Abstract
Mouse NIH 3T3 cells expressing the human c-fms protooncogene encoding the receptor for colony-stimulating factor 1 (CSF-1) are able to proliferate in serum-free medium containing platelet-derived growth factor (PDGF), insulin, transferrin, and albumin as the only exogenous proteins. When PDGF and insulin were replaced by purified human recombinant CSF-1, the cells became spindle shaped and refractile, were no longer contact inhibited, and proliferated to high densities. Thus, transduction of the human c-fms gene into mouse fibroblasts can not only reprogram their growth factor requirements but can also induce ligand-dependent features of cell transformation. NIH 3T3 cells stably transformed by the feline v-fms oncogene or by a mutated, oncogenic human c-fms gene were able to proliferate in the absence of exogenous growth factors. A monoclonal antibody that prevents signal transduction by the human CSF-1 receptor inhibited the growth of cells transformed by the activated c-fms oncogene, confirming that CSF-1 receptor function was required to abrogate growth factor requirements and to maintain the transformed state.