Up-Regulation of Vascular Endothelial Growth Factor Expression in a Rat Glioma Is Conferred by Two Distinct Hypoxia-driven Mechanisms

作者: Georg Breier , Marcia Machein , Annette Damert , Masaki Q. Fujita , Masaki Q. Fujita

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摘要: Up-regulation of vascular endothelial growth factor (VEGF) expression is a major event leading to neovascularization in malignant gliomas. Hypoxia believed be the crucial environmental stimulus for this up-regulation. To critically assess hypothesis, we asked whether mechanisms defined previously hypoxia-induced VEGF vitro are similarly involved and sufficient up-regulation gene vivo , using lacZ reporter under control regulatory sequences an experimental glioma model. Inclusion binding site hypoxia-inducible 1 (HIF 1) 5′ used hybrid produced weak β-galactosidase staining special tumor cell subtype, so-called perinecrotic palisading (PNP) cells that flank necrotic regions within tumor. Deletion HIF abolished PNP cells, indicating transcriptional activation gliomas mediated by 1. 3′ untranslated from contructs resulted increased suggesting mRNA stabilization also contributes glioblastoma growing as solid tumors. Combination flanking region including along with levels cells. EF 5 immunostaining low oxygen partial pressure covered same were stained β-galactosidase. Collectively, data provide evidence activated distinct subpopulation, gliomas, two hypoxia-driven mechanisms.

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