Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak.

Abstract

We demonstrate that treatment of HCW-2 cells, an apoptotic resistant variant of the human HL-60 promyelocytic leukemia cell line with phorbol-12-myristate acetate (PMA), induced differentiation along the monocytic lineage. During this process there was a dramatic increase in the mitochondrial levels of the apoptosis effector, Bak, due to the stabilization of bak mRNA, which was correlated with the sensitization of HCW-2 cells to respond to the apoptotic effect of staurosporine (STS). Treatment of PMA-differentiated, but not undifferentiated, HCW-2 cells induced processing of Bid, substantial efflux of cytochrome c from mitochondria to the cytosol, activation of caspase-3 and apoptosis. The biological significance of the increased mitochondrial Bak in differentiated HCW-2 cells was supported by the finding that transient transfection of a bak cDNA into HCW-2 cells conferred sensitivity to STS-triggered apoptosis, as determined by pro-caspase-3 processing, cytochrome c efflux and DNA fragmentation. Our results suggest that the induction of Bak, upon monocytic differentiation, may be a critical event that regulates the apoptotic sensitivity of differentiated HCW-2 cells. Oncogene (2000) 19, 4108 - 4116

• Authors: D Chatterjee, P Pantazis, G Li, T A Bremner, E A Hendrickson, J H Wyche
• Journal: Oncogene (Oncogene) Vol. 19 Issue 36 Pg. 4108-16 (Aug 24 2000) ISSN: 0950-9232 [Print] England
• PMID: 10962571 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• BAK1 protein, human
• BH3 Interacting Domain Death Agonist Protein
• BID protein, human
• Carcinogens
• Carrier Proteins
• Cytochrome c Group
• Enzyme Precursors
• Membrane Proteins
• bcl-2 Homologous Antagonist-Killer Protein
• Glyceraldehyde-3-Phosphate Dehydrogenases
• Receptor, Macrophage Colony-Stimulating Factor
• CASP3 protein, human
• Caspase 3
• Caspases
• Tetradecanoylphorbol Acetate

Topics

• Apoptosis
• BH3 Interacting Domain Death Agonist Protein
• Blotting, Northern
• Blotting, Western
• Carcinogens (pharmacology)
• Carrier Proteins (metabolism)
• Caspase 3
• Caspases (metabolism)
• Cell Differentiation
• Cytochrome c Group (metabolism)
• Enzyme Precursors (metabolism)
• Gene Expression Regulation, Leukemic
• Glyceraldehyde-3-Phosphate Dehydrogenases (metabolism)
• Granulocytes (cytology, drug effects, metabolism)
• HL-60 Cells
• Humans
• Membrane Proteins (genetics, metabolism)
• Mitochondria (metabolism)
• Monocytes (cytology, drug effects, metabolism)
• Receptor, Macrophage Colony-Stimulating Factor (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Cells, Cultured
• bcl-2 Homologous Antagonist-Killer Protein