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The vascular endothelial growth factor genes expression in glioma U87 cells is dependent from ERN1 signaling enzyme function

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DOI: 10.4236/abc.2012.22024    4,003 Downloads   8,065 Views   Citations

ABSTRACT

The expression of different vascular endothelial growth factor (VEGF) genes was studied in glioma U87 cells with endoplasmic reticulum–nuclei-1 (ERN1) loss of function and its regulation by hypoxia and glutamine or glucose deprivation conditions as model of ischemia. The blockade of function of the ERN1 enzyme, which is a major sensor of endoplasmic reticulum stress, leads to a decrease of the VEGFA, VEGFB and VEGFC mRNA expression level. The level of VEGFA proteins also decreases at this experimental condition in the cytosolic fraction, but increases in the nuclear fraction. Hypoxia does not affect VEGFC and increases the expression level of VEGFA and VEGFB mRNA in both used cell types, however, the change was much less profound in cells with suppressed function of ERN1. The expression level of VEGFC mRNA decreases in both used cell types in glutamine deprivation condition, however, the change was more profound in control glioma cells. At the same time, the expression level of VEGFA mRNA increases and VEGFB—decreases in gluta-mine deprivation condition in control glioma cells only. Exposure of glioma cells to glucose deprivation condition increases VEGFB mRNA expression level in both used cell types; however, VEGFA—in control glioma cells only and VEGFC—in cells with ERN1 signaling enzyme loss of function only. Thus, the results of this study clearly demonstrated the down-regulation of the expression of all three VEGF genes in glioma cells with ERN1 loss of function which correlates to the suppressed angiogenesis and proliferation rate of these cells. Moreover, the effect of hy-poxia and glutamine or glucose deprivation condition on the expression level of all VEGF genes is different and mainly depends on ERN1 signaling enzyme function.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Minchenko, D. , Kubaichuk, K. , Ratushna, O. , Komisarenko, S. and Minchenko, O. (2012) The vascular endothelial growth factor genes expression in glioma U87 cells is dependent from ERN1 signaling enzyme function. Advances in Biological Chemistry, 2, 198-206. doi: 10.4236/abc.2012.22024.

