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Introduction

Oncogene volume 21, pages 6140–6145 (2002)Cite this article

Centrosomes have recently attracted considerable attention primarily because of their potential importance in carcinogenesis. Chromosome instability is a hallmark of virtually all solid cancers, being a formidable force that drives multi-step carcinogenesis: either loss or gain of a single chromosome can simultaneously introduce multiple mutations, which are responsible for acquisition of further malignant phenotypes. The presence of more than two centrosomes in a cell results in the formation of defective mitotic spindles directed by multiple spindle poles, which in turn increases the chromosome segregation errors. This potential role of centrosomes in chromosome instability, hence in cancer development, is by no means a new-sprung idea. It was initially proposed by Theodor Boveri (1914). In his book, The Origin of Malignant Tumors, he wrote, ‘malignant tumors might be the result of a certain abnormal condition of the chromosomes, which may arise from multipolar mitosis. Abnormal (multipolar) mitoses may bring about an immense number of different chromosome combinations, such combinations as would make a cell into a tumor cell must occasionally occur. The more the abnormal (multipolar) divisions that take place in a tissue, the greater of course is the probability that the necessary combination (of chromosomes to become malignant tumors) shall appear.’ This remarkable proposition had long been forgotten until several years ago. In the course of the study to identify the mechanism underlying extensive chromosome instability seen in mice deficient for p53 tumor suppressor, it was found that loss of p53 resulted in abnormal amplification of centrosomes (Fukasawa et al., 1996, 1997). This finding has been further corroborated by the studies using transgenic mice expressing the mutant p53 gene (Wang et al., 1998). Since p53 is the most frequently mutated gene in human cancer (Hollstein et al., 1991; Levine et al., 1991), it is reasonable to speculate that mutation of p53 at least in part promotes tumor progression via chromosome instability associated with centrosome amplification. Subsequently, it has been found that centrosome abnormality (numerical amplification as well as hypertrophy of centrosomes) is common in human cancer (Pihan et al., 1998; Lingle et al., 1998; Carroll et al., 1999), and these observations have fully resurrected Boveri's century old hypothesis (see D'Assoro et al., 2002).

The important issue to be discussed in the role of centrosomes in chromosome instability is the mechanistic aspect of how cells either gain or lose chromosomes due to the presence of an excess number of centrosomes. Although this is currently not completely understood and an area of active research, there are data to suggest at least two models:

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  1. Department of Cell Biology, University of Cincinnati College of Medicine, PO Box 670521, Cincinnati, 45267-0521, Ohio, OH, USA

    Kenji Fukasawa

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  1. Kenji Fukasawa
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Correspondence to Kenji Fukasawa.

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Fukasawa, K. Introduction. Oncogene 21, 6140–6145 (2002). https://doi.org/10.1038/sj.onc.1205771

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