Correlation between centrosome abnormalities and chromosomal instability in human pancreatic cancer cells
Correlation between centrosome abnormalities and chromosomal instability in human pancreatic cancer cells
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DOI：
10.1016/s0165-4608(00)00384-8
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发表时间：
2001-04-01
影响因子：
--
通讯作者：
Tanaka, M
中科院分区：
文献类型：
--
作者：
Sato, N;Mizumoto, K;Tanaka, M
染色体不稳定性是人类癌症的常见特征，其特征是染色体的数量或结构异常，但这些变化背后的机制仍不清楚。由于中心体在有丝分裂过程中平衡染色体分离中起着关键作用，我们试图研究大量人胰腺癌细胞系中中心体异常和染色体不稳定性之间的关系。免疫荧光显微镜显示，在大多数细胞系中，中心体的大小、形状和数量都非常不典型。这些异常的中心体有助于多极纺锤体的组装，导致有丝分裂缺陷和染色体的错误分离。有趣的是，中心体缺陷的高频率与培养中细胞的生长速率呈负相关。荧光原位杂交结果显示，中心体缺陷的细胞系中染色体数目发生了显著的变化。此外，中心体缺陷的水平和染色体不平衡的水平之间存在显着的正相关。这些结果表明，中心体异常可导致纺锤体解体和染色体分离错误，这可能会导致染色体变异的积累。因此。中心体功能缺陷：可能是人类胰腺癌遗传不稳定的根本原因。(C)2001 Elsevier Science Inc. All rights reserved.
Chromosomal instability, characterized by abnormal numbers or structures of chromosomes, is a common feature of human cancers, but the mechanisms behind these changes are still unclear. Since centrosomes play a pivotal role in balanced chromosomal segregation during mitosis, we attempted to investigate the association between centrosorne abnormalities and chromosomal instability in a large number of human pancreatic cancer cell lines. Immunofluorescence microscopy revealed centrosomes that were highly atypical with respect to their size, shape, and number in most cell lines. These abnormal centrosomes contributed to the assembly of multipolar spindles, resulting in defective mitosis and chromosome mis-segregation. Interestingly, a high frequency of centrosome defects inversely correlated with the growth rate of cells in culture. Fluorescence in situ hybridization revealed a dramatic variation of chromosome numbers in cell lines with the defective centrosome phenotype. Furthermore, a significant positive correlation existed between the level of centrosome defects and the level of chromosomal imbalances. These results indicate that centrosome abnormalities can lead to spindle disorganization and chromosome segregation errors, which may drive the accumulation of chromosomal alterations. Thus. defects in centrosome function ma!: be an underlying cause of genetic instability in human pancreatic cancers. (C) 2001 Elsevier Science Inc. All rights reserved.