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Enhanced expression of MYCN leads to centrosome hyperamplification after DNA damage in neuroblastoma cells

Oncogene volume 23, pages 1005–1009 (2004)Cite this article

Abstract

Centrosomes play important roles in cell polarity, regulation of cell cycle and chromosomal stability. Centrosome abnormality is frequently found in many cancers and contributes to chromosomal instability (including aneuploidy, tetraploidy, and/or micronuclei) in daughter cells through the assembly of multipolar or monopolar spindles during mitosis. It has recently been reported that loss of tumor suppressor genes or overexpression of oncogenes causes centrosome hyperamplification. Amplification and overexpression of the MYCN oncogene is found in a subgroup of neuroblastomas. In this study, we examined whether overexpression of MYCN causes centrosome hyperamplification in neuroblastoma cells. We show that ectopic expression of MYCN alone in a neuroblastoma cell line did not cause centrosome hyperamplification. However, centrosome hyperamplification and micronuclei formation were seen in these cells after DNA damage. These findings suggest that overexpression of MYCN abrogates the regulation of the centrosome cycle after DNA damage.

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Acknowledgements

This work was supported in part by grant-in-aids for Cancer Research from the Ministry of Health, Labour and Welfare (Japan) and the Japan Society for the Promotion of Sciences (Japan). We thank Dr H Saya (Kumamoto University) for a valuable suggestion. We thank S Hanai, N Uematsu, S Ohashi, Y Nogi and A Kabayama for precious comments and technical assistance.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba Science City, Ibaraki, 305-8575, Japan

    Eiji Sugihara, Masayuki Kanai & Masanao Miwa

  2. Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

    Akira Matsui

  3. Department of Hematology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

    Masafumi Onodera

  4. Department of Tumour Genetics (B-030), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Manfred Schwab

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  1. Eiji Sugihara
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  2. Masayuki Kanai
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  4. Masafumi Onodera
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Correspondence to Masanao Miwa.

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Sugihara, E., Kanai, M., Matsui, A. et al. Enhanced expression of MYCN leads to centrosome hyperamplification after DNA damage in neuroblastoma cells. Oncogene 23, 1005–1009 (2004). https://doi.org/10.1038/sj.onc.1207216

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