EFFECT OF NUTRIENT DEPRIVATION ON THE EXPRESSION OF PDGFC, PDGFRA, AND PDGFRB GENES IN U87 GLIOMA CELLS DEPENDS ON ERN1 SIGNALING ENZYME FUNCTION

Growth factors, which control angiogenesis, play an important role in malignant tumor progression. We studied the effect of glucose or glutamine deprivation conditions on the expression level of platelet derived growth factor C (PDGFC) and its receptors PDGFRA (platelet derived growth factor receptor A) and PDGFRB mRNA in U87 glioma cells. It was shown that the suppression of both enzymatic activities of sensor and signaling enzyme ERN1 (endoplasmic reticulum to nucleus signaling 1), the major component of endoplasmic reticulum stress signaling, upregulates the expression level of genes encoding PDGFC, PDGFRA, and PDGFRB in U87 glioma cells. Glutamine deprivation condition leads to increase the expression level of PDGFC gene and to decrease – PDGFRA and PDGFRB genes in control glioma cells, but ERN1 knockdown modifies the effect of glutamine deprivation on the expression of these genes. It was also shown that the expression level of PDGFC gene did not change significantly in control glioma cells at glucose deprivation condition, but in cells with ERN1 knockdown glucose deprivation decreases the expression of this gene. Results of this investigation clearly demonstrated that the expression of PDGFC, PDGFRA, and PDGFRB genes in U87 glioma cells is dependent from blockade of ERN1-mediated endoplasmic reticulum stress and is mostly regulated by glutamine and glucose deprivation in dependence of ERN1 signaling enzyme function.