Pitot H C
McArdle Laboratory for Cancer Research, Medical School, University of Wisconsin, Madison, WI 53706, USA.
J Cancer Res Clin Oncol. 1996;122(5):257-65. doi: 10.1007/BF01261401.
The alteration of genetic expression ubiquitously seen in both preneoplastic and neoplastic tissues has been investigated for many years in the hope that the critical molecular changes resulting in cancer can be elucidated. The alteration of the expression of specific genes has already been employed in diagnostic and even screening procedures for this disease. In the past many observations of such alterations have led to a variety of theories but not definitive generalizations. Studies of the alteration of genetic expression may now be viewed in the light of our understanding of the multistage nature of neoplastic development. This brief review describes a number of genes the expressions of which are altered during the stages of initiation and promotion, in contrast to the alteration of expression of genes during the stage of progression. The promotion stage is concerned primarily with the chronic interaction of promoting agents in the environment with the genetic apparatus of the cell, played out on the altered genetic background resulting from the stage of initiation. In contrast, the progression stage is characterized primarily by an evolving karyotypic instability resulting in continual genetic changes during this stage. On the basis of these distinctions it is possible to identify genes the altered expression of which is unique to the stage of progression. The identification of these genes and an understanding of mechanisms resulting in their altered expression will allow not only a better molecular characterization of the progression stage but also the quantitative analysis of neoplastic development in several model animal systems as well as eventually in the human.
在肿瘤前组织和肿瘤组织中普遍可见的基因表达改变已经被研究多年，以期能够阐明导致癌症的关键分子变化。特定基因表达的改变已被用于该疾病的诊断甚至筛查程序。过去，许多关于此类改变的观察结果引发了各种理论，但并未得出明确的一般性结论。现在，鉴于我们对肿瘤发生发展多阶段性质的理解，可以重新审视基因表达改变的研究。这篇简短的综述描述了一些基因，其表达在起始和促癌阶段发生改变，与进展阶段基因表达的改变形成对比。促癌阶段主要涉及环境中的促癌剂与细胞遗传机制的长期相互作用，这种相互作用发生在起始阶段所导致的改变了的遗传背景之上。相比之下，进展阶段的主要特征是核型不稳定性不断演变，导致在此阶段持续发生基因变化。基于这些差异，有可能识别出那些其表达改变在进展阶段独具特色的基因。识别这些基因并了解导致其表达改变的机制，不仅将有助于更好地从分子层面描述进展阶段，还能对几种模式动物系统以及最终对人类的肿瘤发生发展进行定量分析。
