It is now more than 10 years since it was announced almost simultaneously by two groups of investigators that the sequence of the v&s-transforming oncogene was homologous to the sequence of the platelet-derived growth factor (PDGF)(Doolittle et al., 1983; Waterfield et al., 1983). Since then, several cell-derived oncogene products have been found to be homologs of growth factors, of growth factor receptors, or of molecules on the signal-transducing pathway of these receptors, the best known being v-Erb, re-Bated to the epidermal growth factor (EGF) receptor, and Ras (reviewed by Hunter, 1991). Since, in the last analysis, the growth of cells in vitro and in vivo is regulated by the environmental signals, among which growth factors figure prominently, it makes sense, in retrospect, forthe products of oncogenes to masquerade themselves as growth factor-related molecules. By making themselves into growth factors or receptors for growth factors, these oncogenes have, so to speak, taken the direct approach to transformation.

A more indirect but equally effective strategy would be for viral and nonviral oncogenes to alter the activity of growth factor receptors, their substrates, or their ligands either by regulating their expression or by altering their activity through direct binding to them. This could have rofound effect on cell growth, would not depend on the cooperation of a compliant RNA virus, and could be adapted to an endless variety of situations. Evidence has been accumulating recently that viral and nonviral oncogenes are using this second strategy, and although the evidence so far has been fragmentary, it extends to enough different oncogenes and different growth factors to suggest a pattern that is only awaiting further exploration. The starting point for our discussion is the observation that the overexpression of a number of growth factor receptors results in ligand-dependent transformation (see, eg, Kaleko et al., 1990; Liu et al., 1993a; Coppola et al,