Glucocorticoid mediated transcriptional repression of c-myc in apoptotic human leukemic CEM cells.
Suppression of c-myc has been implicated as a critical event in some glucocorticoid-evoked apoptotic systems. It is therefore of interest to understand the mechanism of glucocorticoid-regulation of the c-myc gene. In the present study, a detailed analysis of dexamethasone (Dex)-evoked regulation of the human c-myc gene in human leukemic CEM-C7 cells has been performed. Dex suppresses c-myc mRNA and immunoreactive protein expression in clone CEM-C7 and subclone CEM-C7-14 cells. Nuclear run-on assays suggested that the regulation occurred at the level of transcription initiation. The half-life of c-myc mRNA was approximately 30 min and its stability was not affected by Dex treatment. In addition, Dex suppressed luciferase gene expression driven by -2052 to +34 bp c-myc promoter in transfected CEM-C7-14 cells. This result further supports that c-myc gene is suppressed by Dex at the transcriptional level in apoptotic human leukemic cells.
Zhou
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F
Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, TX 77555-0645, USA.
Medh
R D
RD
Thompson
E B
EB
D017209:Apoptosis / Q000502:physiology*; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter; D016259:Genes, myc; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003609:Dactinomycin; D003907:Dexamethasone; D008156:Luciferases