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Auf, G., Jabouille, A., Guérit, S., Pineau, R., Delugin, M., Bouchecareilh, M., Favereaux, A., Maitre, M., Gaiser, T., Von Deimling, A., Czabanka, M., Vajkoczy, P., Chevet, E., Bikfalvi, A. and Moenner, M. (2010) A shift from an angiogenic to invasive phenotype induced in malignant glioma by inhibition of the unfolded protein response sensor IRE1. Proceedings of the National Academy of Sciences of the United States of America, 107, 15553- 15558. doi:10.1073/pnas.0914072107

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• TITLE: Expression of casein kinase genes in glioma cell line U87: Effect of hypoxia and glucose or glutamine deprivation

  AUTHORS: Dmytro O. Minchenko, Leonid L. Karbovskyi, Serhii V. Danilovskyi, Anastasia P. Kharkova, Oleksandr H. Minchenko

  KEYWORDS: mRNA Expression; Casein Kinase 1A; 1D; 1G2; 1G3; 1E; 2A1; 2A2; 2B and NUCKS1; Glioma Cells; Endoplasmic Reticulum-Nuclei-1 (ERN1; IRE-1α); Hypoxia; Glucose and Glutamine Deprivation

  JOURNAL NAME: Natural Science, Vol.4 No.1, January 14, 2012

  ABSTRACT: The endoplasmic reticulum-nuclei-1 (ERN1) sensing and signaling enzyme mediates a set of complex intracellular signaling events known as the unfolded protein response. We have studied the effect of hypoxia and ischemic conditions (glucose or glutamine deprivation) on the expression of several casein kinase-1 and -2 genes in glioma U87 cells and its subline with suppressed function of ERN1. It was shown that blockade of ERN1, the key endoplasmic reticulum stress sensor, leads to an increase in the expression levels of casein kinase-1G2, -1E, -2B and NUCKS1 mRNA, but suppresses casein kinase-1A1, -1D and -2A1. Moreover, the expression levels of casein kinase-1A1, -1D and 1G3 as well as casein kinase-2A1 and -2A2 mRNAs are significantly increased under glutamine dep- rivation conditions both in control and ERN1- deficient glioma cells. At the same time, casein kinase-1E, -2B and NUCKS1 mRNA expression levels are also increased under this condition, but only in cells with suppressed function of ERN1. The expression level of NUCKS1 mRNA, however, is decreased both in control glioma cells and in genetically modified cells, but casein kinase-1G2—only in control U87 cells. Cell exposure to glucose deprivation conditions enhances the expression levels of casein kinase- 1D, 1G3, -1E and -2A1 in both types of glioma cells used, but casein kinase-2B expression levels increase only in cells with suppressed function of ERN1. Hypoxia induces or suppresses the expression of most of the studied genes mainly in ERN1-knockdown cells only. Results of this study show that hypoxia as well as glutamine and glucose deprivation conditions change the expression level most of casein kinase genes and that these effects are dependent on ERN1 signaling enzyme function.