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DNA-damaging drug-induced apoptosis sensitized by N-myc in neuroblastoma cells

Authors

  • Tai Li,

    1. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, Peoples Republic of China
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  • Lin Wang,

    1. Beijing EntryExit Inspection and Quarantine Bureau, Beijing, Peoples Republic of China
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  • Xiao-Xue Ke,

    1. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, Peoples Republic of China
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  • Xue-Yang Gong,

    1. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, Peoples Republic of China
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  • Jian-Hua Wan,

    1. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, Peoples Republic of China
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  • Xiang-wei Hao,

    1. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, Peoples Republic of China
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  • Man Xu,

    1. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, Peoples Republic of China
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  • Zonghuai Xiang,

    1. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, Peoples Republic of China
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  • Zhao-Bo Cui,

    Corresponding author
    1. Department of Respiratory and Critical Care Medicine, Harrison International Peace Hospital, Affiliated Hospital, Hebei Medical University, Hebei Province, Peoples Republic of China
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  • Hongjuan Cui

    Corresponding author
    1. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, Peoples Republic of China
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Correspondence may be addressed to either of these authors (email cuizhaobo@yahoo.com.cn or hcui@swu.edu.cn).

Abstract

Neuroblastoma is one of the most common solid tumours in children (8–10% of all malignancies). Over 22% of cases have N-myc amplification associated with aggressively growing neuroblastomas. Oncogene-induced sensitization of cells to apoptosis is an important mechanism for suppression of tumorigenesis. Tumour suppressors often play a critical role in linking oncogenes to apoptotic machinery. For example, activated p53 then targets both intrinsic and extrinsic pathways to promote apoptosis through transcription-dependent and -independent mechanisms. Understanding of the involved mechanisms has important clinical implications. We have employed DNA-damaging drug-induced apoptosis sensitized by oncogene N-myc as a model. DNA damaging drugs trigger high levels of p53, leading to caspase-9 activation in neuroblastoma cells. Inactivation of p53 protects cells from drug-triggered apoptosis sensitized by N-myc. These findings thus define a molecular pathway for mediating DNA-damaging drug-induced apoptosis sensitized by oncogene, and suggest that inactivation of p53 or other components of this apoptotic pathway may confer drug resistance in neuroblastoma cells. The data also suggests that inactivation of apoptotic pathways through co-operating oncogenes may be necessary for the pathogenesis of neuroblastoma with N-myc amplification.

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