A possible role for centrosome overduplication in radiation-induced cell death
| Autor: | Masao Tanaka, John L. Farber, Masafumi Nakamura, Kazuhiro Mizumoto, Yohji A. Minamishima, Norihiro Sato, Hikaru Ueno |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Cyclin-Dependent Kinase Inhibitor p21 Male Cancer Research Programmed cell death Time Factors Cell Survival Centrosome cycle Apoptosis Spindle Apparatus Biology Transfection Adenoviridae Multinucleate Chromosome Segregation Cyclins Genetics Tumor Cells Cultured Humans Fluorescent Antibody Technique Indirect Molecular Biology Mitosis Cells Cultured Micronuclei Chromosome-Defective Cell Nucleus Centrosome Cell Death Cell Cycle Dose-Response Relationship Radiation Cell cycle Fibroblasts Flow Cytometry Cell biology Phenotype Gamma Rays Multipolar spindles |
| Zdroj: | Oncogene. 19(46) |
| ISSN: | 0950-9232 |
| Popis: | Radiotherapy plays a key role in the treatment of many tumors; however, the precise mechanisms responsible for radiation-induced cell death remain uncertain. We have reported previously that ionizing radiation induces centrosome overduplication in human tumor cells. The present study was designed to elucidate a possible link between centrosome dysregulation and radiation-induced cell death. Exposure to 10 Gy gamma-radiation resulted in a substantial increase in cells containing an abnormally high number of centrosomes in a variety of cell lines derived from different types of human solid tumors. These aberrant centrosomes contribute to the assembly of multipolar spindles, thereby causing an unbalanced division of chromosomes and mitotic cell death characterized by the appearance of multi- or micronucleated cells. An extensive analysis of a panel of 10 tumor cell lines revealed a positive correlation between the fraction of cells with multiple centrosomes and the fraction with these nuclear abnormalities after irradiation. When the centrosome overduplication was blocked by enforced expression of p21Waf1/Cip1, the radiation-induced lethality was drastically rescued. Taken together, these results indicate that centrosome overduplication may be a critical event leading to mitotic failure and subsequent cell death following exposure to ionizing radiation. |
| Databáze: | OpenAIRE |
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