DOI QR코드

DOI QR Code

Valproic Acid Induces Transcriptional Activation of Human GD3 Synthase (hST8Sia I) in SK-N-BE(2)-C Human Neuroblastoma Cells

  • Kwon, Haw-Young (Department of Biotechnology, Dong-A University) ;
  • Dae, Hyun-Mi (Department of Biotechnology, Dong-A University) ;
  • Song, Na-Ri (Department of Biotechnology, Dong-A University) ;
  • Kim, Kyoung-Sook (Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University) ;
  • Kim, Cheorl-Ho (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University) ;
  • Lee, Young-Choon (Department of Biotechnology, Dong-A University)
  • Received : 2008.06.13
  • Accepted : 2008.10.13
  • Published : 2009.01.31

Abstract

In this study, we have shown the transcriptional regulation of the human GD3 synthase (hST8Sia I) induced by valproic acid (VPA) in human neuroblastoma SK-N-BE(2)-C cells. To elucidate the mechanism underlying the regulation of hST8Sia I gene expression in VPA-stimulated SK-N-BE(2)-C cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5'-flanking region of the hST8Sia I gene by the transient expression method showed that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-${\kappa}B$, functions as the VPA-inducible promoter of hST8Sia I in SK-N-BE(2)-C cells. Site-directed mutagenesis and electrophoretic mobility shift assay indicated that the NF-${\kappa}B$ binding site at -731 to -722 was crucial for the VPA-induced expression of hST8Sia I in SK-N-BE(2)-C cells. In addition, the transcriptional activity of hST8Sia I induced by VPA in SK-N-BE(2)-C cells was strongly inhibited by SP600125, which is a c-Jun N-terminal kinase (JNK) inhibitor, and $G{\ddot{O}}6976$, which is a protein kinase C (PKC) inhibitor, as determined by RT-PCR (reverse transcription-polymerase chain reaction) and luciferase assays. These results suggest that VPA markedly modulated transcriptional regulation of hST8Sia I gene expression through PKC/JNK signal pathways in SK-N-BE(2)-C cells.

