CYTOPLASMIC FRA-1 AND c-FOS: POTENTIAL TARGETS FOR SPECIFIC BREAST CANCER THERAPY

RACCA, AC; PRUCCA CG; CAPUTTO BL

Mar del Plata

Congreso; LI Reunion Anual del Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2015

SAIB

Breast cancer is the most common cancer in women worldwide. Most cases in less developed countries are diagnosedat late stages, so development of new therapies to eliminate established tumors is essential. Tumor cells require highrates of phospholipid (pl) synthesis to support membrane biogenesis necessary for their exacerbated growth. Fra1 andcFos activate pl synthesis to sustain proliferation and are highly expressed in breast tumors contrasting with theirundetectable levels in the normal control. c-Fos activates particular enzymes of the pl synthesis pathway at theendoplasmic reticulum by physically interacting with them. As Fra1 is highly homologous to key domains of cFos,we propose a shared mechanism for this function. Here, we demonstrate by in vitro enzymatic reactions that Fra1,like cFos, activates CDP-DAG synthase (CDS) in MDA-MB231 cells. None of them affect phosphatidylinositolsynthase activity. Similar experiments performed with deletion mutants show that CDS activation is mediated by thebasic domain of Fra-1. FRET experiments revealed that Fra-1 binds to CDS through its N-terminal domain.