Expression of insulin-like growth factor binding protein genes and its hypoxic regulation in U87 glioma cells depends on ERN1 mediated signaling pathway of endoplasmic reticulum stress
| Autor: | Oleksandr H. Minchenko, Dmytro O. Minchenko, L L Karbovskyi, Kharkova Ap |
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| Rok vydání: | 2015 |
| Předmět: |
Endocrinology
Diabetes and Metabolism medicine.medical_treatment Protein Serine-Threonine Kinases Insulin-like growth factor-binding protein Endocrinology Cell Line Tumor Gene expression Endoribonucleases medicine Humans IGFBP1 biology Chemistry Brain Neoplasms Endoplasmic reticulum Growth factor Glioma Endoplasmic Reticulum Stress Molecular biology Cell Hypoxia Cell biology ERN1 Gene Expression Regulation Neoplastic Insulin-Like Growth Factor Binding Proteins Gene Knockdown Techniques HTRA1 biology.protein Signal transduction Signal Transduction |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1210-0668 |
| Popis: | OBJECTIVE The aim of the present study was to examine the association between the expression of insulin-like growth binding protein-1 and -2 (IGFBP1 and IGFBP2), insulin-like growth factor 2 mRNA binding protein 3/KH domain containing protein over-expressed in cancer (IGF2BP3/KOC1), and HtrA serine peptidase 1/serine protease with IGF-binding domain (HTRA1/PRSS11) genes and function of endoplasmic reticulum stress signaling mediated by ERN1 (endoplasmic reticulum to nucleus signaling 1) as well as the regulation of these genes by hypoxia in U87glioma cells. METHODS The expression of IGFBP1, IGFBP2, IGF2BP3, and HTRA1 genes in U87 glioma cells and its subline with ERN1 signaling enzyme loss of function, were analyzed by qPCR. Cells underwent to hypoxia exposure (3% oxygen, 16 h). RESULTS The blockade of both enzymatic activities (kinase and endoribonuclease) of ERN1 in glioma cells led to a significant down-regulation of the expression of IGFBP1, IGFBP2, and IGF2BP3 genes and strong up-regulation of HTRA1. At the same time, the inhibition of ERN1 endoribonuclease significantly increased the expression of IGFBP1, IGFBP2, and HTRA1 genes and did not affect the IGF2BP3 gene expression. Hypoxia up-regulated the expression of IGFBP1 and IGFBP2 genes in control glioma cells, with more significant changes in IGFBP1 gene. Furthermore, effect of hypoxia on these gene expressions was significantly lower in glioma cells without ERN1 signaling enzyme function. CONCLUSIONS Results of this study demonstrate the dependence of insulin-like growth binding proteins as well as IGF2BP3 and HTRA1 gene expressions in U87 glioma cells on ERN1 signaling enzyme function and hypoxia, indicating its participation in the regulation of metabolic and proliferative processes via IGF/INS receptors, because endoplasmic reticulum stress is an important component of tumor growth and metabolic diseases. |
| Databáze: | OpenAIRE |
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