References

[1] Yalcin, A., Telang, S., Clem, B. and Chesney, J. (2009) Regulation of glucose metabolism by 6-phosphofructo-2- kinase/fructose-2,6-bisphosphatases in cancer. Experimental and Molecular Pathology, 86, 174-179. doi:10.1016/j.yexmp.2009.01.003
[2] Wolf, A., Agnihotri, S., Micallef, J., Mukherjee, J., Sabha, N., Cairns, R., Hawkins, C. and Guha, A. (2011) Hexo-kinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. Journal of Experimental Medicine, 208, 313-326. doi:10.1084/jem.20101470
[3] Rider, M. H., Bertrand, L., Vertommen, D., Michels, P.A., Rousseau, G.G. and Hue, L. (2004) 6-phosphofructo-2- kinase/fructose-2,6-biphosphatase: head-head with a bifunctional enzyme that controls glycolysis. Biochemical Journal, 381, 561-579. doi:10.1042/BJ20040752
[4] Minchenko, A.G., Leshchinsky, I., Opentanova, I.L., Sang, N., Srinivas, V., Armstead, V.E. and Caro, J. (2002) Hypo- xia-inducible factor-1-mediated expression of the 6-pho- sphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFK- FB3) gene. The Journal of Biological Chemistry, 277, 6183-6187. doi:10.1074/jbc.M110978200
[5] Minchenko, O., Opentanova, I. and Caro, J. (2003) Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose- 2,6-bisphosphatase gene family (PFKFB-1-4) expression in vivo. FEBS Letters, 554, 264-270. doi:10.1016/S0014-5793(03)01179-7
[6] Minchenko, O.H., Opentanova, I.L., Minchenko, D.O., Ogura, T. and Esumi, H. (2004) Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-bis-phospha- tase 4 gene via hypoxia-inducible factor-1alpha activation. FEBS Letters, 576, 14-20. doi:10.1016/j.febslet.2004.08.053
[7] Minchenko, O.H., Ochiai, A., Opentanova, I.L., Ogura, T., Minchenko, D.O., Caro, J., Komisarenko, S.V. and Esumi, H. (2005) Overexpression of 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors. Biochimie, 87, 1005-1010. doi:10.1016/j.biochi.2005.04.007
[8] Chesney, J. (2006) 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase and tumor cell glycolysis. Current Opinion in Clinical Nutrition & Metabolic Care, 9, 535-539. doi:10.1097/01.mco.0000241661.15514.fb
[9] Bartrons, R. and Caro, J. (2007) Hypoxia, glucose metabolism and the Warburg’s effect. Journal of Bioenergetics and Biomembranes, 39, 223-229. doi:10.1007/s10863-007-9080-3
[10] Yalcin, A., Clem, B.F., Simmons, A., Lane, A., Nelson, K., Clem, A.L., Brock, E., Siow, D., Wattenberg, B., Telang, S. and Chesney, J. (2009) Nuclear targeting of 6-phos- phofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinase. The Journal of Biological Chemistry, 284, 24223-24232. doi:10.1074/jbc.M109.016816
[11] Denko, N.C. (2008) Hypoxia, HIF1 and glucose metabolism in the solid tumour, Nature Reviews Cancer, 8, 705- 713. doi:10.1038/nrc2468
[12] Minchenko, A., Bauer, T., Salceda, S. and Caro, J. (1994) Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo. Laboratory Investigation, 71, 374-379.
[13] Minchenko, D.O., Bobarykina, A.Y., Senchenko, T.Y., Hubenya, O.V., Tsuchihara, K., Ochiai, A., Moenner, M., Esumi, H. and Minchenko, O.H. (2009) Expression of the VEGF, Glut1 and 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase-3 and -4 in human cancers of the lung, colon and stomach. Studia Biologica, 1, 25-34.
[14] Drogat, B., Auguste, P., Nguyen, D.T., Bouchecareilh, M., Pineau, R., Nalbantoglu, J., Kaufman, R.J., Chevet, E., Bikfalvi, A. and Moenner, M. (2007) IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo. Cancer Research, 67, 6700- 6707. doi:10.1158/0008-5472.CAN-06-3235
[15] Moenner, M., Pluquet, O., Bouchecareilh, M. and Chevet, E. (2007) Integrated endoplasmic reticulum stress respon- ses in cancer. Cancer Research, 67, 10631-10634. doi:10.1158/0008-5472.CAN-07-1705
[16] Hetz, C. and Glimcher, L.H. (2009) Fine-tuning of the unfolded protein response: Assembling the IRE1alpha interactome. Molecular Cell, 35, 551-561. doi:10.1016/j.molcel.2009.08.021
[17] Aragón, T., van Anken, E., Pincus, D., Serafimova, I.M., Korennykh, A.V., Rubio, C.A. and Walter, P. (2009) Messenger RNA targeting to endoplasmic reticulum stress signalling sites. Nature, 457, 736-740. doi:10.1038/nature07641
[18] Saito, A., Ochiai, K., Kondo, S., Tsumagari, K., Murakami, T., Cavener, D.R. and Imaizumi, K. (2011) Endopla-smic reticulum stress response mediated by the PERK- eIF2-ATF4 pathway is involved in osteoblast differentiation induced by BMP2. The Journal of Biological Chemistry, 286, 4809-4818. doi:10.1074/jbc.M110.152900
