The objective of this project is to identify and characterize molecules that regulate cell proliferation in normal and neoplastic cells and to understand the mechanism of action of these molecules. This proposal is based on the hypothesis that growth factors regulate cell proliferation and that one way in which neoplastic transformation allows cells to become cancerous is to alter cellular growth factor requirements. The response of normal and malignant cells in vitro to two mitogens, platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) will be evaluated. The effects of these molecules on SV40 transformed cells and revertants of these transformed cells will be investigated. Mutants temperature sensitive in their response to mitogens will also be isolated and characterized, which should help to define the cellular processes that occur in the process of growth stimulation by mitogens. The following specific projects will be undertaken: 1. Evaluate the response of normal and malignant human epithelial cells to PDGF and EGF. 2. Determine if transformation by the oncogenic virus SV40 alters the cellular requirement for PDGF. 3. Determine if revertants of SV40 transformed cells have increased requirements for PDGF and EGF. 4. Isolate mutants of 3T3 cells temperature sensitive in their response to PDGF and EGF.