CONTROLLING CYTOPLASMIC C-FOS CONTROLS TUMOR GROWTH IN THE PERIPHERAL AND CENTRAL NERVOUS SYSTEM

16. GERMÁN A.GIL, DAVID C. SILVESTRE1, DANIELA F. BUSSOLINO2 & BEATRIZ L. CAPUTTO

SPRINGER/PLENUM PUBLISHERS

Año: 2012 p. 1120 - 1120

ome 20 years ago c-Fos was identified as a member of the AP-1 family of inducible transcription factors (1). More recently, an additional activity was described for this protein: it associates to the endoplasmic reticulum and activates the biosynthesis of phospholipids (2,3), the quantitatively most important component of cellular membranes. This latter activity of c-Fos determines the rate of membrane genesis and consequently of growth in differentiating PC12 cells (3). In addition, it has been shown that c-Fos is over-expressed both in PNS and CNS tumors (4). 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, a