Abstract
Phorbolester-triggered differentiation of SH-SY5Y neuroblastoma cells requires serum and a prolonged activation of protein kinase C (PKC). Under serum-free conditions development of a mature phenotype requires phorbolester in combination with a member of either the insulin-like growth factor (IGF) or the platelet-derived growth factor family. Here we report that basic and acidic fibroblast growth factor (FGF) and epidermal growth factor, but not nerve growth factor, synergistically potentiate phorbolester-induced differentiation. Alone these factors induced a mitogenic response which varied in magnitude, with basic FGF and IGF-I being the two most potent mitogens. However, a combination of basic FGF and IGF-I induced differentiation as judged by morphology and the increase in growth associated protein (GAP-43) and neuropeptide tyrosine mRNA levels. In contrast to the phenotype obtained in the presence of phorbolester, bFGF and IGF-I-treated SH-SY5Y cells retained their capacity to proliferate. Finally, in these cells, the phosphorylation of the endogenous PKC substrate, myristoylated alanine-rich C-kinase substrate (MARCKS), was slightly increased during several days, suggesting an involvement of PKC in the bFGF and IGF-I-induced differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Northern
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Cell Differentiation / drug effects*
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Cell Division / drug effects
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Cell Line
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Fibroblast Growth Factor 1 / pharmacology
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Fibroblast Growth Factor 2 / pharmacology*
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GAP-43 Protein
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Growth Substances / biosynthesis
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Humans
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Insulin / pharmacology
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Insulin-Like Growth Factor I / pharmacology*
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Insulin-Like Growth Factor II / pharmacology
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Intracellular Signaling Peptides and Proteins*
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Membrane Glycoproteins / biosynthesis
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Membrane Proteins*
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Myristoylated Alanine-Rich C Kinase Substrate
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Nerve Growth Factors / pharmacology
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Nerve Tissue Proteins / biosynthesis
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Neuroblastoma
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Neuropeptides / biosynthesis
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Phosphorylation
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Platelet-Derived Growth Factor / pharmacology
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Protein Kinase C / metabolism
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Proteins / metabolism
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Recombinant Proteins / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Cells, Cultured
Substances
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GAP-43 Protein
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Growth Substances
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Insulin
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Intracellular Signaling Peptides and Proteins
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MARCKS protein, human
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Membrane Glycoproteins
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Membrane Proteins
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Nerve Growth Factors
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Nerve Tissue Proteins
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Neuropeptides
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Platelet-Derived Growth Factor
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Proteins
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RNA, Messenger
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Recombinant Proteins
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Fibroblast Growth Factor 2
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Fibroblast Growth Factor 1
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Myristoylated Alanine-Rich C Kinase Substrate
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Insulin-Like Growth Factor I
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Insulin-Like Growth Factor II
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Protein Kinase C
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Tetradecanoylphorbol Acetate