TAILIEUCHUNG - Báo cáo Y học: Early growth response-1 gene (Egr-1 ) promoter induction by ionizing radiation in U87 malignant glioma cells in vitro

The promoter of the early growth response gene (Egr-1) has been described to be activated by ionizing radiation, and it seems to be clear that this process involves di erent mitogen activated protein (MAP) kinases, dependent on the speci®c cell type examined. However, early steps leading to activation of the corresponding pathways and thus to overexpression of Egr-1 are not well understood. | Eur. J. Biochem. 269 337-346 2002 FEBS 2002 Early growth response-1 gene Egr-1 promoter induction by ionizing radiation in U87 malignant glioma cells in vitro Ralph G. Meyer1 2 Jan-Heiner Kiipper2 Reinhard Kandolf2 and H. Peter Rodemann1 ISection of Radiobiology and Molecular Environmental Research Department of Radiotherapy and 2Department of Molecular Pathology University of Tubingen Germany The promoter of the early growth response gene Egr-I has been described to be activated by ionizing radiation and it seems to be clear that this process involves different mitogen activated protein MAP kinases dependent on the specihc cell type examined. However early steps leading to activation of the corresponding pathways and thus to overexpression of Egr-1 are not well understood. In this study deletion mutants of the 5 upstream region of the Egr-I gene were generated which allowed us to correlate the radiation-induction of the Egr-1 promoter in U87 glioma cells to five serum response elements. Based on the data shown a possible role of two cAMP responsive elements for radiation-dependent promoter regulation could be ruled out. On the basis of activator inhibitor studies applying fetal bovine serum EGF PD98059 anisomycin SB203580 forskolin and wortmannin it could be demonstrated that in U87 cells the ERK1 2 and potentially SAPK JNK but not the p38MAPK SAPK2 pathway contribute to the radiation-induction of Egr-1 promoter. In addition it was observed that irradiated cells secrete a diffusible factor into the culture media which accounts for the radiation-induced promoter upregulation. By blocking growth factor receptor activation with suramin this effect could be completely abolished. Keywords Egr-1 promoter growth factor receptor glioblastoma cells ionizing radiation. The immediate early gene Egr-I synonyms are NGFI-A zif268 TIS8 and krox24 encodes a transcription factor involved in cell growth and differentiation. The DNA binding domain of this protein with its three .

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