N-terminal domain of c-Fos as a negative dominant for brain cancer therapy.

PRUCCA CG; VELAZQUEZ FN; RACCA, AC; CAPUTTO BL

Cordoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

lioblastoma multiforme, a WHO class IV tumor, is the most aggressive central nervous system (CNS) cancer. After diagnosis, the average survival period for these patients is ~1 year with no significant improvements in this survival period observed in the last decades. The development of new therapeutic strategies and the identification of new targets is the principal aim of the field. We have reported a new activity for c-Fos. In addition to its AP1 transcription function it activates phospholipid synthesis in the cytoplasm associated to the endoplasmic reticulum. Since c-Fos is markedly overexpressed in tumors contrasting with lack of detectable expression observed in normal CNS, we propose this cytoplasmic activity of c-Fos as new target for glioblastoma treatment. The aim of 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 of T98G cells (a glioblastoma multiforme cell line) by interfering with the physical association of c-Fos to phosphatidylinositol 4 kinase II α. At present we are testing these negative dominant in an in vivo model of CNS tumors