“…For many fibroblast and established tumor cell lines, this second messenger is either without effect or is a negative regulator of proliferation (Pastan et al, 1975). In contrast, skin and mammary epithelia (Green, 1978;Yang et al, 1980), hepatocytes (Friedman et al, 1981), thyrocytes (Roger et al, 1983), Schwann cells (Raff et al, 1978a) and melanocytes (Mayer, 1982), among many other cell types, respond to elevation of intracellular cAMP by dividing. For these cells, combined application of cAMP and a polypeptide mitogen, such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) or insulin, typically promotes a synergistic (greater than additive) stimulation of cell proliferation (Raff et al, 1978a;McGowan et al, 1981;Roger and Dumont, 1984;Westermark et al, 1986;Roger et al, 1987).…”