Abstract
Neuroblastomas are characterized by defects in tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induced apoptosis, especially down-regulation and methylation of Caspase-8 (CASP8). This defect is associated with amplification of N-myc. However, N-myc has also been implicated in induction of apoptosis, especially activation of CASP9 mediated apoptosis. Here we found that ectopic N-myc expression induces TRAIL susceptibility, both by CASP8 and CASP9 mediated apoptosis. N-myc did not modify CASP8 expression and methylation. CASP8 defects therefore represent an independent event in neuroblastoma, counteracting the N-myc induced susceptibility to apoptosis. Analysis of the CASP9 mediated route in a series of neuroblastoma cell lines, we found normal expression and no aberrant methylation of four apoptotic intermediates, including CASP9 itself.
MeSH terms
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Apoptosis / drug effects*
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Apoptosis Regulatory Proteins
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Caspase 8
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Caspase 9
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Caspases / genetics
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Caspases / metabolism
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DNA Methylation
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DNA Primers / chemistry
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Enzyme Inhibitors / pharmacology
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Gene Amplification
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Genes, myc / physiology
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Humans
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Membrane Glycoproteins / pharmacology
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Neuroblastoma / metabolism*
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Neuroblastoma / pathology*
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Proto-Oncogene Proteins c-myc / metabolism*
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RNA, Messenger / metabolism
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Receptors, Tumor Necrosis Factor / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology
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Up-Regulation
Substances
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Apoptosis Regulatory Proteins
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DNA Primers
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Enzyme Inhibitors
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Membrane Glycoproteins
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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Receptors, Tumor Necrosis Factor
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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CASP8 protein, human
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CASP9 protein, human
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Caspase 8
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Caspase 9
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Caspases