Basic FGF and IGF-I promote differentiation of human SH-SY5Y neuroblastoma cells in culture.
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.
Lavenius
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Department of Pathology, University of Uppsala, University Hospital, Sweden.
Parrow
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Nånberg
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Påhlman
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D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D019922:GAP-43 Protein; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009447:Neuroblastoma; D009479:Neuropeptides / Q000096:biosynthesis; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D019922:GAP-43 Protein; D006133:Growth Substances; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate