Shin Hyun Jin, Baek Kwan Hyuck, Jeon Ae Hwa, Park Moon Taek, Lee Su Jae, Kang Chang Mo, Lee Hyun Sook, Yoo Seong Ho, Chung Doo Hyun, Sung Young Chul, McKeon Frank, Lee Chang Woo
Research Institute, National Cancer Center, Goyang, Gyeonggi, 411-764, Korea.
Cancer Cell. 2003 Dec;4(6):483-97. doi: 10.1016/s1535-6108(03)00302-7.
In this study, we show that the formation of polyploidy following sustained mitotic checkpoint activation appears to be preceded by the ubiquitin-dependent proteolysis of hBubR1. In addition, the level of hBubR1 is significantly reduced not only in polyploid cells created by sustained mitotic spindle damage, but also in 21 (31.3%) of 67 human colon adenocarcinomas tested. Importantly, the introduction of hBubR1 triggers the apoptosis of polyploid cells formed by aberrant exit from mitosis and inhibits the growth of tumors established with these cells in athymic nude mice. These results suggest that hBubR1-mediated apoptosis prevents the propagation of cells that breach the mitotic checkpoint and that the control of hBubR1 protein level is an important factor in the acquisition of preneoplastic polyploidy.
在本研究中，我们发现持续的有丝分裂检查点激活后多倍体的形成似乎先于hBubR1的泛素依赖性蛋白水解。此外，hBubR1的水平不仅在由持续的有丝分裂纺锤体损伤产生的多倍体细胞中显著降低，而且在测试的67例人类结肠腺癌中的21例（31.3%）中也显著降低。重要的是，引入hBubR1会触发因异常退出有丝分裂而形成的多倍体细胞的凋亡，并抑制用这些细胞在无胸腺裸鼠中建立的肿瘤的生长。这些结果表明，hBubR1介导的凋亡可防止突破有丝分裂检查点的细胞增殖，并且hBubR1蛋白水平的控制是肿瘤前期多倍体形成的一个重要因素。
