Date of Award
Doctor of Philosophy
Growth regulators such as epidermal growth factor (EGF), fibroblast growth factor (FGF), 12-O-tetradecanoylphorbol 13-acetate (TPA), and type (beta) transforming growth factor (TGF-(beta)) regulate the production of certain proteins by cells in culture. EGF and TPA increased the secreted and intracellular levels of Mitogen-Regulated Protein (MRP) and Major Excreted Protein (MEP) by Swiss 3T3 cells. MRP is related by sequence to prolactin. MEP is a thiol protease located intracellularly in the lysosomes. EGF, FGF, and TPA also selectively induced a 52,000-dalton Mitogen-Induced Protein (MIP52) secreted by human fibroblasts. Two types of TGF-(beta)s were tested for their effects on the expression of secreted proteins in mouse and human fibroblasts: TGF-(beta) from human platelets and a growth inhibitor (GI/TGF-(beta)) secreted by BSC-1 cells. Both TGF-(beta)s selectively decreased the levels of MRP and MEP in mouse embryo 3T3 cells and the level of MIP52 in human skin fibroblasts. Platelet TGF-(beta) and GI/TGF-(beta) also induced one 48,000-dalton protein secreted by human fibroblasts. The major effect of GI/TGF-(beta) in regulating the level of MRP synthesis is to decrease the level of MRP mRNA in Swiss 3T3 cells. The growth state of the cells affected the ability of GI/TGF-(beta) to decrease the rate of MRP and MEP synthesis whereas this is not so for the stimulatory effects of the EGF. The stimulation of FGF, EGF, and TPA on the production of secreted MIP52 was greater in quiescent cells than in growing human fibroblasts. Synthesis of DNA and the incorporation of ('35)S methionine into total protein in both fibroblasts were not affected by platelet TGF-(beta) or GI/TGF-(beta). Thus the inhibitory effect of TGF-(beta)s on the production of these three proteins is due to a specific effect of TGF-(beta)s on the regulation of protein production that does not interfere with the ability of EGF to stimulate DNA synthesis or protein synthesis.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Chiang, Chia-Ping, "Interaction of TGF-[beta], EGF, and TPA in their effects on the production of secreted proteins by mouse 3T3 cells and human fibroblasts " (1986). Retrospective Theses and Dissertations. 8063.