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http://dx.doi.org/10.1007/s10059-009-0142-8

Insulin-Like Growth Factor-I-Induced Androgen Receptor Activation Is Mediated by the PI3K/Akt Pathway in C2C12 Skeletal Muscle Cells  

Lee, Won Jun (Department of Exercise Science, College of Health Sciences, Ewha Womans University)
Publication Information
Molecules and Cells / v.28, no.5, 2009 , pp. 495-499 More about this Journal
Abstract
Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.
Keywords
androgen receptor; C2C12; insulin-like growth factor-I; ligand-independent mechanism; phosphatidylinositol 3-kinase;
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