1. ¹Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba Science City, Ibaraki 305-8575, Japan
2. ²Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
3. ³Department of Hematology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
4. ⁴Department of Tumour Genetics (B-030), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg 69120, Germany

Correspondence: M Miwa, E-mail: m-miwa@md.tsukuba.ac.jp

Received 11 June 2003; Revised 5 August 2003; Accepted 25 August 2003; Published online 1 December 2003.

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.