The epidermal growth factor-induced cell migration and expression of the 47,000 Mr secreted glycoprotein EIP-1 of rat liver epithelial cells are down-modulated by cyclic AMP.

The migration of rat liver epithelial cells induced by epidermal growth factor (EGF) was inhibited by cyclic AMP (cAMP) and cholera toxin, but not by cGMP, cAMP and cholera toxin also inhibited the expression of the EGF/transforming growth factor (TGF) alpha-inducible protein EIP-1 (Mr 47,000), but not that of other proteins induced by the growth factor. cAMP therefore specifically and selectively represses the EGF-induced expression of this protein, which by synthesis in the presence of tunicamycin and by enzymatic treatments was shown to be N-glycosylated and sialylated. The close correlation of the expression of EIP-1 with the growth factor-induced migration suggests that this glycoprotein is involved in the cellular translocation process. Modulation of cell migration and of EIP-1 expression through increased intracellular concentrations of cAMP indicate that factors operating through this signal system can modulate the phenotypic and gene expression changes mediated by the EGF-receptor. Identification of the ligand(s) that can cause the cAMP-mediated effects might be an important step towards understanding the regulation of liver cell migration in vivo.