Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome
Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome
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Sp1 在人胶质瘤中上调，促进 MMP-2 介导的细胞侵袭并预测不良的临床结果
DOI：
10.1002/ijc.26049
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发表时间：
2012-02-01
影响因子：
6.4
通讯作者：
Li, Mengfeng
中科院分区：
文献类型：
--
作者：
Guan, Hongyu;Cai, Junchao;Li, Mengfeng
Sp1是第一个被鉴定的转录因子，据报道与多种人类癌症类型的发生和进展相关。然而，Sp1在胶质瘤中的临床意义和生物学作用尚不清楚。在这项研究中，我们发现Sp1在胶质瘤细胞系和组织中的表达显着升高。免疫组化分析显示，绝大多数的222石蜡包埋的档案胶质瘤标本检测显示Sp1阳性表达，58.6%的Sp1高水平表达。统计分析表明，Sp1高表达与胶质瘤患者的WHO分级（p < 0.001）和生存状态（p < 0.001）密切相关。Sp1表达较低的患者总生存率高于Sp1表达较高的患者。多因素分析提示Sp1表达可能是胶质瘤患者生存的独立预后指标。此外，发现神经胶质瘤细胞中Sp1的过表达会增加其侵袭力，相反，通过SiRNA沉默Sp1会抑制细胞侵袭力。此外，我们证明，上调Sp1可以增加MMP-2的活性和表达。总的来说，我们的数据表明，Sp1可能是一个有价值的预后标志物胶质瘤，并参与调制肿瘤的侵袭。
Sp1, the first identified transcription factor, has been reported to be associated with the development and progression of various human cancer types. However, the clinical significance and biological role of Sp1 in glioma are less well understood. In this study, we found that the expression of Sp1 was markedly elevated in glioma cell lines and tissues. Immunohistochemistry analysis revealed that the vast majority of 222 paraffin-embedded archival glioma specimens tested displayed positive Sp1 expression, and 58.6% exhibited high-level Sp1 expression. Statistical analysis suggested that the high Sp1 expression was correlated strongly with the WHO grading (p < 0.001) and survival status (p < 0.001) of glioma patients. Patients with lower Sp1 expression had better overall survival than those with higher Sp1 expression. Multivariate analysis suggested that Sp1 expression might be an independent prognostic indicator of the survival of patients with glioma. Furthermore, overexpression of Sp1 in glioma cells was found to increase their invasiveness, and in contrast, silencing Sp1 by siRNA caused an inhibition of cell invasion. Moreover, we demonstrated that the up-regulation of Sp1 could increase activity and expression of MMP-2. Collectively, our data suggest that Sp1 might represent a valuable prognostic marker for glioma and is involved in modulation of tumor invasion.