[19] Bi, M., Naczki, C., Koritzinsky, M., Fels, D., Blais, J., Hu, N., Harding, H., Novoa, I., Varia, M., Raleigh, J., Scheuner, D., Kaufman, R.J., Bell, J., Ron, D., Wouters, B.G. and Koumenis, C. (2005) ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO Journal, 24, 3470-3481. doi:10.1038/sj.emboj.7600777
[20] Blais, J.D., Filipenko, V., Bi, M., Harding, H.P., Ron, D., Koumenis, C., Wouters, B.G. and Bell, J.C. (2004) Transcription factor 4 is translationally regulated by hypoxic stress, Molecular and Cellular Biology, 24, 7469-7482. doi:10.1128/MCB.24.17.7469-7482.2004
[21] Fels, D.R. and Koumenis, C. (2006) The PERK/eIF2- a/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer Biology and Therapy, 5, 723-728. doi:10.4161/cbt.5.7.2967
[22] Luo, D., He, Y., Zhang, H., Yu, L., Chen, H., Xu, Z., Tang, S., Urano, F. and Min, W. (2010) AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response. The Journal of Biological Chemistry, 283, 11905- 11912. doi:10.1074/jbc.M710557200
[23] Korennykh, A.V., Egea, P.F., Korostelev, A.A., Finer- Moore, J., Zhang, C., Shokat, K.M., Stroud, R.M. and Walter, P. (2009) The unfolded protein response signals through high-order assembly of Ire1. Nature, 457, 687- 693. doi:10.1038/nature07661
[24] Romero-Ramirez, L., Cao, H., Nelson, D., Hammond, E., Lee, A.H., Yoshida, H., Mori, K., Glimcher, L.H., Denko, N.C., Giaccia, A.J., Le, Q.T. and Koong, A.C. (2004) XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Cancer Research, 64, 5943-5947. doi:10.1158/0008-5472.CAN-04-1606
[25] Lin, J.H., Li, H., Yasumura, D., Cohen, H.R., Zhang, C., Pannin, B., Shokat, K.M., Lavail, M.M. and Walter, P. (2007). IRE1 signaling affects cell fate during the un- folded protein response, Science, 318, 944-949. doi:10.1126/science.1146361
[26] J. Hollien, J.H. Lin, H. Li, N. Stevens, P. and Walter, J.S. (2009) Weissman, regulated Ire1-dependent decay of messenger RNAs in mammalian cells, Journal of Cell Bio- logy, 186, 323-331. doi:10.1083/jcb.200903014
[27] Acosta-Alvear, D., Zhou, Y., Blais, A., Tsikitis, M., Lents, N.H., Arias, C., Lennon, C.J., Kluger, Y. and Dynlacht, D.D. (2007) XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Molecular Cell, 27, 53-66. doi:10.1016/j.molcel.2007.06.011
[28] Han, D., Upton, J.-P., Hagen, A., Callahan, J., Oakes, S.A. and Papa, F.R. (2008) A kinase inhibitor activates the IRE1alpha RNase to confer cytoprotection against ER stress. Biochemical and Biophysical Research Communications, 365, 777-783. doi:10.1016/j.bbrc.2007.11.040
[29] 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. The Proceeding of the National Academy of Sciences of the United States of America, 107, 1555-15558.
[30] Ferrara, N., Gerber, H.P. and LeCouter, J. (2003) The biology of VEGF and its receptors, Nature Medicine, 9, 669-676. doi:10.1038/nm0603-669
[31] Weiss, T.W., Simak, R., Kaun, C., Rega, G., Pfluger, H., Maurer, G., Huber, K. and Wojta, J. (2011) Oncostatin M and IL-6 induce u-PA and VEGF in prostate cancer cells and correlate in vivo. Anticancer Research, 31, 3273-3278.
[32] Kumar, B., Chile, S.A., Ray, K.B., Reddy, G.E., Addepalli, M.K., Kumar, A.S., Ramana, V. and Rajagopal, V. (2011) VEGF-C differentially regulates VEGF-A expression in ocular and cancer cells; promotes angiogenesis via RhoA mediated pathway. Angiogenesis, 14, 371-380. doi:10.1007/s10456-011-9221-5
[33] Byrne, A.M., Bouchier-Hayes, D.J. and Harmey J.H. (2005) Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). Journal of Cellular and Molecular Medicine, 9, 777-794. doi:10.1111/j.1582-4934.2005.tb00379.x
[34] Minchenko, D.O., Karbovskyi, L.L., Danilovskyi, S.V., Moenner, M. and Minchenko, O.H. (2012) Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line. American Journal of Molecular Biology, 2, 142-152. doi:10.4236/ajmb.2012.21003
[35] Armstead, V.E., Minchenko, A.G., Campbell, B. and Lefer, A.M. (1997) P-selectin is up-regulated in vital organs during murine traumatic shock. FASEB Journal, 11, 1271- 1279.
[36] Drogat, B., Bouchecareilh, M., North, S., Petibois, C., Deleris, G., Chevet, E., Bikfalvi, A. and Moenner, M. (2007) Acute L-glutamine deprivation compromises VEGF-A up-regulation in A549/8 human carcinoma cells. Journal of Cellular Physiology, 212, 463-472. doi:10.1002/jcp.21044

  
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