Fibroblasts synthesize and secrete a number of new proteins after stimulation by peptide growth factors such as epidermal growth factor and fibroblast growth factor. This response is analogous to the secretion of lymphokines during elaboration of the immune response. We believe that as lymphokines coordinate cellular responses in cell-mediated immunity, these mitogen-induced proteins secreted by fibroblasts coordinate the growth and differentiation of solid tissues. The secreted levels of one mitogen-induced protein, which we have named """"""""mitogen-regulated protein"""""""" (MRP), appear to be regulated by growth factors at transcription. Although growth factors increased the production of MRP, we have observed that transformation decreases the production of MRP. We propose to determine whether MRP production and transformation are consistently inversely correlated. If so, it could indicate that MRP production is incompatible with transformation and that MRP might counteract the transformed state. We propose to determine what change in transformed cells results in the decreased production of MRP. We will also produce cDNA and genomic clones for MRP. With these clones we will determine the effect of growth factors and transformation on the production of MRP mRNA; the amino acid sequence of MRP; the in vivo distribution of MRP mRNA; and which geneomic sequences might be responsible for the regulation of MRP production by growth factors and by transformation. (N)
