The induction of ornithine decarboxylase by nerve growth factor and epidermal growth factor in PC12 cells

Both nerve growth factor and epidermal growth factor cause an induction of ornithine decarboxylase in the rat pheochromocytoma clone PC12. The induction by nerve growth factor is transcription-dependent and occurs within 4 to 6 h. Antibody studies indicate that nerve growth factor must be present for 2-3 h to obtain full induction. Nerve growth factor is synergistic with either N6, O2-dibutyryl cyclic 3',5'-adenosine monophosphate (dBcAMP) or 3-isobutyl-1-methylxanthine (IBMX) in the induction. The magnitude of ornithine decarboxylase induction is influenced by the density of the culture. Synchronized cell populations show the greatest sensitivity to nerve growth factor just before, or immediately upon, entering S phase. The induction of ornithine decarboxylase by epidermal growth factor appears to be quite similar to that exhibited by nerve growth factor. Epidermal growth factor is active in the range of ng/ml. The time course of the induction is the same, as is the need for the peptide to remain in contact with the cells for several hours. Putrescine inhibits the induction and dBcAMP and IMBX accentuate it. Cells appear to be sensitive to epidermal growth factor also near the G1/S border. In spite of the marked similarities in these inductions, a maximal level of nerve growth factor plus a maximal level of epidermal growth factor yields greater induction than either alone, indicating the inductions occur by somewhat different mechanisms.