2012.2160
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发表时间：
2013-02-01
期刊：
影响因子：
4.2
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Ding, Xiaofeng;Zhou, Fangliang;Zhang, Jian
Eps8最初被确定为表皮生长因子受体的底物。Eps8过表达导致有丝分裂信号传导增加和恶性转化。然而，关于Eps8在人类胶质瘤中的重要性，我们知之甚少。在本研究中，我们通过免疫组织化学分析发现，与邻近正常脑组织相比，Eps8在56.6%的人类胶质瘤（WHO分级III级和IV级）中过表达。通过G418筛选，建立了稳定表达Eps8的U251人胶质瘤细胞系，通过细胞存活率、MTT和液体集落形成试验，Eps8的异位表达促进了U251胶质瘤细胞的生长和存活。相比之下，在SHG-44细胞中慢病毒表达Eps8 siRNA导致细胞生长和增殖显著降低。此外，Eps8可调节胶质瘤细胞系和组织中磷酸化细胞外信号调节蛋白激酶（ERK）、磷酸化丝氨酸-苏氨酸蛋白激酶Akt和β -catenin的表达水平。这些结果表明Eps8在胶质瘤中过表达，并可能通过调节ERK和Akt/ β -catenin信号通路影响胶质瘤细胞的生长。因此，Eps8可能是人类胶质瘤治疗的一个新的潜在靶点。
Eps8 was initially identified as a substrate of the epidermal growth factor receptor. Overexpression of Eps8 leads to increased mitogenic signaling and malignant transformation. However, little is known concerning the importance of Eps8 in human gliomas In this study, we found that Eps8 was overexpressed in 56.6% of human gliomas (WHO grades III and IV) compared with adjacent normal brain tissues by immunohistochemical analysis. The U251 human glioma cell line stably expressing Eps8 was established by G418 screening, and the ectopic expression of Eps8 enhanced U251 glioma cell growth and survival by cell survival, MTT and liquid colony formation assays. By contrast, the lentiviral expression of Eps8 siRNA in SHG-44 cells resulted in a significant reduction in cellular growth and proliferation. Furthermore, Eps8 modulated the levels of phosphorylated extracellular signal-regulated protein kinase (ERK), phosphorylated serine-threonine protein kinase Akt and beta-catenin expression in glioma cell lines and tissues. These results suggest that Eps8 is overexpressed in human gliomas, and affects glioma cell growth possibly by regulating ERK and Akt/beta-catenin signaling. Therefore, Eps8 may represent a novel potential target in human glioma therapy.