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

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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.