title: Enhanced expression of MYCN leads to centrosome hyperamplification after DNA damage in neuroblastoma cells.
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.
authors.affiliation: 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.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sugihara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kanai
authors.forename: Akira
authors.initials: A
authors.lastname: Matsui
authors.forename: Masafumi
authors.initials: M
authors.lastname: Onodera
authors.forename: Manfred
authors.initials: M
authors.lastname: Schwab
authors.forename: Masanao
authors.initials: M
authors.lastname: Miwa
mesh_terms: D018385:Centrosome; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics / Q000648:ultrastructure*; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D008164:Luminescent Proteins; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins