The Epidermal Growth Factor/cAMP-Inducible EctoCa2+-ATPase of Human Hepatoma Li-7A Cells Is Similar to Rat Liver EctoATPase/Hepatocyte Cell Adhesion Molecule (Cell-CAM 105)

Human hepatoma Li-7A cells exhibit two cell surface ATPase (ectoATPase) activities distinguishable by their different biochemical properties. The activity of the minor ectoATPase, ectoCa2+-ATPase, is enhanced severalfold when Li-7A cells are treated simultaneously by epidermal growth factor (EGF) and cAMP elevating agents (Knowles, A. F., 1990, Arch. Biochem. Biophys. 283, 114-119). Here we report that the human ectoCa2+-ATPase is biochemically similar to the major rat hepatocyte ectoATPase/cell adhesion molecule (cell-CAM 105) with respect to response to divalent ions and sulfhydryl reagents. Furthermore, the binding of rat liver ectoATPase antibody increased markedly in EGF/cholera toxin/hydrocortisone-treated Li-7A cells compared to untreated cells. Western blot analysis revealed cross-reactivity of the antibody with a 125-kDa protein. Partial purification of ectoCa2+ATPase from EGF/cholera toxin/hydrocortisone-treated Li-7A cells confirmed that enrichment of the 125-kDa protein correlated with an increase in ATPase activity. We conclude that EGF and increased levels of cAMP lead to increased synthesis of the ectoCa2+-ATPase in Li-7A cells. The present demonstration of similarity between the ectoCa2+-ATPase and a rat liver cell adhesion molecule, cell-CAM 105, contributes significantly to an understanding of the implication of down-regulation of ectoCa2+-ATPase during hepatocyte-hepatoma transformation.