Impaired medulloblastoma cell survival following activation of the FOXO1 transcription factor

  • Authors:
    • Vinit Krishna Srivastava
    • Zivart Yasruel
    • Josephine Nalbantoglu
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  • Published online on: November 1, 2009     https://doi.org/10.3892/ijo_00000419
  • Pages: 1045-1051
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Abstract

Medulloblastoma is the most frequent type of childhood brain tumour. The insulin-like growth factor I receptor (IGF-IR) plays a significant neuroprotective role in medulloblastoma survival through regulation of the downstream effectors of the phosphoinositide-3-kinase-protein kinase-B (PI3K-PKB/c-Akt) pathway. One such target is Forkhead box O1 (FOXO1; FKHR), which is part of the FOXO family of Forkhead transcription factors. Phosphorylation by Akt results in cytoplasmic sequestration of FOXO1 thus inhibiting the expression of genes controlling cell death, cell proliferation, differentiation, cellular metabolism and oxidative stress. Here we show that serum starvation of medulloblastoma cells is accompanied by nuclear translocation of FOXO1. IGF-I stimulation of serum-starved cells resulted in rapid phosphorylation of Akt and FOXO1, and was associated with a significant increase in cell viability. In contrast, expression of a constitutively active form of FOXO1 that cannot be phosphorylated led to a significant reduction in medulloblastoma cell viability, even in the presence of growth factors provided by fetal bovine serum (FBS). These data suggest that the transcription factor FOXO1 may be a critical effector of medulloblastoma growth suppression.

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November 2009
Volume 35 Issue 5

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

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Spandidos Publications style
Srivastava VK, Yasruel Z and Nalbantoglu J: Impaired medulloblastoma cell survival following activation of the FOXO1 transcription factor. Int J Oncol 35: 1045-1051, 2009
APA
Srivastava, V.K., Yasruel, Z., & Nalbantoglu, J. (2009). Impaired medulloblastoma cell survival following activation of the FOXO1 transcription factor. International Journal of Oncology, 35, 1045-1051. https://doi.org/10.3892/ijo_00000419
MLA
Srivastava, V. K., Yasruel, Z., Nalbantoglu, J."Impaired medulloblastoma cell survival following activation of the FOXO1 transcription factor". International Journal of Oncology 35.5 (2009): 1045-1051.
Chicago
Srivastava, V. K., Yasruel, Z., Nalbantoglu, J."Impaired medulloblastoma cell survival following activation of the FOXO1 transcription factor". International Journal of Oncology 35, no. 5 (2009): 1045-1051. https://doi.org/10.3892/ijo_00000419