Abstract
Human promyelocytic leukemia HL-60 cells are well known to differentiate into granulocytes or monocytes in the presence of some agents such as DMSO or PMA, respectively. Differentiated HL-60 cells become resistant to some apoptotic stimuli including anticancer drugs or irradiation though undifferentiated cells significantly respond to these stimuli. TRAIL (TNF-related apoptosis-inducing ligand) which is also known as Apo2 ligand (Apo2L), a new member of TNF family, can induce apoptosis in some tumor cells but not in many normal cells. We show here that apoptosis is well induced in HL-60 cells by TRAIL, but susceptibility to TRAIL is reduced during granulocytic differentiation by DMSO. We also suggest some possible mechanisms by which granulocytic differentiated cells become resistant to TRAIL-induced apoptosis. First, in granulocytic differentiated cells, expression of antagonistic decoy receptors for TRAIL (TRAIL-R3/TRID/DcR1/LIT and TRAIL-R4/TRUNDD/DcR2) were enhanced. In addition, expression of Toso, a cell surface apoptosis regulator, seemed to block activation of caspase-8 by TRAIL via enhanced expression of FLIPL in granulocytic differentiated cells. These findings suggest that differentiated cells are resistant using plural mechanisms against various apoptosis-inducing stimuli rather than undifferentiated cells.
MeSH terms
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Apoptosis / immunology*
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Apoptosis Regulatory Proteins
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases / metabolism
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Cell Differentiation / immunology
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GPI-Linked Proteins
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Gene Expression / physiology
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Granulocytes / cytology*
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Granulocytes / enzymology
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HL-60 Cells / cytology*
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HL-60 Cells / enzymology
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Humans
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Intracellular Signaling Peptides and Proteins*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor, Member 10c
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Necrosis Factor Decoy Receptors
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism*
Substances
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Apoptosis Regulatory Proteins
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CASP8 and FADD-Like Apoptosis Regulating Protein
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CFLAR protein, human
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Carrier Proteins
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FCMR protein, human
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GPI-Linked Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Membrane Proteins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 10c
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TNF-Related Apoptosis-Inducing Ligand
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TNFRSF10C protein, human
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TNFSF10 protein, human
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Tumor Necrosis Factor Decoy Receptors
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Tumor Necrosis Factor-alpha
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CASP3 protein, human
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CASP8 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases