Hartwell L H, Kastan M B
Department of Genetics, University of Washington, Seattle 98195.
Science. 1994 Dec 16;266(5192):1821-8. doi: 10.1126/science.7997877.
Multiple genetic changes occur during the evolution of normal cells into cancer cells. This evolution is facilitated in cancer cells by loss of fidelity in the processes that replicate, repair, and segregate the genome. Recent advances in our understanding of the cell cycle reveal how fidelity is normally achieved by the coordinated activity of cyclin-dependent kinases, checkpoint controls, and repair pathways and how this fidelity can be abrogated by specific genetic changes. These insights suggest molecular mechanisms for cellular transformation and may help to identify potential targets for improved cancer therapies.
在正常细胞演变成癌细胞的过程中会发生多种基因变化。癌细胞中基因组复制、修复和分离过程中保真度的丧失促进了这种演变。我们对细胞周期理解的最新进展揭示了细胞周期蛋白依赖性激酶、检查点控制和修复途径的协同活动通常是如何实现保真度的,以及这种保真度如何因特定的基因变化而被破坏。这些见解揭示了细胞转化的分子机制,并可能有助于确定改进癌症治疗方法的潜在靶点。