Document Detail

bcl-2 protein downregulation is not required for differentiation of multidrug resistant HL60 leukemia cells.
MedLine Citation:
PMID:  8628007     Owner:  NLM     Status:  MEDLINE    
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.
M V Blagosklonny; M Alvarez; A Fojo; L M Neckers
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Leukemia research     Volume:  20     ISSN:  0145-2126     ISO Abbreviation:  Leuk. Res.     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-06-21     Completed Date:  1996-06-21     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  101-7     Citation Subset:  IM    
Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
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MeSH Terms
Blotting, Western
Cell Differentiation / drug effects
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Genes, myc
HL-60 Cells / drug effects,  pathology*
Leukemia, Promyelocytic, Acute / genetics,  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
Reg. No./Substance:
0/BAX protein, human; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Proto-Oncogene Proteins c-myc; 0/bcl-2-Associated X Protein; 16561-29-8/Tetradecanoylphorbol Acetate; EC Protein p21(ras)

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