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 different mitogen activated protein (MAP) kinases, dependent on the specific 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-1 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.
Meyer
Ralph G
RG
Section of Radiobiology and Molecular Environmental Research, Department of Radiotherapy, University of Tübingen, Germany.
Küpper
Jan-Heiner
JH
Kandolf
Reinhard
R
Rodemann
H Peter
HP
D000730:Androstadienes / Q000494:pharmacology; D000841:Anisomycin / Q000494:pharmacology; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000528:radiation effects*; D011725:Pyridines / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases
D000730:Androstadienes; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D005419:Flavonoids; D007093:Imidazoles; D017874:Immediate-Early Proteins; D011725:Pyridines; D014157:Transcription Factors; D005576:Colforsin; D013498:Suramin; D004815:Epidermal Growth Factor; D000841:Anisomycin; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin