Fukasawa Kenji
Molecular Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Biochim Biophys Acta. 2008 Sep;1786(1):15-23. doi: 10.1016/j.bbcan.2008.04.002. Epub 2008 Apr 22.
Centrosomes play a critical role in formation of bipolar mitotic spindles, an essential event for accurate chromosome segregation into daughter cells. Numeral abnormalities of centrosomes (centrosome amplification) occur frequently in cancers, and are considered to be the major cause of chromosome instability, which accelerates acquisition of malignant phenotypes during tumor progression. Loss or mutational inactivation of p53 tumor suppressor protein, one of the most common mutations found in cancers, results in a high frequency of centrosome amplification in part via allowing the activation of the cyclin-dependent kinase (CDK) 2-cyclin E (as well as CDK2-cyclin A) which is a key factor for the initiation of centrosome duplication. In this review, the role of centrosome amplification in tumor progression, and mechanistic view of how centrosomes are amplified in cells through focusing on loss of p53 and aberrant activities of CDK2-cyclins will be discussed.
中心体在双极有丝分裂纺锤体的形成中起着关键作用，这是染色体准确分离到子细胞中的一个重要事件。中心体的数量异常（中心体扩增）在癌症中频繁发生，被认为是染色体不稳定的主要原因，而染色体不稳定会加速肿瘤进展过程中恶性表型的获得。p53肿瘤抑制蛋白的缺失或突变失活是癌症中最常见的突变之一，部分原因是通过激活细胞周期蛋白依赖性激酶（CDK）2-细胞周期蛋白E（以及CDK2-细胞周期蛋白A）导致中心体扩增频率升高，而CDK2-细胞周期蛋白E是启动中心体复制的关键因素。在这篇综述中，将讨论中心体扩增在肿瘤进展中的作用，以及通过关注p53缺失和CDK2-细胞周期蛋白的异常活性，细胞中中心体如何扩增的机制观点。
