PAX6 Alone and Synergistically with PTEN Suppresses the Expression of Vascular Endothelial Growth Factor in Glioblastoma Cells
Glioblastoma multiforme (GBM) is the most malignant primarybrain tumor. High expression of vascular endothelial growthfactor (VEGF) has been a hallmark of GBM. However, the regulationof VEGF expression in malignant gliomas is not well understood.We have previously reported that the transcription factor PAX6suppresses the tumorigenecity of glioblastoma cells. In addition,there is a reverse correlation between the expression levelof PAX6 and VEGF when human glioma tumors and the surroundingnormal tissues were compared, suggesting that PAX6 might regulateVEGF expression. In this study, several techniques such as real-timequantitative reverse transcription PCR, enzyme-linked immunosorbentassay and immunohistochemistry were used to investigate if PAX6regulates VEGF expression in glioma cell lines. Our resultsshowed a significant reduction of VEGF expression in the PAX6stable-transfected glioma cell line U251HF grown both in vitroand in subcutaneous xenografts in nude mice. We further demonstratedin two glioma cell lines (U251HF and U87) that VEGF expressionwas markedly suppressed by adenoviral-mediated overexpressionof PAX6, as well as PTEN. Interestingly, in cells when bothgenes were overexpressed together, VEGF expression was furthersuppressed. Co-immunoprecipitation identified the existenceof physical association between PAX6 and PTEN in the situationwhere the enhanced suppression of VEGF expression occurred.This discovery revealed a novel mechanism underlying the tumor-suppressionfunctions of both PAX6 and PTEN in malignant gliomas. Data fromthis study are consistent with our previous finding in whichpatients with malignant gliomas have significantly more favorableoutcomes when their tumors have high PAX6 and PTEN expressionlevels compared to patients with low expression values for eitheror both genes.
Mayes, D. A.,
Yung, W. K.,
& Zhou, Y.
(2006). PAX6 Alone and Synergistically with PTEN Suppresses the Expression of Vascular Endothelial Growth Factor in Glioblastoma Cells. Cancer Research, 66, 249.