文章基本信息

标题：Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint
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作者：Geert J. P. L. Kops ; Daniel R. Foltz ; Don W. Cleveland 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：23
页码：8699-8704
DOI：10.1073/pnas.0401142101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A compromised mitotic checkpoint, the primary mechanism for ensuring that each new cell receives one copy of every chromosome, has been implicated as a contributor to carcinogenesis. However, a checkpoint response is shown here to be essential for cell survival, including that of chromosomally instable colorectal cancer cells. Reducing the levels of the checkpoint proteins BubR1 or Mad2 in human cancer cells or inhibiting BubR1 kinase activity provokes apoptotic cell death within six divisions except when cytokinesis is also inhibited. Thus, suppression of mitotic checkpoint signaling is invariably lethal as the consequence of massive chromosome loss, findings that have implications for inhibiting proliferation of tumor cells.