Mondal Gourish, Sengupta Shiladitya, Panda Chinmoy K, Gollin Susanne M, Saunders William S, Roychoudhury Susanta
Human Genetics and Genomics Division, Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Kolkata-700 032, India.
Carcinogenesis. 2007 Jan;28(1):81-92. doi: 10.1093/carcin/bgl100. Epub 2006 Jun 15.
Defects in the spindle assembly checkpoint are thought to be responsible for an increased rate of aneuploidization during tumorigenesis. Despite a plethora of information on the correlation between BUB-MAD gene expression levels and defects in the spindle checkpoint, very little is known about alteration of another important spindle checkpoint protein, Cdc20, in human cancer and its role in tumor aneuploidy. We observed overexpression of CDC20 in several oral squamous cell carcinoma (OSCC) cell lines and primary head and neck tumors and provide evidence that such overexpression of CDC20 is associated with premature anaphase promotion, resulting in mitotic abnormalities in OSCC cell lines. We also reconstituted the chromosomal instability phenotype in a chromosomally stable OSCC cell line by overexpressing CDC20. Thus, abnormalities in the cellular level of Cdc20 may deregulate the timing of anaphase promoting complex (APC/C) in promoting premature anaphase, which often results in aneuploidy in the tumor cells.
纺锤体组装检验点缺陷被认为是肿瘤发生过程中非整倍体化率增加的原因。尽管关于BUB - MAD基因表达水平与纺锤体检验点缺陷之间的相关性已有大量信息，但对于另一种重要的纺锤体检验点蛋白Cdc20在人类癌症中的改变及其在肿瘤非整倍体中的作用却知之甚少。我们观察到CDC20在几种口腔鳞状细胞癌（OSCC）细胞系和原发性头颈部肿瘤中过表达，并提供证据表明CDC20的这种过表达与后期促进过早有关，导致OSCC细胞系出现有丝分裂异常。我们还通过过表达CDC20在染色体稳定的OSCC细胞系中重建了染色体不稳定表型。因此，Cdc20细胞水平的异常可能会在促进后期过早发生时失调后期促进复合体（APC/C）的时间，这通常会导致肿瘤细胞出现非整倍体。
