Insulin-like growth factor-I has different effects on myogenin induction and cell cycle progression in human alveolar and embryonal rhabdomyosarcoma cells

  • Authors:
    • Kunihiko Tsuchiya
    • Hajime Hosoi
    • Akiko Misawa-Furihata
    • Peter J. Houghton
    • Tohru Sugimoto
  • View Affiliations

  • Published online on: July 1, 2007     https://doi.org/10.3892/ijo.31.1.41
  • Pages: 41-47
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Abstract

Alveolar rhabdomyosarcoma (RMS) has a much poorer outcome than embryonal RMS. In this study, we found that IGF-I affected the induction of myogenin and cell cycle progression in alveolar RMS cells, but not in embryonal RMS cells. IGF-I enhanced the induction of myogenin protein in alveolar RMS SJ-Rh30 and KP-RMS-MS cells as it did in myoblast C2C12 cells, but not in embryonal RMS RD or KP-RMS-KH cells. IGF-I induction of myogenin protein was blocked by anti-IGF-IR monoclonal antibody αIR-3 and the mTOR-specific inhibitor rapamycin. In Rh30mTOR-rr cells, which stably express a rapamycin-resistant mutant mTOR, rapamycin did not inhibit IGF-I induction of myogenin protein. These data suggest that IGF-I induces myogenin in alveolar RMS cells through the IGF-IR/mTOR pathway. In C2C12 cells, IGF-I induces myogenin protein followed by cell cycle arrest leading to myogenic differentiation. IGF-I promoted G1-S cell cycle progression without any signs of terminal differentiation in alveolar RMS cells. On the other hand, IGF-I promoted neither cell cycle arrest nor G1-S cell cycle progression in embryonal RMS cells. In alveolar RMS SJ-Rh30 cells, 4E-BP1, one of two effectors downstream of mTOR, was continuously hyperphosphorylated by IGF-I, whereas in embryonal RMS RD cells, 4E-BP1 was only transiently hyperphosphorylated. These findings suggest that the different effects of IGF-I on myogenin induction and cell cycle progression in alveolar and embryonal RMS cells are due to a difference of phosphorylation status of 4E-BP1. These different responses to IGF-I help to explain immunohistochemical and clinical behavioral differences between alveolar and embryonal RMS.

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July 2007
Volume 31 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Tsuchiya K, Hosoi H, Misawa-Furihata A, Houghton PJ and Sugimoto T: Insulin-like growth factor-I has different effects on myogenin induction and cell cycle progression in human alveolar and embryonal rhabdomyosarcoma cells. Int J Oncol 31: 41-47, 2007
APA
Tsuchiya, K., Hosoi, H., Misawa-Furihata, A., Houghton, P.J., & Sugimoto, T. (2007). Insulin-like growth factor-I has different effects on myogenin induction and cell cycle progression in human alveolar and embryonal rhabdomyosarcoma cells. International Journal of Oncology, 31, 41-47. https://doi.org/10.3892/ijo.31.1.41
MLA
Tsuchiya, K., Hosoi, H., Misawa-Furihata, A., Houghton, P. J., Sugimoto, T."Insulin-like growth factor-I has different effects on myogenin induction and cell cycle progression in human alveolar and embryonal rhabdomyosarcoma cells". International Journal of Oncology 31.1 (2007): 41-47.
Chicago
Tsuchiya, K., Hosoi, H., Misawa-Furihata, A., Houghton, P. J., Sugimoto, T."Insulin-like growth factor-I has different effects on myogenin induction and cell cycle progression in human alveolar and embryonal rhabdomyosarcoma cells". International Journal of Oncology 31, no. 1 (2007): 41-47. https://doi.org/10.3892/ijo.31.1.41