Effect of hypoxia on the expression of genes encoding insulin-like growth factors and some related proteins in U87 glioma cells without IRE1 function
| Autor: | Kharkova Ap, L L Karbovskyi, Oleksandr H. Minchenko, Oleh V. Halkin, Dmytro O. Minchenko |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism Protein Serine-Threonine Kinases Diseases of the endocrine glands. Clinical endocrinology Receptor IGF Type 1 stc2 03 medical and health sciences Endocrinology Somatomedins Cell Line Tumor Glioma Endoribonucleases medicine Humans Gene Glycoproteins Insulin-like growth factor 1 receptor ire1 inhibition Regulation of gene expression hypoxia u87 glioma cells Kinase igf1r Transfection RC648-665 medicine.disease Molecular biology Cell Hypoxia Cell biology Gene Expression Regulation Neoplastic igf1 030104 developmental biology Insulin-Like Growth Factor Binding Protein 4 Cell culture igfbp4 Intercellular Signaling Peptides and Proteins mrna expression Signal transduction Signal Transduction |
| Zdroj: | Endocrine Regulations, Vol 50, Iss 2, Pp 43-54 (2016) |
| ISSN: | 1336-0329 |
| DOI: | 10.1515/enr-2016-0008 |
| Popis: | Objective. The aim of the present study was to investigate the effect of hypoxia on the expression of genes encoding insulin-like growth factors (IGF1 and IGF2), their receptor (IGF1R), binding protein-4 (IGFBP4), and stanniocalcin 2 (STC2) in U87 glioma cells in relation to inhibition of endoplasmic reticulum stress signaling mediated by IRE1 (inositol requiring enzyme 1) for evaluation of their possible significance in the control of tumor growth. Methods. The expression of IGF1, IGF2, IGF1R, IGFBP4, and STC2 genes in U87 glioma cells transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia was studied by qPCR. Results. The expression of IGF1 and IGF2 genes is down-regulated in glioma cells without IRE1 signaling enzyme function in comparison with the control cells. At the same time, the expression of IGF1R, IGFBP4, and STC2 genes was up-regulated in glioma cells upon inhibition of IRE1, with more significant changes for IGFBP4 and STC2 genes. We also showed that hypoxia does not change significantly the expression of IGF1, IGF2, and IGF1R genes but up-regulated IGFBP4 and STC2 genes expression in control glioma cells. Moreover, the inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in glioma cells does not change significantly the effect of hypoxia on the expression of IGF1, IGF1R, and IGFBP4 genes but introduces sensitivity of IGF2 gene to hypoxic condition. Thus, the expression of IGF2 gene is resistant to hypoxia only in control glioma cells and significantly down-regulated in cells without functional activity of IRE1 signaling enzyme, which is central mediator of the unfolded protein response and an important component of the tumor growth as well as metabolic diseases. Conclusions. Results of this study demonstrate that the expression of IGF1 and IGF1R genes is resistant to hypoxic condition both in control U87 glioma cells and cells without IRE1 signaling enzyme function. However, hypoxia significantly up-regulates the expression of IGFBP4 gene independently on the inhibition of IRE1 enzyme. These data show that proteins encoded by these genes are resistant to hypoxia except IGFBP4 and participate in the regulation of metabolic and proliferative processes through IRE1 signaling. |
| Databáze: | OpenAIRE |
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