Insulin-like growth factor I regulates c-myc and GAP-43 messenger ribonucleic acid expression in SH-SY5Y human neuroblastoma cells.
In the human neuroblastoma cell line SH-SY5Y, insulin-like growth factors I (IGF-I) and II (IGF-II) are established mitogens, and IGF-I appears to promote SH-SY5Y neuronal differentiation. Studies show that c-myc gene product is a transcription factor associated with cell proliferation, and that c-myc messenger RNA levels decrease in differentiating SH-SY5Y neurons. Using Northern analysis we show that 24 h exposure of SH-SY5Y cells to IGF-I (3-10 nM) causes a 3- to 5-fold decrease in c-myc expression. The decrease in c-myc expression due to IGF-I is mediated via the type I IGF receptor and coincides with an IGF-I-mediated induction of the neuronal differentiation markers growth cone associated protein 43 and tissue type plasminogen activator. Under these conditions, IGF-I (10 nM) did not markedly affect the levels of Max messenger RNA expression. Thus, the differentiation promoting activity of IGF-I in SH-SY5Y cells in part due to IGF-I-dependent regulation of the expression of genes involved in neuronal differentiation.
Sumantran
V N
VN
Department of Neurology, University of Michigan, Ann Arbor 48109.
Feldman
E L
EL
D015152:Blotting, Northern; D002454:Cell Differentiation; D019922:GAP-43 Protein; D005786:Gene Expression Regulation; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I