Lopes Carla S, Sunkel Claudio E
Laboratório de Genética Molecular, Universidade do Porto, Portugal.
Arch Med Res. 2003 May-Jun;34(3):155-65. doi: 10.1016/S0188-4409(03)00024-9.
Faithful chromosome segregation during each cell division is regulated by the spindle checkpoint. This surveillance mechanism monitors kinetochore-microtubule attachment and the integrity of the mitotic apparatus, delaying mitotic exit until all chromosomes are properly aligned at the metaphase plate. Failure of this mechanism can generate gross aneuploidy. Since its discovery, mutations in genes involved in the spindle checkpoint response were predicted to be serious candidates for the chromosomal instability phenotype observed in many tumors. During the last few years, significant advances have been made in understanding the molecular basis of the spindle checkpoint. However, many studies of tumor cell lines and primary cancer isolates have failed to show a direct correlation with mutations in spindle checkpoint components. Nevertheless, it was shown that many tumor cells have an abnormal spindle checkpoint. Therefore, better understanding of the molecular mechanisms involved in regulation of spindle checkpoint response are expected to provide important clues regarding the mechanisms underlying the emergence of neoplasia.
纺锤体检查点调控着每次细胞分裂过程中染色体的忠实分离。这种监测机制会监控动粒-微管附着以及有丝分裂装置的完整性，延迟有丝分裂退出，直到所有染色体在中期板上正确排列。该机制失灵会导致严重的非整倍体现象。自发现以来，参与纺锤体检查点反应的基因中的突变被认为是许多肿瘤中观察到的染色体不稳定表型的重要候选因素。在过去几年中，在理解纺锤体检查点的分子基础方面取得了重大进展。然而，许多对肿瘤细胞系和原发性癌症分离株的研究未能显示出与纺锤体检查点成分突变的直接关联。尽管如此，已表明许多肿瘤细胞具有异常的纺锤体检查点。因此，更好地理解参与纺锤体检查点反应调控的分子机制有望为肿瘤形成的潜在机制提供重要线索。
