Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome.

摘要

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.