Bcl-2 interferes with the execution phase, but not upstream events, in glucocorticoid-induced leukemia apoptosis

Oncogene. 1999 Jan 21;18(3):713-9. doi: 10.1038/sj.onc.1202339.


Due to their growth arrest- and apoptosis-inducing ability, glucocorticoids (GC) are widely used in the therapy of various lymphoid malignancies. Cell death is associated with activation of members of the interleukin-1beta-converting enzyme (ICE) protease/caspase family and, is presumably prevented by the anti-apoptotic protein Bcl-2. To further address the role of Bcl-2 in GC-mediated cytotoxicity, we generated subclones of the GC-sensitive human T-cell acute lymphoblastic leukemia line CCRF-CEM, in which transgenic Bcl-2 expression is regulated by tetracycline. Up to about 48 h, exogenous Bcl-2 almost completely protected these cells from apoptosis, digestion of poly-ADP ribose polymerase (PARP) and generation of Asp-Glu-Val-Asp cleaving (DEVDase) activity. However, when the cells were cultured for another 24 h in the continuous presence of GC, they underwent massive apoptosis that was associated with DEVDase activity and PARP cleavage. Bcl-2 did not markedly affect GC-mediated growth arrest, thereby separating the anti-proliferative from the apoptosis-inducing effect of GC. Moreover, Bcl-2 did not prevent the dramatic reduction in the levels of several mRNAs observed during GC treatment, including the transgenic Bcl-2 mRNA. Thus, Bcl-2 can be placed upstream of effector caspase activation, but downstream of other GC-regulated events, such as growth arrest and the potentially critical repression of steady state levels of multiple mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Division
  • Enzyme Activation
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Glucocorticoids / pharmacology*
  • Growth Inhibitors / pharmacology*
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell
  • Peptide Hydrolases / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger
  • Tumor Cells, Cultured


  • Glucocorticoids
  • Growth Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Poly(ADP-ribose) Polymerases
  • Peptide Hydrolases
  • DEVDase