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

研究成果: Contribution to journalArticle査読

84 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)5281-5290
ページ数10
ジャーナルOncogene
19
46
DOI
出版ステータス出版済み - 11 2 2000

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 遺伝学
  • 癌研究

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