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恶性蠕虫:癌症研究可从秀丽隐杆线虫中学到什么。

Malignant worms: what cancer research can learn from C. elegans.

作者信息

Saito R Mako, van den Heuvel Sander

机构信息

Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA.

出版信息

Cancer Invest. 2002;20(2):264-75. doi: 10.1081/cnv-120001153.

Abstract

Developmental processes in the nematode C. elegans are controlled by pathways of gene functions that are analogous to those used in mammals. Hence, genetic studies in C. elegans have helped build the frameworks for these regulatory pathways. Many homologs of human genes that are targets for mutation in cancer have been found to function at distinct steps within such genetic pathways. This way, studies in C. elegans have provided important clues about the functions of human oncogenes and tumor suppressors. Understanding how human cancer genes function and act in signaling cascades is of great importance. This information reveals what kind of molecular changes contribute to the process of cell transformation. Moreover, additional candidate oncogenes and tumor suppressors may be revealed by identifying the functional partners of genes with an established role in cancer. Furthermore, identifying a cascade of gene functions increases the number of potential targets for therapeutic intervention, as blocking either one of multiple genes may interfere with signal transduction through the pathway. Simultaneous approaches in a number of different model systems act synergistically in solving pathways of gene functions. By using multiple models, the field takes advantage of the strengths of each system and circumvents its limitations. As one of the most powerful genetic animal systems, C. elegans will continue to reveal new mammalian signaling components. In addition, now that the C. elegans genome sequence has been completed, an increasing number of researchers are likely to discover homologs of human disease genes in the nematode and to analyze gene function in the worm model. Combined with the great potential of this animal in drug screens, it is simple to predict that C. elegans will worm its way deeper and deeper into cancer research.

摘要

线虫秀丽隐杆线虫的发育过程由与哺乳动物所使用的基因功能途径相似的途径控制。因此,秀丽隐杆线虫的遗传学研究有助于构建这些调控途径的框架。许多在癌症中发生突变的人类基因同源物已被发现在此类遗传途径的不同步骤中发挥作用。通过这种方式,秀丽隐杆线虫的研究为人类癌基因和肿瘤抑制基因的功能提供了重要线索。了解人类癌症基因如何在信号级联反应中发挥作用至关重要。这些信息揭示了哪种分子变化促成了细胞转化过程。此外,通过鉴定在癌症中已确定起作用的基因的功能伙伴,可能会发现更多的候选癌基因和肿瘤抑制基因。此外,确定一系列基因功能会增加治疗干预的潜在靶点数量,因为阻断多个基因中的任何一个都可能干扰通过该途径的信号转导。在许多不同模型系统中同时采用的方法在解决基因功能途径方面具有协同作用。通过使用多种模型,该领域利用了每个系统的优势并规避了其局限性。作为最强大的遗传动物系统之一,秀丽隐杆线虫将继续揭示新的哺乳动物信号成分。此外,既然秀丽隐杆线虫的基因组序列已经完成,越来越多的研究人员可能会在这种线虫中发现人类疾病基因的同源物,并在蠕虫模型中分析基因功能。结合这种动物在药物筛选方面的巨大潜力,可以很容易地预测秀丽隐杆线虫将在癌症研究中越来越深入。

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