Modulation of Cellular Genes by Oncogenes

This chapter discusses the modulation of cellular genes by oncogenes. Recently, the investigation of the modulation of gene expression by retroviral and cellular oncogenes has begun. The chapter emphasizes the commonality of approach of the two groups and shows that different oncogenes may have remarkably similar (supplementary) effects as well as complementary effects. By focusing directly on the way oncogenes modulate the expression of cellular genes, more investigation in this important area of research can be stimulated. As examples, a cytoplasmic oncogene (ras), a nuclear oncogene (fos), and a nuclear oncogene derived from a DNA virus (adenovirus E 1A) were chosen for this investigation. Three mammalian ras protooncogenes and a related gene R-ras have been identified. The three protooncogenes are highly homologous, share a common introdexon motif, encode similar 21-kDa proteins (p21), and probably have evolved from a common ancestor. R-ras protein is predicted to be 55% homologous to H-ras p21 and to contain 236 amino acids; the introdexon organization of R-ras also differs from other members of the ras family. fos protein is localized in the nucleus, probably complexed to at least one other protein (p39) and perhaps DNA. Many external signals stimulate a transient burst of fos mRNA synthesis; epidermal growth factor, nerve growth factor, or platelet-derived growth factor, cAMP, TPA (the phorbol ester), vitamin D₃, ras protein, and thyrotropin all stimulate fos expression in different cell types.