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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)64-69
Number of pages6
JournalCancer Research
Volume60
Issue number1
StatePublished - Jan 1 2000
Externally publishedYes

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Mitogen-Activated Protein Kinases
Neuroblastoma
Insulin-Like Growth Factor I
IGF Type 1 Receptor
Mitogen-Activated Protein Kinase 3
Phosphorylation
myc Genes
Oncogene Proteins
Extracellular Signal-Regulated MAP Kinases
Neutralizing Antibodies
Cell Cycle
Theoretical Models
RNA
Pediatrics
Cell Line
Messenger RNA
Survival
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Misawa, A., Hosoi, H., Arimoto, A., Shikata, T., Akioka, S., Matsumura, T., ... Sawada, T. (2000). N-Myc induction stimulated by insulin-like growth factor I through mitogen-activated protein kinase signaling pathway in human neuroblastoma cells. Cancer Research, 60(1), 64-69.

N-Myc induction stimulated by insulin-like growth factor I through mitogen-activated protein kinase signaling pathway in human neuroblastoma cells. / Misawa, Akiko; Hosoi, Hajime; Arimoto, Akiko; Shikata, Takuma; Akioka, Shinji; Matsumura, Takafumi; Houghton, Peter J; Sawada, Tadashi.

In: Cancer Research, Vol. 60, No. 1, 01.01.2000, p. 64-69.

Research output: Contribution to journalArticle

Misawa, A, Hosoi, H, Arimoto, A, Shikata, T, Akioka, S, Matsumura, T, Houghton, PJ & Sawada, T 2000, 'N-Myc induction stimulated by insulin-like growth factor I through mitogen-activated protein kinase signaling pathway in human neuroblastoma cells', Cancer Research, vol. 60, no. 1, pp. 64-69.
Misawa, Akiko ; Hosoi, Hajime ; Arimoto, Akiko ; Shikata, Takuma ; Akioka, Shinji ; Matsumura, Takafumi ; Houghton, Peter J ; Sawada, Tadashi. / N-Myc induction stimulated by insulin-like growth factor I through mitogen-activated protein kinase signaling pathway in human neuroblastoma cells. In: Cancer Research. 2000 ; Vol. 60, No. 1. pp. 64-69.
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