N-TERMINAL DOMAIN OF C-FOS AS A NEGATIVE DOMINANT FOR BRAIN CANCER THERAPY

PRUCCA, CÉSAR G.; VELAZQUEZ, FABIOLA; RACCA, ANA C.; CAPUTTO, BEATRIZ L.

Córdoba

Congreso; LII SAIB; 2016

SAIB

Glioblastoma multiforme, a WHO class IV tumor, is the most aggressive central nervous system (CNS) cancer. After diagnosis, theaverage survival period for these patients is ~1 year with no significant improvements in this survival period observed in the lastdecades. The development of new therapeutic strategies and the identification of new targets is the principal aim of the field. We havereported a new activity for c-Fos. In addition to its AP1 transcription function it activates phospholipid synthesis in the cytoplasmassociated to the endoplasmic reticulum. Since c-Fos is markedly overexpressed in tumors contrasting with lack of detectableexpression observed in normal CNS, we propose this cytoplasmic activity of c-Fos as new target for glioblastoma treatment. The aimof the present work is to test N-terminal deletion mutants of c-Fos as possible negative dominants of the lipid activation capacity of c-Fos. Through transfection and profection methods we identified negative dominants whose overexpression inhibits proliferation ofT98G cells (a glioblastoma multiforme cell line) by interfering with the physical association of c-Fos to phosphatidylinositol 4 kinaseII α. At present we are testing these negative dominant in an in vivo model of CNS tumors