Premium
Effects of 12‐0‐tetradecanoylphorbol‐13‐acetate (TPA) on rat pheochromocytoma (PC12) cells: Interactions with epidermal growth factor and nerve growth factor
Author(s) -
End David,
Tolson Nathaniel,
Yu MeiYing,
Guroff Gordon
Publication year - 1982
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041110204
Subject(s) - 12 o tetradecanoylphorbol 13 acetate , nerve growth factor , epidermal growth factor , cancer research , epidermal growth factor receptor , microbiology and biotechnology , pheochromocytoma , endocrinology , chemistry , medicine , biology , protein kinase c , phorbol ester , receptor , signal transduction
The phorbol ester tumor promoter 12‐0‐tetradecanoylphorbol‐13‐acetate (TPA) specifically inhibited the binding of radioiodinated epidermal growth factor ( 125 I‐EGF) to rat pheochromocytoma (PC12) cells in a noncompetitive fashion with an apparent K i of 11–26 nM. Both TPA and EGF elicited similar biological responses in PC12 cells including enhanced incorporation of 3 H‐choline and 32 P‐orthophosphate into macromolecules, induction of ornithine decarboxylase, and stimulation of the phosphorylation of a 30,000 MW nonhistone, chromosome‐associated protein. These effects were also elicited by nerve growth factor (NGF) which, in contrast to the former agents, is a differentiating stimulus for the PC12 cells. The effects of TPA were additive or more than additive to the effects of NGF and EGF. When PC12 cells were induced to differentiate by treatment with NGF for 72 hours, the binding of 125 I‐EGF and responses to EGF were reduced by approximately 70%. The response of PC12 cells to the tumor promoter TPA was unaffected by treatment with NGF. Thus, the qualitatively similar effects of TPA and EGF seemed to be mediated through separate receptor systems with only the EGF receptor system reduced by NGF treatment.