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

CESAR G. PRUCCA; FABIOLA N. VELAZQUEZ; ANDRES M CARDOZO GIZZI; BEATRIZ LEONOR CAPUTTO

Rosario

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

SAIB

Glioblastomas multiforme constitute one of the most aggressive types of brain cancer. Patients diagnosed with this class of tumors have a survival period ~1 year. The conventional treatment for these malignancies includes surgery followed by radio and chemotherapy that, as evidenced by the short survival time post-treatment, results very ineffective. Consequently, the search for novel strategies and new targets for treatment of these tumors is highly important. We have described that c-Fos, in addition to its AP-1 transcription factor is able to activate the phospholipid synthesis by an AP-1 independent mechanism. Furthermore, we found c-Fos highly expressed in all tumors of the central nervous system examined (>150) contrasting with the low or absent expression of this protein in normal tissue. 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, interferes in the interaction between c-Fos and the enzyme of phospholipid metabolism PI4KIIα thus inhibiting proliferation of human glioblastoma cells (T98G) in vitro. Truncated mutants of NA that contain the first 90 amioacids of this domain are sufficient to inhibit proliferation of T98G cells. At present we are testing the effect of injecting these peptides on tumor growth in vivo.