Експресія генів IGF1R, IGFBP4 та IGFBP5 у клітинах гліоми лінії U87 за умов дефіциту глутаміну

Abstract

We have studied the expression of insulin-like growth factor receptor (IGF1R) and insulin-like growth factor binding protein (IGFBP4 and IGFBP5) genes in U87 glioma cells upon glutamine deprivation condition in relation to inhibition of ERN1 (endoplasmic reticulum to nuclei signaling 1), a sensor and signaling enzyme of endoplasmic reticulum stress, which control cell proliferation. It was shown that exposure control glioma cells upon glutamine deprivation condition leads to up-regulation of IGFBP4 and down-regulation of IGF1R expression at the mRNA level in control glioma cells, but IGFBP5 gene expression in these cells does not depend upon glutamine deprivation. At the same time, inhibition of IRE1 modifies the effect of glutamine deprivation on the expression of IGFBP5 gene because in glioma cells without functional activity of ERN1 glutamine deprivation leads to suppression of this IGFBP. We have also shown that the expression of all studied genes in glioma cells is regulated by ERN1 signaling enzyme at standard condition because ERN1 inhibition significantly enhances the expression of IGFBP4 and IGFBP5 genes. Proteins encoded by these genes are major inhibitors of pro-proliferative activity of insulin-like growth factors IGF1 and IGF2. We have also shown upregulation of the expression level of IGF1R gene in glioma cells with ERN1 knockdown as compared to control glioma cells. Results of this study shown that glutamine deprivation affects the expression of studied genes and that ERN1 inhibition preferentially changes these genes expression.