Glucocorticoid mediated transcriptional repression of c-myc in apoptotic human leukemic CEM cells

J Steroid Biochem Mol Biol. 2000 Jul-Aug;73(5):195-202. doi: 10.1016/s0960-0760(00)00080-7.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / physiology*
  • Dactinomycin / pharmacology
  • Dexamethasone / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, Reporter
  • Genes, myc*
  • Glucocorticoids / pharmacology*
  • Humans
  • Kinetics
  • Luciferases / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Promoter Regions, Genetic / drug effects*
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / genetics
  • Transcription, Genetic / drug effects*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Glucocorticoids
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Dactinomycin
  • Dexamethasone
  • Luciferases