The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on phospholipid metabolism of human epidermal keratinocytes in culture

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated the release of [3H]choline from prelabelled membrane phospholipids of cultured keratinocytes obtained from normal human skin. In contrast, TPA in the concentration range of 10(-12) to 10(-6) g/ml failed to induce deacylation of [3H]arachidonic acid or stimulate [3H]prostaglandin production in prelabelled keratinocytes. In addition, TPA did not induce [3H]choline incorporation into the membrane phospholipids of these cells. The previously reported inability of TPA to stimulate a proliferative response in these cell cultures may be related to the resistance of these cells to TPA-induced alterations of arachidonate metabolism.