Boylan M O, Zarbl H
Division of Toxicology, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
J Cell Biochem. 1991 Jul;46(3):199-205. doi: 10.1002/jcb.240460303.
Much has been learned about the molecular basis of cancer from the study of the dominantly acting viral and cellular oncogenes and their normal progenitors, the proto-oncogenes. More recent studies have resulted in the isolation and characterization of several genes prototypic of a second class of cancer genes. Whereas oncogenes act to promote the growth of cells, members of this latter class of genes act to inhibit cellular growth and are believed to contribute to the tumorigenic phenotype only when their activities are absent. This new class of cancer genes is referred to by a number of different names including; anti-oncogenes, recessive oncogenes, growth suppressor genes, tumor suppressor genes and emerogenes. Although only a few of these cancer genes have been identified, to date, it is likely that many additional genes of this class await identification. A third class of genes, necessary for the development of the cancer phenotype, is comprised of the transformation effector genes. These are normal cellular genes that encode proteins that cooperate with or activate oncogene functions and thereby induce the development of the neoplastic phenotype. The inactivation of transformation effector functions would therefore inhibit the ability of certain dominantly acting oncogenes to transform cells. The approaches outlined here describe functional assays for the isolation and molecular characterization of transformation effector and suppressor genes.
通过对具有显性作用的病毒癌基因和细胞癌基因及其正常前身原癌基因的研究,人们对癌症的分子基础已有了很多了解。最近的研究已导致分离和鉴定出几类属于第二类癌症基因的原型基因。原癌基因的作用是促进细胞生长,而后者这类基因的成员则起到抑制细胞生长的作用,并且只有当它们的活性缺失时才被认为会导致肿瘤发生表型。这类新的癌症基因有许多不同的名称,包括:抗癌基因、隐性癌基因、生长抑制基因、肿瘤抑制基因和应急基因。尽管迄今为止只鉴定出了少数这类癌症基因,但很可能还有许多这类基因有待鉴定。第三类对癌症表型发展必不可少的基因,由转化效应基因组成。这些是正常的细胞基因,它们编码的蛋白质与癌基因功能协同作用或激活癌基因功能,从而诱导肿瘤表型的发展。因此,转化效应功能的失活将抑制某些具有显性作用的癌基因转化细胞的能力。这里概述的方法描述了用于分离和分子鉴定转化效应基因和抑制基因的功能测定法。