Possible involvement of a lanthanide-sensitive protein kinase C substrate in lanthanide promotion of neoplastic transformation

The rare earth elements lanthanum and terbium (0.1— 1.0 mM), pharmacological analogs of calcium, induced neo-plastic transformation of 12-0-tetradecanoylphorbol-13-acetate (TPA)-sensitive (P+) and to a lesser extent TPA-resistant (P—) preneoplastic mouse JB6 epidermal cells. A maximum of 2500 anchorage-independent colonies per 104 cells were induced in P+ lines, a response comparable to that induced by phorbol esters (1.6-16 nM). The maximum lan-thanide-induced colony yield in P- lines was 20 % of that in P+ lines ( ~ 550 colonies), and was observed under conditions where TPA induced < 30 colonies per 10 * cells. Lanthanides and TPA produced a synergistic effect on colony size in P+ cells. Lanthanides are not promoting transformation merely by mimicking high calcium: adding exogenous extracellular calcium (up to 50.0 mM) or using calcium ionophore (up t