RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer
RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer
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DOI：
10.1038/sj.onc.1205834
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发表时间：
2002-10-07
期刊：
影响因子：
8
通讯作者：
Kaye, FJ
中科院分区：
文献类型：
--
作者：
Kaye, FJ
Rb：CDK：Cyclin：p16抑癌通路的遗传成分在多种人类肿瘤中经历了突变和表观遗传学的改变，是几种DNA肿瘤病毒转化癌蛋白失活的关键靶点。肺癌是这些研究的一个有用的模型系统，因为它是第一个证明Rb在常见成人恶性肿瘤的发生中发挥重要作用的肿瘤，也是第一个证明多组分Rb：p16肿瘤抑制通路的遗传学证据的人类癌症。然而，肺肿瘤的发生是一个复杂的疾病过程，需要长期接触致癌物才能在许多不同的遗传位点获得体细胞变化。了解Rb调节细胞增殖、分化和凋亡的多功能特性以及它们如何与其他克隆性基因缺陷的顺序积累相关，对于了解在不同亚型肺癌中观察到的基因失活的特定模式和实现分子靶向治疗的前景是至关重要的。
The genetic components of the RB:CDK:cyclin:p16 tumor suppressor pathway undergo mutational and epigenetic alterations in a wide range of human cancers and serve as critical targets for inactivation by the transforming oncoproteins of several DNA tumor viruses. Lung cancer has been a useful model system for these studies as it was the first tumor to demonstrate an important role for RB in the genesis of a common adult malignancy and was also the first human cancer to demonstrate genetic evidence for a multi-component RB:p16 tumor suppressor pathway. Lung tumorigenesis, however, is a complex disease process that requires longstanding carcinogen exposure in order to acquire somatic alterations at many distinct genetic loci. Understanding the multifunctional properties of RB to regulate cell proliferation, differentiation, and apoptosis and how they relate to the sequential accumulation of other clonal gene defects will be essential in order to understand the specific patterns of gene inactivation observed in different subtypes of lung cancer and to fulfill the promise of 'molecular target' therapeutics.