Int J Cancer 2012 Feb;130 (3): 593-601. [IF:4.926]
Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome.
Guan H , Cai J , Zhang N , Wu J , Yuan J , Li J , Li M .
Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
中山大学附属第一医院内分泌科
Abstract
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.
摘要：
Sp1是第一个得到确认的转录因子，与人类多种形式癌症的发生及进展相关。然而，Sp1在神经胶质瘤中的临床意义及生物学角色仍缺乏了解。在本研究中，我们发现Sp1在神经胶质瘤细胞系及组织中表达显著升高。对222例石蜡包埋神经胶质瘤组织标本的免疫组织化学分析表明的绝大部分组织呈Sp1表达为阳性，并且58.6%呈高水平表达。统计分析表明Sp1的高表达与神经胶质瘤患者WHO疾病分级（p <0.001）及存活状态(p < 0.001)密切相关。多参数分析表明Sp1的表达可能是神经胶质瘤患者存活的独立预后指标。另外，研究发现Sp1在神经胶质瘤细胞上的过表达能增加肿瘤细胞的侵入性。与之相对的是，采用siRNA沉默Sp1基因则能抑制肿瘤细胞的侵袭。我们还发现Sp1上调能增加MMP-2（基质金属蛋白酶-2）的表达及活性。概括来说，我们的结果表明Sp1可能作为神经胶质瘤的一种有效的预后指标，并参与肿瘤侵袭的调节。
