chapter  7
32 Pages

Expression of Oncogenes and Tumor Suppressor Genes in Teleost Fishes

The transfonnation of a nonnal cell into a cancer cell is a complex, multistep process. Two classes of genes are postulated to play important roles in this process: the oncogenes and the tumor suppressor genes. Both were named for their putative involvement in tumorigenesis; however, their true functions are key to the regulation of nonnal cellular growth. Moreover, it is their aberrant activity that has attracted so much attention. Though their presence was hypothesized much earlier,' oncogenes were first identified in 1976 as the transfonning genes of retroviruses, which incorporated these cellular sequences from their host genomes.2 The existence of suppressor genes, first implied by the familial genetic studies of Knudson,3 was confinned with the in vitro somatic cell hybrid experiments of Stanbridge and co-workers via the fusion of nonnal cells with malignant tumor cells.4 The hybrid cells typically contained the nonnal chromosome complements and, most importantly, exhibited the phenotype of the normal parent cell. Conversely, when fusions were made using cells deficient in specific chromosomes (i.e., 11 and 14), the resulting hybrids exhibited the malignant phenotype. Thus, it was correctly interpreted that the malignant phenotype was produced by defects or losses of genes necessary for nonnal cell

growth and function. Originally termed "recessive oncogenes," these are now more commonly referred to as "tumor suppressor genes."