N-Myc induction stimulated by insulin-like growth factor I through mitogen-activated protein kinase signaling pathway in human neuroblastoma cells

Akiko Misawa, Hajime Hosoi, Akiko Arimoto, Takuma Shikata, Shinji Akioka, Takafumi Matsumura, Peter J. Houghton, Tadashi Sawada

Producción científica: Articlerevisión exhaustiva

50 Citas (Scopus)

Resumen

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

Idioma originalEnglish (US)
Páginas (desde-hasta)64-69
Número de páginas6
PublicaciónCancer Research
Volumen60
N.º1
EstadoPublished - ene 1 2000
Publicado de forma externa

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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