Effects of tumor promoters on adenylate cyclase activity in melanoma cells in culture.

Tumor-promoting phorbol esters such as phorbol-12-myristate-13-acetate (PMA) after a short treatment (within 1 hr) stimulate [1-5] or inhibit [6--10] adenylate cyclase (AC) responses to /~-adrenoceptor agonists, depending upon the type of cells in culture. Since phorbol esters after a short treatment activate protein kinase C (PKC) [11] and the activated PKC is translocated from the cytosol to the plasma membrane [12-15], a role of PKC in the regulation of AC activity has been proposed. It has been reported that a prolonged treatment (18 hr or more) with phorbol esters causes PKC deficiency in some cells, but not in others [14, 16, 17]. The effect of a short or long treatment with phorbol esters on basal or melanocyte-stimulating hormone (MSH)-stimulated AC activity in melanoma cells has not been investigated. We now report that a short treatment of murine B-16 melanoma cells (within 1 hr) with a tumorpromoting phorbol ester, PMA, and a non-phorbol ester compound, mezerein, enhanced basal and MSH-stimulated AC activities in vitro, whereas a prolonged treatment (24 hr or more) inhibited them. These compounds also stimulated or inhibited sodium fluoride (NaF)and forskolin-stimulated AC activity, depending upon the treatment time.