Neurochemical Research

, Volume 37, Issue 6, pp 1364–1371

Controlling Cytoplasmic c-Fos Controls Tumor Growth in the Peripheral and Central Nervous System

  • Germán A. Gil
  • David C. Silvestre
  • Nicolás Tomasini
  • Daniela F. Bussolino
  • Beatriz L. Caputto
Original Paper

DOI: 10.1007/s11064-012-0763-8

Cite this article as:
Gil, G.A., Silvestre, D.C., Tomasini, N. et al. Neurochem Res (2012) 37: 1364. doi:10.1007/s11064-012-0763-8

Abstract

Some 20 years ago c-Fos was identified as a member of the AP-1 family of inducible transcription factors (Angel and Karin in Biochim Biophys Acta 1072:129–157, 1991). More recently, an additional activity was described for this protein: it associates to the endoplasmic reticulum and activates the biosynthesis of phospholipids (Bussolino et al. in FASEB J 15:556–558, 2001), (Gil et al. in Mol Biol Cell 15:1881–1894, 2004), the quantitatively most important components of cellular membranes. This latter activity of c-Fos determines the rate of membrane genesis and consequently of growth in differentiating PC12 cells (Gil et al. in Mol Biol Cell 15:1881–1894, 2004). In addition, it has been shown that c-Fos is over-expressed both in PNS and CNS tumors (Silvestre et al. in PLoS One 5(3):e9544, 2010). Herein, it is shown that c-Fos-activated phospholipid synthesis is required to support membrane genesis during the exacerbated growth characteristic of brain tumor cells. Specifically blocking c-Fos-activated phospholipid synthesis significantly reduces proliferation of tumor cells in culture. Blocking c-Fos expression also prevents tumor progression in mice intra-cranially xeno-grafted human brain tumor cells. In NPcis mice, an animal model of the human disease Neurofibromatosis Type I (Cichowski and Jacks in Cell 104:593–604, 2001), animals spontaneously develop tumors of the PNS and the CNS, provided they express c-Fos (Silvestre et al. in PLoS One 5(3):e9544, 2010). Treatment of PNS tumors with an antisense oligonucleotide that specifically blocks c-Fos expression also blocks tumor growth in vivo. These results disclose cytoplasmic c-Fos as a new target for effectively controlling brain tumor growth.

Keywords

Cytoplasmic c-FosBrain tumorsMembrane biogenesisPhospholipid synthesisRegulation

Supplementary material

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Supplementary material 1 (TIFF 1787 kb)
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Supplementary material 2 (TIFF 1789 kb)
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Supplementary material 3 (TIFF 1794 kb)

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Germán A. Gil
    • 1
  • David C. Silvestre
    • 1
    • 2
  • Nicolás Tomasini
    • 1
    • 3
  • Daniela F. Bussolino
    • 1
    • 4
  • Beatriz L. Caputto
    • 1
  1. 1.Departamento de Química Biológica, CIQUIBIC, Facultad de Ciencias QuímicasUniversidad Nacional de CórdobaCórdobaArgentina
  2. 2.Institut Curie, Telomeres & Cancer Team - CNRS UMR 3244/UPMC, Bât. Trouillet-RossignolParisFrance
  3. 3.Instituto de Patología Experimental, Facultad de Ciencias de la SaludUniversidad Nacional de SaltaSaltaArgentina
  4. 4.Departamento de Farmacología, Facultad de Ciencias QuímicasUniversidad Nacional de CórdobaCórdobaArgentina