N-Myc Induction Stimulated by Insulin-like Growth Factor I through Mitogen-activated Protein Kinase Signaling Pathway in Human Neuroblastoma Cells

摘要: Insulin-like growth factor I (IGF-I) stimulates proliferation, survival, and differentiation in many cell types, including pediatric neuroblastomas. The effect is mediated via the type IGF-I receptor (IGF-IR), which essential for these cells. Several lines of evidence indicate that IGF-IR function may be particularly important pathogenesis neuroblastoma. Amplification N- myc oncogene or overexpression N-Myc oncoprotein has been reported to associated with resistance therapy poor prognosis It was therefore interest analyze whether signaling regulated expression KP-N-RT human neuroblastoma cells as an experimental model amplified . We found induces mRNA protein maximums four six times more than basal level at 2 3 h after stimulation, respectively. These effects were blocked by a neutralizing antibody against (α-IR3). Exogenous induced phosphorylation activation extracellular signal-regulated kinases p44/42 (ERK1 ERK2), maximal 30 min stimulation. MEK1 inhibitor PD98059 reduced IGF-I-mediated MAPKs produced parallel reduction IGF-I-stimulated induction. Furthermore, both α-IR3 inhibited G1-S cycle progression stimulated IGF-I. Our results demonstrate line RNA establishes clear correlation between induction MAPK signaling.