The biological role of oncogenes--insights from platelet-derived growth factor: Rhoads Memorial Award lecture

No one in tumor biology can now be unaware of the overlap between growth factors and oncogenes. Many if not all oncogenes are now perceived as functional components of a mitogenic cascade which is normally controlled by growth factors. Some oncogenes function at the onset of this cascade by directing the synthesis of an automitogenic growth factor. Others function in the interior of the cascade by directing synthesis of a growth factor receptor or a structurally altered receptor derivative. Still other oncogenes appear to be mutated or rearranged homologues of genes the expression of which is normally induced by growth factors. Those of us working with platelet-derived growth factor (PDGF) take particular satisfaction in this new conceptual framework. It is within the molecular biology of PDGF that the overlap between growth factors and oncogenes is illustrated to its fullest and most tangible extent. An oncogene termed c-sis directs synthesis of a functional PDGF subunit. The PDGF receptor protein is in all probability encoded by a member of the src family of oncogenes. Formation of the PDGF:receptor complex stimulates expression of the c-myc and c-fos protooncogenes. My associates and I have devoted the past 10 years to the molecular biology of PDGF. Our studies on the control of the 3T3 cell cycle by PDGF contributed a pair of new jargon terms to the oncology literature--"competence" and "progression." We also had some input into the bottom end of the "oncogene hierarchy" displayed in Chart 1. The effort that we invested paid a pleasant dividend for me when, in the spring of 1984, the American Association for Cancer Research honored me with the Rhoads Memorial Award. What follows is an overview of the PDGF literature which is more anecdotal than comprehensive. My object is to show how the PDGF field moved from the level of whole animal biology, through biochemistry, down to molecular genetics in just 10 years time.