This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sells, S. F. Articles by Rangnekar, V. M. Search for Related Content PubMed PubMed Citation Articles by Sells, S. F. Articles by Rangnekar, V. M.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 02 1995, 682-692, Vol 15, No. 2
Copyright © 1995, American Society for Microbiology

The zinc finger transcription factor EGR-1 impedes interleukin-1- inducible tumor growth arrest

SF Sells, S Muthukumar, VP Sukhatme, SA Crist and VM Rangnekar
Department of Surgery, University of Kentucky, Lexington 40536.

Interleukin-1 (IL-1) is a growth arrest signal for diverse human tumor cell lines. We report here that the action of this cytokine in melanoma cells is associated with induction of EGR-1, a zinc finger protein that activates gene transcription. Both growth arrest and EGR-1 are induced via the type I receptor of IL-1. To determine the role of EGR-1 in IL-1 action in melanoma cells, we used a chimera expressing the transrepression domain of the Wilm's tumor gene, WT1, and the DNA binding domain of Egr-1. This chimera competitively inhibited EGR-1- dependent transactivation via the GC-rich DNA binding sequence, indicating that it acted as a functional dominant negative mutant of Egr-1. Melanoma cell lines stably transfected with the dominant negative mutant construct were supersensitive to IL-1 and showed accelerated G0/G1 growth arrest compared with the parental cell line. The effect of the dominant negative mutant construct was mimicked by addition of an antisense Egr-1 oligomer to the culture medium of the parental cells: the oligomer inhibited EGR-1 expression and accelerated the growth-inhibitory response to IL-1. These data imply that EGR-1 acts to delay IL-1-mediated tumor growth arrest.

This article has been cited by other articles:

• Shareef, M. M., Brown, B., Shajahan, S., Sathishkumar, S., Arnold, S. M., Mohiuddin, M., Ahmed, M. M., Spring, P. M. (2008). Lack of P-Glycoprotein Expression by Low-Dose Fractionated Radiation Results from Loss of Nuclear Factor-{kappa}B and NF-Y Activation in Oral Carcinoma Cells. Mol Cancer Res 6: 89-98 [Abstract] [Full Text]  
• Chen, Y., Alm, K., Vujcic, S., Kramer, D. L., Kee, K., Diegelman, P., Porter, C. W. (2003). The Role of Mitogen-activated Protein Kinase Activation in Determining Cellular Outcomes in Polyamine Analogue-treated Human Melanoma Cells. Cancer Res. 63: 3619-3625 [Abstract] [Full Text]  
• Carleton, M., Haks, M. C., Smeele, S. A. A., Jones, A., Belkowski, S. M., Berger, M. A., Linsley, P., Kruisbeek, A. M., Wiest, D. L. (2002). Early Growth Response Transcription Factors Are Required for Development of CD4-CD8- Thymocytes to the CD4+CD8+ Stage. J. Immunol. 168: 1649-1658 [Abstract] [Full Text]  
• Nishi, H., Nishi, K. H., Johnson, A. C. (2002). Early Growth Response-1 Gene Mediates Up-Regulation of Epidermal Growth Factor Receptor Expression during Hypoxia. Cancer Res. 62: 827-834 [Abstract] [Full Text]  
• Fitzgerald, K. A., O'Neill, L. A. J. (1999). Characterization of CD44 Induction by IL-1: A Critical Role for Egr-1. J. Immunol. 162: 4920-4927 [Abstract] [Full Text]  
• Nalca, A., Rangnekar, V. M. (1998). The G1-phase Growth-arresting Action of Interleukin-1 Is Independent of p53 and p21/WAF1 Function. J. Biol. Chem. 273: 30517-30523 [Abstract] [Full Text]  
• Muthukkumar, S., Han, S.-S., Muthukkumar, S., Rangnekar, V. M., Bondada, S. (1997). Role of Egr-1 Gene Expression in B Cell Receptor-induced Apoptosis in an Immature B Cell Lymphoma. J. Biol. Chem. 272: 27987-27993 [Abstract] [Full Text]  
• Nair, P., Muthukkumar, S., Sells, S. F., Han, S.-S., Sukhatme, V. P., Rangnekar, V. M. (1997). Early Growth Response-1-dependent Apoptosis Is Mediated by p53. J. Biol. Chem. 272: 20131-20138 [Abstract] [Full Text]  
• Yang, D., Hayashi, H., Takii, T., Mizutani, Y., Inukai, Y., Onozaki, K. (1997). Interleukin-1-induced Growth Inhibition of Human Melanoma Cells. INTERLEUKIN-1-INDUCED ANTIZYME EXPRESSION IS RESPONSIBLE FOR ORNITHINE DECARBOXYLASE ACTIVITY DOWN-REGULATION. J. Biol. Chem. 272: 3376-3383 [Abstract] [Full Text]  
• Ahmed, M. M., Venkatasubbarao, K., Fruitwala, S. M., Muthukkumar, S., Wood, D. P. Jr., Sells, S. F., Mohiuddin, M., Rangnekar, V. M. (1996). EGR-1 Induction Is Required for Maximal Radiosensitivity in A375-C6 Melanoma Cells. J. Biol. Chem. 271: 29231-29237 [Abstract] [Full Text]  
• Hofer, G., Grimmer, C., Sukhatme, V. P., Sterzel, R. B., Rupprecht, H. D. (1996). Transcription Factor Egr-1 Regulates Glomerular Mesangial Cell Proliferation. J. Biol. Chem. 271: 28306-28310 [Abstract] [Full Text]  
• Muthukkumar, S., Sells, S. F., Crist, S. A., Rangnekar, V. M. (1996). Interleukin-1 Induces Growth Arrest by Hypophosphorylation of the Retinoblastoma Susceptibility Gene Product RB. J. Biol. Chem. 271: 5733-5740 [Abstract] [Full Text]  
• Komine, M., Rao, L. S., Kaneko, T., Tomic-Canic, M., Tamaki, K., Freedberg, I. M., Blumenberg, M. (2000). Inflammatory Versus Proliferative Processes in Epidermis. TUMOR NECROSIS FACTOR alpha INDUCES K6b KERATIN SYNTHESIS THROUGH A TRANSCRIPTIONAL COMPLEX CONTAINING NFkappa B AND C/EBPbeta. J. Biol. Chem. 275: 32077-32088 [Abstract] [Full Text]  
• Murai, T., Nakagawa, Y., Maeda, H., Terada, K. (2001). Altered Regulation of Cell Cycle Machinery Involved in Interleukin-1-induced G1 and G2 Phase Growth Arrest of A375S2 Human Melanoma Cells. J. Biol. Chem. 276: 6797-6806 [Abstract] [Full Text]