Hypoxic regulation of the expression of anti-angiogenic genes in U87 glioma cells with loss of function of ern1 signaling enzyme

Abstract

The angiogenesis is an important component of tumor growth and tightly associated with hypoxia. The expression level of genes related to regulation of angiogenesis (BAI2, SPARC, TIMP1, TIMP2, TIMP3, TIMP4, THBS1, THBS2, ADAMTS5 and FGF2) in glioma U87cells and cells with suppressed function of signaling enzyme ERN1, a major mediator of the endoplasmic reticulum stress by qPCR, was studied. We have shown that the expression of genes encoding BAI2, SPARC, TIMP2, TIMP3, THBS1 and THBS2 is strongly increased in glioma cells with ERN1 signaling enzyme loss of function, being more intense for TIMP2, TIMP3 and THBS1 genes. At the same time, the expression of genes encoding TIMP1, TIMP4, ADAMTS5 and FGF2 is significantly decreased with more strong effect for ADAMTS5 and TIMP4 genes. At hypoxia, the expression of most of studied genes in both glioma cell types is affected. Hypoxia induced the expression of TIMP1, TIMP3 and ADAMTS5 genes both in control glioma cells and cells with ERN1 enzyme loss of function. However, the effect of hypoxia towards TIMP2 gene expression was observed only in control glioma cells. At the same time, the expression of genes encoding BAI2, SPARC, THBS1, THBS2, ADAMTS5 and FGF2 is decreased under hypoxia action, but its expression mostly depended on ERN1 signaling enzyme function. The results of this study provide strong evidence that suppression of ERN1 signaling enzyme function, as well as hypoxia, changes the expression of genes related to regulation of angiogenesis in glioma cells. It is possible that changes in the expression of these genes contribute to the suppression of glioma cells’ proliferation by blockade of ERN1 signaling enzyme functioning.

Keywords

• gene expression
• bai2
• sparc
• timp1
• timp2
• timp3
• timp4
• thbs1
• thbs2
• adamts5
• fgf2
• ern1
• glioma cells
• hypoxia