title: p16 Gene Transfer Induces Centrosome Amplification and Abnormal Nucleation Associated with Survivin Downregulation in Glioma Cells.
abstract: OBJECTIVE
  In human glioma cells, p16 gene transfer induced G1/S arrest, increased radiosensitivity and abnormal nucleation (especially bi- and multinucleation). Survivin suppression caused G2/M arrest, radiosensitization and an increase in aneuploidy accompanied by centrosome amplification. Abnormal nucleation and aneuploidy represent chromosome instability (CIN), and it is well known that centrosome amplification leads to CIN. However, little has been reported that suggests that transferring p16 causes centrosome overduplication during the G1/S phase.
  
  
  METHODS
  The p16 gene was transferred into p16-null human glioma cell lines (U251MG and D54MG) using adenovirus with or without irradiation. Centrosome amplification was evaluated by immunofluorescence. We also investigated the DNA replication licensing factor CDT1, its inhibitor geminin and survivin expression as regulators of chromosomal segregation.
  
  
  RESULTS
  p16 gene transfer with radiation initiated the greatest degree of centrosome overduplication. CDT1 showed low levels, geminin was unchanged and survivin decreased in Ax-hp16-infected cells with radiation. Those changes of factors affecting DNA licensing or chromosomal segregation might contribute to CIN.
  
  
  CONCLUSIONS
  p16 transfer caused centrosome amplification even in G1/S phase-arrested cells. This suggests that p16 is involved in abnormal nucleation and radiosensitization in human glioma cells. © 2015 S. Karger AG, Basel.
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takayasu
authors.forename: Seiji
authors.initials: S
authors.lastname: Hama
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yamasaki
authors.forename: Taiichi
authors.initials: T
authors.lastname: Saito
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Ryo
authors.initials: R
authors.lastname: Nosaka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu