Intracellular calcium and skin tumor promotion: Calcium regulation of the induction of epidermal ornithine decarboxylase activity by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate

The role of calcium in epidermal ornithine decarboxylase (ODC) induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) was determined in adult mouse skin explants maintained in a serum-free Eagle's HeLa cell medium. Chelation of extracellular calcium by ethyleneglycol-bis-(β-aminoethyl ether) N,N′-tetraacetic acid (EGTA) prevented ODC induction by TPA, which could be resumed upon calcium restoration in the medium. Extracellular magnesium could not replace calcium for ODC induction by TPA. Concurrent incubation of skin pieces with a calmodulin inhibitor trifluoperzine (TFP) inhibited ODC induction. Furthermore, inclusion in the medium of lanthanum, which has a higher affinity for calcium-binding sites than calcium and displaces surface-bound calcium, inhibited ODC induction by TPA.