Abstract
Neuroblastoma is a solid tumor of the sympathetic nervous system accounting for up to 10% of pediatric cancers and 15% of cancer-related deaths. It is a useful system for investigation of stress signal-mediated apoptosis as a tumor suppression mechanism. In this study, we present evidence that p53 mediates DNA damaging drug-induced apoptosis in IMR32 cells through the caspase-9 pathway. In summary, we define a molecular pathway for mediating DNA damaging drug-induced apoptosis in human neuroblastoma IMR32 cells and suggest that inactivation of essential components of this apoptotic pathway may confer drug resistance on neuroblastoma cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibiotics, Antineoplastic / toxicity
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Apoptosis / drug effects*
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Apoptosis / physiology
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Caspase 9 / physiology*
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Cell Line, Tumor / drug effects
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DNA Damage / physiology
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DNA, Neoplasm / drug effects
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Doxorubicin / toxicity
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Genes, p53
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Humans
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Neuroblastoma / pathology*
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RNA Interference
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RNA, Small Interfering / pharmacology
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / physiology*
Substances
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Antibiotics, Antineoplastic
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DNA, Neoplasm
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Neoplasm Proteins
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RNA, Small Interfering
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TP53 protein, human
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Tumor Suppressor Protein p53
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Doxorubicin
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Caspase 9