EGR-1 induction is required for maximal radiosensitivity in A375-C6 melanoma cells

Mansoor M. Ahmed, Kolaparthi Venkatasubbarao, Sana M. Fruitwala, Sumathi Muthukkumar, David P. Wood, Stephen F. Sells, Mohammed Mohiuddin, Vivek M. Rangnekar

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65 Scopus citations

Abstract

Exposure to ionizing radiation leads to induction of the immediate- early gene, early growth response-1 (Egr-1). Previous studies have suggested distinct cell type-and inducer-specific roles for EGR-1 protein in cellular growth inhibition. The present study was undertaken to determine the functional role of EGR-1 in growth inhibition caused by exposure of tumor cells to ionizing radiation. Exposure to ionizing radiation caused induction of EGR-1 protein in human melanoma cells A375-C6. Inhibition of either the function of EGR-1 protein by stable transfection with a dominant-negative mutant or the expression of EGR-1 by transient transfection with an antisense oligomer resulted in a diminished growth-inhibitory response to ionizing radiation. Because previous studies have suggested that mutations in the tumor-suppressor gene p53 confer radio-resistance, we examined the p53 status of A375-C6 cells. Interestingly, both the parental and the transfected A375- C6 cells showed trisomy for wild-type p53 alleles. Exposure to ionizing radiation resulted in induction of p53 protein that localized to the nucleus in A375-C6 cells. These data suggest that inhibition of EGR-1 function confers radio resistance despite the induction of wild-type nuclear p53. Thus, EGR-1 is required for the growth-inhibitory response to ionizing radiation in A375-C6 cells.

Original languageEnglish (US)
Pages (from-to)29231-29237
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number46
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ahmed, M. M., Venkatasubbarao, K., Fruitwala, S. M., Muthukkumar, S., Wood, D. P., Sells, S. F., Mohiuddin, M., & Rangnekar, V. M. (1996). EGR-1 induction is required for maximal radiosensitivity in A375-C6 melanoma cells. Journal of Biological Chemistry, 271(46), 29231-29237. https://doi.org/10.1074/jbc.271.46.29231