Artículo
Controlling cytoplasmic c-Fos controls tumor growth in the peripheral and central nervous system
Gil, Germán A.; Silvestre, David Carlos
; Tomasini, Nicolás
; Bussolino, Daniela Fernanda
; Caputto, Beatriz Leonor
Fecha de publicación:
06/2012
Editorial:
Springer/Plenum Publishers
Revista:
Neurochemical Research
ISSN:
0364-3190
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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. © Springer Science+Business Media, LLC 2012.
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Identificadores
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Articulos(CIQUIBIC)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos(IPE)
Articulos de INST.DE PATOLOGIA EXPERIMENTAL
Articulos de INST.DE PATOLOGIA EXPERIMENTAL
Citación
Gil, Germán A.; Silvestre, David Carlos; Tomasini, Nicolás; Bussolino, Daniela Fernanda; Caputto, Beatriz Leonor; Controlling cytoplasmic c-Fos controls tumor growth in the peripheral and central nervous system; Springer/Plenum Publishers; Neurochemical Research; 37; 6; 6-2012; 1364-1371
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