bcl-2 protein downregulation is not required for differentiation of multidrug resistant HL60 leukemia cells

Leuk Res. 1996 Feb;20(2):101-7. doi: 10.1016/0145-2126(95)00103-4.


Parental and multidrug resistant HL60 leukemia cell lines were used to study coupling of expression of apoptotic/cytostatic (bcl-2, bax, bclxL, p21/Waf1, and c-myc) genes during differentiation. The multidrug resistant HL60 cell line, HL60/ADR, was less sensitive than parental cells to cytostatic activity of low (0.4-2 ng/ml) doses of PMA. However, during treatment with standard differentiating doses of PMA (10 ng/ml), no difference between the two cell lines in cytostasis and differentiation was found. Downregulation of c-myc and upregulation of p21/Waf1 proteins showed the same time-course in both cell lines. The bcl-2 mRNA was rapidly downregulated while bax and bclxL gene expression was not altered in both differentiating HL60 and HL60/ADR cells. Significant downregulation of bcl-2 protein occurred only in parental HL60 cells. In HL60/ADR, despite rapid cessation of bcl-2 protein synthesis, almost no change in steady-state bcl-2 protein level was found. The lack of bcl-2 protein downregulation was a result of the prolonged half-life of this protein in HL60/ADR cells. Thus, although downregulation of bcl-2 mRNA is coupled to differentiation, actual loss of bcl-2 protein is not required for accomplishment of the differentiation program.

MeSH terms

  • Blotting, Western
  • Cell Differentiation / drug effects
  • Down-Regulation*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Genes, myc
  • HL-60 Cells / drug effects
  • HL-60 Cells / pathology*
  • Half-Life
  • Humans
  • Leukemia, Promyelocytic, Acute / genetics
  • Leukemia, Promyelocytic, Acute / pathology
  • Oncogene Protein p21(ras) / genetics
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc / genetics
  • Tetradecanoylphorbol Acetate / pharmacology
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • bcl-2-Associated X Protein
  • Oncogene Protein p21(ras)
  • Tetradecanoylphorbol Acetate