A possible role for centrosome overduplication in radiation-induced cell death

Norihiro Sato, Kazuhiro Mizumoto, Masafumi Nakamura, Hikaru Ueno, Yohji A. Minamishima, John L. Farber, Masao Tanaka

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

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 γ-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 p21(Waf1/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.

Original languageEnglish
Pages (from-to)5281-5290
Number of pages10
JournalOncogene
Volume19
Issue number46
Publication statusPublished - 2000 Nov 2

Fingerprint

Centrosome
Cell Death
Radiation
Ionizing Radiation
Radiation Dosage
Neoplasms
Tumor Cell Line
Radiotherapy
Chromosomes
Cell Line

Keywords

  • Apoptosis
  • Centrosome
  • Ionizing radiation
  • Mitotic cell death
  • Multinucleated cells
  • p21(Waf1/Cip1)

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Sato, N., Mizumoto, K., Nakamura, M., Ueno, H., Minamishima, Y. A., Farber, J. L., & Tanaka, M. (2000). A possible role for centrosome overduplication in radiation-induced cell death. Oncogene, 19(46), 5281-5290.

A possible role for centrosome overduplication in radiation-induced cell death. / Sato, Norihiro; Mizumoto, Kazuhiro; Nakamura, Masafumi; Ueno, Hikaru; Minamishima, Yohji A.; Farber, John L.; Tanaka, Masao.

In: Oncogene, Vol. 19, No. 46, 02.11.2000, p. 5281-5290.

Research output: Contribution to journalArticle

Sato, N, Mizumoto, K, Nakamura, M, Ueno, H, Minamishima, YA, Farber, JL & Tanaka, M 2000, 'A possible role for centrosome overduplication in radiation-induced cell death', Oncogene, vol. 19, no. 46, pp. 5281-5290.
Sato N, Mizumoto K, Nakamura M, Ueno H, Minamishima YA, Farber JL et al. A possible role for centrosome overduplication in radiation-induced cell death. Oncogene. 2000 Nov 2;19(46):5281-5290.
Sato, Norihiro ; Mizumoto, Kazuhiro ; Nakamura, Masafumi ; Ueno, Hikaru ; Minamishima, Yohji A. ; Farber, John L. ; Tanaka, Masao. / A possible role for centrosome overduplication in radiation-induced cell death. In: Oncogene. 2000 ; Vol. 19, No. 46. pp. 5281-5290.
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