Cho Sung Gook, Sihn Choong-Ryoul, Yoo Soon Ji, Cho Kwang Keun, Lee Hong-Gu, Choi Yun-Jaie, Kim Sang Hoon
Department of Biology, Kyung Hee University, 130-701 Seoul, Republic of South Korea.
Cancer Lett. 2006 Sep 8;241(1):110-7. doi: 10.1016/j.canlet.2005.10.015. Epub 2005 Dec 9.
Microtubules are important cytoskeletal elements that have been shown to play a major role in many cellular processes because of their mechanical properties and/or their participation in various cell signaling pathways. Nocodazole is used as an effective microtubule-disrupting agent, and many recent studies have used it for the activation of spindle checkpoint. In this study, we sought to identify the potential nocodazole target genes by profiling the gene expression pattern in HeLa cells. When treated with 0.1ug/ml of nocodazole, cells were efficiently arrested in the mitotic phase. HeLa cells also showed a higher proportion of apoptosis after drug treatment for a prolonged period. By DNA chip assay, we discovered that 50 genes changed their expressions in the nocodazole-treated cells with a minimal 2.0-fold change at 18h post-treatment. The majority of the differentially expressed genes belonged to two functional groups--genes involved in transcription regulation and in cellular signaling. These observations could have significant implications for our understanding of the physiological and pathophysiological regulation of spindle disrupting agents in human cells.
微管是重要的细胞骨架成分,由于其机械特性和/或参与各种细胞信号通路,已被证明在许多细胞过程中发挥主要作用。诺考达唑用作有效的微管破坏剂,最近许多研究将其用于纺锤体检查点的激活。在本研究中,我们试图通过分析HeLa细胞中的基因表达模式来鉴定潜在的诺考达唑靶基因。用0.1μg/ml诺考达唑处理时,细胞有效地停滞在有丝分裂期。药物处理较长时间后,HeLa细胞也显示出更高比例的凋亡。通过DNA芯片分析,我们发现50个基因在诺考达唑处理的细胞中表达发生变化,在处理后18小时最小变化倍数为2.0倍。大多数差异表达基因属于两个功能组——参与转录调控和细胞信号传导的基因。这些观察结果可能对我们理解人类细胞中纺锤体破坏剂的生理和病理生理调节具有重要意义。