Melanoma cells which require cyclic AMP for growth

THE cyclic forms of AMP, GMP and CMP have been implicated as agents which either stimulate or inhibit cell division. Pastan et al. reviewed this topic1and others have dealt with it2–6. Our studies of the growth of cultured melanoma cells have focused on the inhibitory effects of cyclic AMP7. We analysed variant cells that can grow in the presence of agents, such as melanocyte stimulating hormone (MSH), which increase the intracellular levels of cyclic AMP and inhibit the growth of wild-type cells. We describe here a class of variants which are not only resistant to the inhibition, but require cyclic AMP to grow at the rate normally observed in wild-type cells. In one such variant, division was markedly stimulated when either MSH, theophylline, isobutyl methyl xanthine, cholera toxin, prostaglandin E1(PGE1) or dibutyryl cyclic AMP was added to the medium. Each agent inhibited the growth of wild-type cells. The cells were temperature-sensitive in that they expressed the variant phenotype at 37 °C, but behaved as the wild type at 40 °C. Studies of dose responses to dibutyryl cyclic AMP revealed that growth was also enhanced in the wild type by lower concentrations of the nucleotide (10−5M), a fact that had gone unnoticed in melanoma cells but has been reported for other cell types1. These findings suggest a stimulatory as well as inhibitory role for cyclic AMP in control of growth of melanoma cells.