Keywords

Acknowledgement

Supported by : Dong-A University

References

  1. Beecken, W.D., Engl, T., Ogbomo, H., Relja, B., Cinatl, J., Bereiter- Hahn, J., Oppermann, E., Jonas, D., and Blaheta, R.A. (2005). Valproic acid modulates NCAM polysialylation and polysialyltransferase mRNA expression in human tumor cells. Int. Immunopharmacol. 5, 757-769 https://doi.org/10.1016/j.intimp.2004.12.009
  2. Blaheta, R.A., Michaelis, M., Driever, P.H., and Cinatl, J. Jr. (2005). Evolving anticancer drug valproic acid: insights into the mechanism and clinical studies. Med. Res. Rev. 25, 383-397 https://doi.org/10.1002/med.20027
  3. Chen, G., Yuan, P.X., Jiang, Y.M., Huang, L.D., and Manji, H.K. (1999). Valproate robustly enhances AP-1 mediated gene expression. Mol. Brain Res. 64, 52-58 https://doi.org/10.1016/S0169-328X(98)00303-9
  4. Chen, F., Castranova, V., and Shi, X. (2001). New insights into the role of nuclear factor-κB in cell growth regulation. Am. J. Pathol. 159, 387-397 https://doi.org/10.1016/S0002-9440(10)61708-7
  5. Cheung, N.K., Saarinen, U.M., Neely, J.E., Landmeier, B., Donovan, D., and Coccia, P.F. (1985). Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. Cancer Res. 45, 2642-2649
  6. Cinatl, J.Jr., Cinatl, J., Scholz, M., Driever, P.H., Henrich, D., Kabickova, H., Vogel, J.U., Doerr, H.W., and Kornhuber, B. (1996). Antitumor activity of sodium valproate in cultures of human neuroblastoma cells. Anticancer Drugs 7, 766-773 https://doi.org/10.1097/00001813-199609000-00008
  7. Cinatl, J.Jr., Cinatl, J., Driever, P.H., Kotchetkov, R., Pouckova, P., Kornhuber, B., and Schwabe, D. (1997). Sodium valproate inhibits in vivo growth of human neuroblastoma cells. Anticancer Drugs 8, 958-963 https://doi.org/10.1097/00001813-199711000-00007
  8. Cinatl, J.Jr., Kotchetkov, R., Blaheta, R., Driever, P.H., Vogel, J.U., and Cinatl, J. (2002). Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: enhancement by combination with interferon-alpha. Int. J. Oncol. 20, 97-106
  9. Ghosh, S., and Karin, M. (2002). Missing pieces in the NF-$\kappa$B puzzle. Cell 109, S81-S96 https://doi.org/10.1016/S0092-8674(02)00703-1
  10. Gottlicher, M., Minucci, S., Zhu, P., Kramer, O.H., Schimpf, A., Giavara, S., Sleeman, J.P., Lo Coco, F., Nervi, C., Pelicci, P.G., et al. (2001). Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 20, 6969-6978 https://doi.org/10.1093/emboj/20.24.6969
  11. Gratsa, A., Rooprai, H.K., Rogers, J.P., Martin, K.K., and Pilkington, G.J. (1997). Correlation of expression of NCAM and GD3 ganglioside to motile behavior in neoplastic glia. Anticancer Res. 17, 4111-4118
  12. Gurvich, N., Tsygankova, O.M., Meinkoth, J.L., and Klein, P.S. (2004). Histone deacetylase is a target of valproic acid-mediated cellular differentiation. Cancer Res. 64, 1079-1086 https://doi.org/10.1158/0008-5472.CAN-03-0799
  13. Hakomori, S. (1981). Glycosphingolipids in cellular interaction, differentiation, and oncogenesis. Annu. Rev. Biochem. 50, 733-764 https://doi.org/10.1146/annurev.bi.50.070181.003505
  14. Hakomori, S., and Igarashi, Y. (1993). Gangliosides and glycosphingolipids as modulators of cell growth, adhesion, and transmembrane signaling. Adv. Lipid Res. 25, 147-162
  15. Johannessen, C.U. (2000). Mechanisms of action of valproate: a commentatory. Neurochem. Int. 37, 103-110 https://doi.org/10.1016/S0197-0186(00)00013-9
  16. Kang, N.Y., Kang, S.K., Lee, Y.C., Choi, H.J., Lee, Y.S., Cho, S.Y., Kim, Y.S., Ko, J.H., and Kim, C.H. (2006). Transcriptional regulation of the human GD3 synthase gene expression in Fasinduced Jurkat T cells: a critical role of transcription factor NF-$\kappa$B in regulated expression. Glycobiology 16, 375-389 https://doi.org/10.1093/glycob/cwj087
  17. Kang, N.Y., Kim, C.H., Kim, K.S., Ko, J.H., Lee, J.H., Jeong, Y.K., and Lee, Y.C. (2007). Expression of the human CMP-NeuAc: GM3 alpha2,8-sialyltransferase (GD3 synthase) gene through the NF-kappaB activation in human melanoma SK-MEL-2 cells. Biochim. Biophys. Acta 1769, 622-630 https://doi.org/10.1016/j.bbaexp.2007.08.001
  18. Phiel, C.J., Zhang, F., Huang, E.Y., Guenther, M.G., Lazar, M.A., and Klein, P.S. (2001). Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J. Biol. Chem. 276, 36734-36741 https://doi.org/10.1074/jbc.M101287200
  19. Rogawski, M.A., and Loscher, W. (2004). The neurobiology of antiepileptic drugs. Nat. Rev. Neurosci. 5, 553-564 https://doi.org/10.1038/nrn1430
  20. Stockhausen, M.T., Sjölund, J., Manetopoulos, C., and Axelson, H. (2005). Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells. Br. J. Cancer 92, 751-759 https://doi.org/10.1038/sj.bjc.6602309
  21. Svennerholm, L. (1980). Gangliosides and synaptic transmission. Adv. Exp. Med. Biol. 125, 533-544
  22. Varki, A. (1993). Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3, 97-130 https://doi.org/10.1093/glycob/3.2.97
  23. Yuan, P.X., Huang, L.D., Jiang, Y.M., Gutkind, J.S., Manji, H.K., and Chen, G. (2001). The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J. Biol. Chem. 276, 31674-31683 https://doi.org/10.1074/jbc.M104309200

Cited by

  1. Transcriptional Regulation of Human GD3 Synthase (hST8Sia I) by Fenretinide in Human Neuroblastoma SH-SY-5Y Cells vol.20, pp.9, 2010, https://doi.org/10.5352/jls.2010.20.9.1332
  2. Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells vol.42, pp.12, 2010, https://doi.org/10.3858/emm.2010.42.12.088
  3. Transcriptional activation of human GM3 synthase (hST3Gal V) gene by valproic acid in ARPE-19 human retinal pigment epithelial cells vol.44, pp.6, 2009, https://doi.org/10.5483/bmbrep.2011.44.6.405
  4. Estradiol Represses the G D3 Synthase Gene ST8SIA1 Expression in Human Breast Cancer Cells by Preventing NFκB Binding to ST8SIA1 Promoter vol.8, pp.4, 2013, https://doi.org/10.1371/journal.pone.0062559
  5. Cordycepin-mediated transcriptional regulation of human GD3 synthase (hST8Sia I) in human neuroblastoma SK-N-BE(2)-C cells vol.46, pp.1, 2009, https://doi.org/10.1093/abbs/gmt122
  6. Upregulation of Human ST8Sia VI (α2,8-Sialyltransferase) Gene Expression by Physcion in SK-N-BE(2)-C Human Neuroblastoma Cells vol.17, pp.8, 2016, https://doi.org/10.3390/ijms17081246
  7. Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer vol.5, pp.4, 2009, https://doi.org/10.3390/cells5040043
  8. Disialyl GD2 ganglioside suppresses ICAM-1-mediated invasiveness in human breast cancer MDA-MB231 cells vol.13, pp.3, 2009, https://doi.org/10.7150/ijbs.16903
  9. Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers vol.8, pp.None, 2018, https://doi.org/10.3389/fonc.2018.00513
  10. Transcriptional Activation of Human GD3 Synthase (hST8Sia I) Gene in Curcumin-Induced Autophagy in A549 Human Lung Carcinoma Cells vol.19, pp.7, 2009, https://doi.org/10.3390/ijms19071943