C-FOS AS ACTIVATOR OF PHOSPHOLIPIDS SYNTHESIS: NEW TARGET IN BRAIN CANCER

PRUCCA CG; VELAZQUEZ FN; CARDOZO- GIZZI AM; CAPUTTO, BL

Rosario

Congreso; 50 Reunion Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2014

Glioblastomas constitute one of the most aggressive type of brain cancer. Patients who present this type of tumor have a short survival period ~1 year. The therapeutic strategy for this type of malignancy include surgery followed by radio and chemotherapy. The search for novel strategies and new targets for treatment of this tumors is highly important. Since in our lab we have described that c-Fos, an AP-1 transcription factor; is highly expressed in tumors of the central nervous system contrasting with the low or absence of its expression in normal tissue, and that we report that c-Fos is able to activate the phospholipid synthesis; we decide to exploit this properties as a new target for this tumors. The aim of this study is to test deletion mutants of c-Fos as negative dominants to block its action as activator of lipids synthesis. The overexpression of NA (aa 1-138), an deletion mutant of c-Fos, interfere in the interaction between c-Fos and one enzyme of the phospholipid metabolism (PI4KIIα) and its able to inhibits the proliferation of human glioblastoma cells (T98G) in vitro. Moreover, we tested truncated mutants of NA and we determine that the interaction with PI4KIIα involve the first 90 amioacids of this domain; and moreover, the overexpression of two peptides compassing this portion inhibit proliferation of T98G cells. We are now testing this peptides in tumors in vivo.