c-FOS CONTROLS CNS AND PNS TUMOR GROWTH

NICOLÁS TOMASINI; DAVID C. SILVESTRE; BEATRIZ L. CAPUTTO

Mar del Plata

Otro; 43rd Annual Meeting of Argentine Society for Biochemistry and Molecular Biology; 2007

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Neurofibromatosis Type I (NF1) is a syndrome affecting 1:3500 individuals and is characterized by the development of tumors in the peripheral (PNS) and the central (CNS) nervous systems. Many patients were progress to generate glioblastoma, the most malignant type of brain tumors. The NPcis mice is an animal model of NF1; these mice develop CNS gliomas and PNS tumors (neurofibromas). Previously we found that c-Fos, in addition to its AP-1 transcription factor activity, associates to the endoplasmic reticulum (ER) and activates the synthesis of phospholipids for the genesis of membrane required for cell proliferation and growth of many human brain tumors. Herein, the c-Fos dependent activation was examined in brain tumors and in neurofibromas from NPcis mice. High levels of c-Fos co-localizing with ER markers were found both in brain tumors and in neurofibromas. These levels correlate with high rates of cell proliferation. Blocking c-Fos expression in brain of NPcis mice decreased phospholipid synthesis and proliferation levels to those of non-treated animals, whereas this treatment in peripheral tumors significantly lowered tumor burden. Similar results were observed in 10 stable cell lines from neurofibromas and in another 10 from brain tumor cells. It is hypothesized that controlling c-Fos expression will enable the control of tumor growth in tumors of the PNS and the CNS.