Yeung Raymond S
Department of Surgery, University of Washington, Seattle, Washington, USA.
Genes Chromosomes Cancer. 2003 Dec;38(4):368-75. doi: 10.1002/gcc.10256.
Soon after proposing the "two-hit" hypothesis for tumorigenesis, Knudson pursued further experimental validation of the concept by using a rat model of dominantly inherited renal tumor. Today, the Eker rat is one of the best characterized models of tuberous sclerosis complex (TSC) and has been used extensively for study of the function of the TSC2 tumor suppressor gene. Along with TSC1, these two genes behave as expected for tumor suppressor genes with evidence for loss of heterozygosity in tumors and suppression of growth when expressed in proliferating cells. Despite much experimental work, the mechanisms of these genes have remained elusive until recently. This review summarizes some of the current concepts in our understanding of the biological and biochemical function of the TSC genes.
在提出肿瘤发生的“两次打击”假说后不久，克努森通过使用显性遗传肾肿瘤的大鼠模型，对这一概念进行了进一步的实验验证。如今，埃克大鼠是结节性硬化症复合体（TSC）特征最明确的模型之一，并已广泛用于研究TSC2肿瘤抑制基因的功能。与TSC1一起，这两个基因表现出肿瘤抑制基因所预期的特性，有证据表明肿瘤中杂合性缺失，且在增殖细胞中表达时可抑制生长。尽管进行了大量实验工作，但直到最近，这些基因的作用机制仍不清楚。本综述总结了目前我们对TSC基因生物学和生化功能理解中的一些概念。
