Roles of growth factor activities in oncogenesis.

I NSIGHT into normal and abnormal cell growth and differentiation may be obtained by identifying and analyzing the activity of highly specific genes, called oncogenes, whose coding sequences contain the information necessary to initiate and maintain neoplastic transformation. The identification of oncogenes and the characterization of the structure and function of these genes have progressed rapidly in the last few years.’3 Oncogenes were first recognized in acutetransforming viruses capable of mediating in vitro and in vivo cellular transformation. It was subsequently appreciated that the viral oncogenes were acquired from normal host genes (proto-oncogenes) of infected cells by genetic transduction.4 The host proto-oncogenes from which the viral oncogenes originated are highly conserved genes in evolution and are expressed in many different tissues.7’#{176} The finding of protooncogenes in normal cells has established the highly significant potential for malignant transformation in higher species by activation of proto-oncogenes, and subsequently led to the discovery of activated cellular oncogenes by DNA-mediated gene transfer (transfection).#{176} #{176} Cellular proto-oncogenes may contribute to malignant transformation when somatic mutation leads to expression at inappropriate times,tt in increased amounts,’2 or in abnormal forms,’3 by mechanisms including gene amplification, point mutation, or transposition. These relationships are depicted in Fig 1 . In this review, we will use the term viral oncogene (v-onc) to mean a transforming gene of a tumor-inducing virus and proto-oncogene to mean a normal cellular gene that, when inappropriately activated by mutations, gives rise to a cellular oncogene (c-onc) that has the potential to mediate cellular transformation and tumorigenesis.2