Centrosome defects and genetic instability in malignant tumors.
Centrosome defects and genetic instability in malignant tumors.
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发表时间：
1998-09
期刊：
影响因子：
11.2
通讯作者：
G. Pihan;A. Purohit;Janice E. Wallace;H. Knecht;B. Woda;P. Quesenberry;S. Doxsey
中科院分区：
文献类型：
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作者：
G. Pihan;A. Purohit;Janice E. Wallace;H. Knecht;B. Woda;P. Quesenberry;S. Doxsey
遗传不稳定性是许多人类癌症的共同特征。这种情况的特征通常是染色体数目异常，尽管对产生这种改变的遗传状态的机制知之甚少。一种可能性是染色体在有丝分裂过程中由于功能失调的有丝分裂纺锤体的组装而错误分离。由于中心体参与了纺锤体的组装，它们可能通过异常纺锤体的组织而导致染色体的错误分离。作为这个想法的初步测试，我们使用中心体蛋白pericentrin的抗体检查恶性肿瘤的中心体异常。我们发现几乎所有肿瘤和肿瘤源性细胞系的中心体在形状、大小和组成上都是非典型的，并且通常以多个拷贝存在。此外，几乎所有的着丝粒周围染色的结构在肿瘤细胞有核微管，他们参与形成混乱的有丝分裂纺锤体，染色体被错误分离。所有的肿瘤细胞系都有中心体缺陷和染色体数目异常，而在非肿瘤细胞中均未观察到。这些结果表明，中心体缺陷是恶性肿瘤的共同特征，并表明它们可能有助于癌症的遗传不稳定性。
Genetic instability is a common feature of many human cancers. This condition is frequently characterized by an abnormal number of chromosomes, although little is known about the mechanism that generates this altered genetic state. One possibility is that chromosomes are missegregated during mitosis due to the assembly of dysfunctional mitotic spindles. Because centrosomes are involved in spindle assembly, they could contribute to chromosome missegregation through the organization of aberrant spindles. As an initial test of this idea, we examined malignant tumors for centrosome abnormalities using antibodies to the centrosome protein pericentrin. We found that centrosomes in nearly all tumors and tumor-derived cell lines were atypical in shape, size, and composition and were often present in multiple copies. In addition, virtually all pericentrin-staining structures in tumor cells nucleated microtubules, and they participated in formation of disorganized mitotic spindles, upon which chromosomes were missegregated. All tumor cell lines had both centrosome defects and abnormal chromosome numbers, whereas neither was observed in nontumor cells. These results indicate that centrosome defects are a common feature of malignant tumors and suggest that they may contribute to genetic instability in cancer.