Although cellular proto-oncogenes are suspected of playing important roles in both normal and abnormal cell proliferation, and in the process of differentiation, the true functions of most proto-oncogenes remain hypothetical. In the proposed research, we will investigate the participation of two nuclear proto- oncogenes, c-myc and c-fos, in the transition from quiescence to renewed growth, in normal steady state growth, in abnormal proliferation in vivo, and during induced differentiation of several types of cells. We will carry out this determination by constructing recombinants that permit exogeneous manipulation, either enhancement or blockage, of the expression of these two proto-oncogenes in transfected or microinjected cells. Our preliminary studies include an example of the successful application of this strategy, demonstrating for the first time a normal cellular process for which c-fos is necessary, the transition from the quiescent state into renewed growth by fibroblasts.
