Tumor-promoting phorbol diester mimics two distinct neuronotrophic factors

Abstract

The two purified neuronotrophic factor proteins, nerve growth factor (NGF) and ciliary neuronotrophic factor (CNTF), differ in molecular properties and in their action on certain neuronal cell types. The survival in culture of dissociated chick embryonic day 8 dorsal root ganglionic neurons is supported by NGF and day 8 ciliary ganglionic neurons by CNTF, but neither factor can be a substitute for the other. Here we report that a known tumor-promoting phorbol diester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), can support the survival of both neuronal types in the absence of either NGF or CNTF and does so with the same efficacy as the corresponding trophic factor. The inactive phorbol derivative, 4-alpha-phorbol-didecanoate, does not support either neuronal type. The combined provision of suboptimal doses of TPA and NGF or CNTF does not reveal synergistic effects. These results suggest that TPA, NGF and CNTF may exert their neuronal survival promoting influences through a common molecular mechanism.