Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

T Saito; S Hama; H Izumi; F Yamasaki; Y Kajiwara; S Matsuura; K Morishima; T Hidaka; P Shrestha; K Sugiyama; K Kurisu

doi:10.1038/sj.bjc.6604160

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Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

Journal article

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Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

T Saito, S Hama, H Izumi, F Yamasaki, Y Kajiwara, S Matsuura, K Morishima, T Hidaka, P Shrestha, K Sugiyama, …

British journal of cancer, Vol.98(2), pp.345-355

01/29/2008

DOI: 10.1038/sj.bjc.6604160

PMCID: PMC2361434

PMID: 18195712

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Abstract

Glioblastoma is characterised by invasive growth and a high degree of radioresistance. Survivin, a regulator of chromosome segregation, is highly expressed and known to induce radioresistance in human gliomas. In this study, we examined the effect of survivin suppression on radiosensitivity in malignant glioma cells, while focusing on centrosome aberration and chromosome instability (CIN). We suppressed survivin by small interfering RNA transfection, and examined the radiosensitivity using a clonogenic assay and a trypan blue exclusion assay in U251MG (p53 mutant) and D54MG (p53 wild type) cells. To assess the CIN status, we determined the number of centrosomes using an immunofluorescence analysis, and the centromeric copy number by fluorescence in situ hybridisation. As a result, the radiosensitisation differed regarding the p53 status as U251MG cells quickly developed extreme centrosome amplification (=CIN) and enhanced the radiosensitivity, while centrosome amplification and radiosensitivity increased more gradually in D54MG cells. TUNEL assay showed that survivin inhibition did not lead to apoptosis after irradiation. This cell death was accompanied by an increased degree of aneuploidy, suggesting mitotic cell death. Therefore, survivin inhibition may be an attractive therapeutic target to overcome the radioresistance while, in addition, proper attention to CIN (centrosome number) is considered important for improving radiosensitivity in human glioma.

Translational Therapeutics

Details

Title: Subtitle: Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells
Creators: T Saito - Hiroshima University
S Hama - Hiroshima University
H Izumi - Hiroshima University
F Yamasaki - Hiroshima University
Y Kajiwara - Hiroshima University
S Matsuura - Hiroshima University
K Morishima - Hiroshima University
T Hidaka - Hiroshima University
P Shrestha - Hiroshima University
K Sugiyama - Hiroshima University
K Kurisu - Hiroshima University
Resource Type: Journal article
Publication Details: British journal of cancer, Vol.98(2), pp.345-355
DOI: 10.1038/sj.bjc.6604160
PMID: 18195712
PMCID: PMC2361434
NLM abbreviation: Br J Cancer
ISSN: 0007-0920
eISSN: 1532-1827
Publisher: Nature Publishing Group
Alternative title: Survivin suppression and centrosome amplification
Language: English
Date published: 01/29/2008
Academic Unit: Neurosurgery
Record Identifier: 9984695680802771

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