Results of this study demonstrated the dependence of INSR and related to insulin receptor signaling gene expressions in U87 glioma cells on ERN1 enzyme function indicating its participation in the regulation of metabolic and proliferative processes via endoplasmic reticulum stress which is important component of tumor growth and metabolic diseases. Moreover, hypoxia and glucose or glutamine deprivation are controlled by the expression of insulin receptor and related to insulin signaling genes mostly via ERN1 enzyme signaling.

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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.

Insulin-like growth factor binding proteins (IGFBPs ) contain insulin-like growth factor (IGF) binding domain and play an important role in the regulation of numerous metabolic and proliferative processes mainly through interaction with IGF1 and IGF2, their cell surface receptors as well as insulin receptor, alter the half-life of the IGFs, modifying their biological activity. It is well known that insulin-like growth factors and the signal transduction networks play important roles in tumorigenesis and metastasis as well as in metabolic diseases [1,2]. IGFBPs participate in endoplasmic reticulum stress, which is an important factor of tumor growth, insulin resistance, and obesity [3][4][5]. It is interesting to note that there is the cross talk between IGF and insulin receptor signaling pathways at the receptor level or at downstream signaling level. This cross talk significantly changed a variety of cancers as a result of insulin receptor isoform. A formation of hybrid receptor isoforms between receptors for IGF1 and insulin, which are sensitive to the stimulation of all three IGF axis ligands, as well as hybrid receptors of IGF1/insulin receptor with other tyrosine kinase potentiate the transformation of cells, tumorigenesis, and tumor neovascularization [6].The IGFBPs have different affinity for insulin-like growth factors. They bind and regulate the availability of both insulin-like growth factors and inhibit or stimulate the growth promoting effects of the IGFs through IGF/INS receptors and through other signaling pathways and regulate cell proliferation and survival as well as angiogenesis and cancer експериментальні роботи doi: http://dx