info:eu-repo/semantics/article
Controlling cytoplasmic c-Fos controls tumor growth in the peripheral and central nervous system
Fecha
2012-06Registro en:
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
0364-3190
CONICET Digital
CONICET
Autor
Gil, Germán A.
Silvestre, David Carlos
Tomasini, Nicolás
Bussolino, Daniela Fernanda
Caputto, Beatriz Leonor
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.