MODULATION OF PLASMINOGEN ACTIVATOR SYNTHESIS IN CHICK-EMBRYO FIBROBLASTS BY CYCLIC-NUCLEOTIDES AND PHOROBOL MYRISTATE ACETATE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (5) , 1579-1586
Abstract
The interaction of tumor promoters and sarcoma virus transformation with cellular regulatory mechanisms, was studied by inducing plasminogen activator synthesis by these agents in a background of changing cyclic nucleotide concentrations. Phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, apparently induces high levels of plasminogen activator production by chick embryo fibroblasts. Sarcoma virus transformation sensitizes the fibroblasts by lowering the threshold concentration for response to the action of PMA and the effects of transformation and PMA on plasminogen activator synthesis are synergistic rather than additive. The plasminogen activators produced in the PMA-, virus-induced or synergistically stimulated cultures are indistinguishable. Enzyme production in all 3 conditions is strongly, but reversibly, inhibited when cyclic nucleotide levels are raised by exposure to cyclic AMP or cholera toxin. A substantial fraction of the morphological effect that accompanies transformation is not affected by concentrations of cyclic nucleotides that suppress plasminogen activator production, and the 2 phenomena are therefore at least partially independent expressions of transformation in this system.