Sugihara Eiji, Kanai Masayuki, Matsui Akira, Onodera Masafumi, Schwab Manfred, Miwa Masanao
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.
Oncogene. 2004 Jan 29;23(4):1005-9. doi: 10.1038/sj.onc.1207216.
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.
中心体在细胞极性、细胞周期调控和染色体稳定性方面发挥着重要作用。中心体异常在许多癌症中经常出现，并通过有丝分裂期间多极或单极纺锤体的组装导致子细胞中的染色体不稳定（包括非整倍体、四倍体和/或微核）。最近有报道称，肿瘤抑制基因的缺失或癌基因的过表达会导致中心体过度扩增。在一小部分神经母细胞瘤中发现了MYCN癌基因的扩增和过表达。在本研究中，我们检测了MYCN的过表达是否会导致神经母细胞瘤细胞中的中心体过度扩增。我们发现，在神经母细胞瘤细胞系中单独异位表达MYCN不会导致中心体过度扩增。然而，DNA损伤后这些细胞中出现了中心体过度扩增和微核形成。这些发现表明，MYCN的过表达消除了DNA损伤后中心体周期的调控。
