Involvement of Proto-Oncogenes in Growth Control: The Induction of c-fos and c-myc by Growth Factors

Abstract

One of the most conspicuous features of retroviral oncogenes is their impact on the growth control machinery of the target cell. For this reason, it has become a generally accepted idea that their normal cellular homologs, the proto-oncogenes, may have crucial physiological functions in metabolic pathways involved in the regulation of cellular proliferation. It was not until 1983 that this hypothesis was substantiated by the observation that two proto-oncogenes, c-sis and c-erbB, are part of the cellular growth factor receptor system (Doolittle et al. 1983; Waterfield et al. 1985; Downward et al. 1984) and articles by Heldin and Westermark; Schlessinger and Beng et al., this Vol.). At the same time, expression of a proto-oncogene encoding a nuclear protein, c-myc, was reported to increase rapidly following the treatment of different cell types with growth-inducing components (Kelly et al. 1983). This discovery was followed by the finding that c-myc mRNA accumulation is even preceded by the transcriptional activation of another proto-oncogene coding for a nuclear product, the c-fos gene (Greenberg and Ziff 1984; Cochran et al. 1984; Kruijer et al. 1984; Müller et al. 1984). This chapter discusses the results of these studies and several subsequent investigations analyzing the expression of c-fos and c-myc during cell proliferation. (For reviews of each of these proto-oncogenes, the reader is referred to Jenuwein and Müller, this Vol., and Mölling, this Vol.).