Insulin-like growth factor I shifts from promoting cell division to potentiating maturation during neuronal differentiation.
SH-SY5Y neuroblastoma cells undergo neuronal differentiation and their proliferation is inhibited when they are treated with phorbol 12-myristate 13-acetate (PMA). Insulin and insulin-like growth factor I (IGF-I) are mitogens for the nontreated SH-SY5Y cells, whereas the proliferative response to such factor stimulation is lost upon differentiation, in spite of the fact that the receptors for insulin and IGF-I remain expressed and functional in the differentiated cells. Here we show that the PMA-induced differentiation of SH-SY5Y cells grown in a serum-free medium is strongly potentiated by nanomolar concentrations of IGF-I, as judged by morphology and markers for neuronal differentiation--e.g., neuropeptide tyrosine and growth-associated protein 43. Also, insulin and IGF-II potentiated the phorbol ester-induced differentiation, although less efficiently than IGF-I. Using blocking anti-receptor antibodies, it could be shown that the differentiation induced by these factors, in combination with PMA, was primarily mediated through the IGF-I receptor.
Påhlman
S
S
Department of Pathology, University of Uppsala, University Hospital, Sweden.
Meyerson
G
G
Lindgren
E
E
Schalling
M
M
Johansson
I
I
D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007700:Kinetics; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009478:Neuropeptide Y / Q000032:analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D009478:Neuropeptide Y; D012334:RNA, Neoplasm; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013755:Tetradecanoylphorbol Acetate