The loss of EBP50 expression potentiates cell transformation

KREIMANN E , MORALES F, TAKASHAHI Y, MOLINA J, GEORGESCU M

Mendoza, Argentina

Congreso; XXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2008

Sociedad de Biología de Cuyo

NHERF1/EBP50 is an adaptor protein containing two PDZ domains and an Ezrin-binding region that interacts with proteins at the plasma membrane and regulates its interaction with the cell cytoskeleton, endocytic and signaling pathways.  It was described that EBP50 interacts with the carboxy domain of Beta-Catenin through it PDZ2 domain and it promotes transcriptional transactivation in liver cancer. However, the effect of the EBP50-Beta-catenin interaction in the formation and maintenance of the adherent junctions had not been studied. Furthermore, the role of EBP50 in cell transformation is still unclear. We have generated the EBP50 deficient mice in order to define the importance of EBP50 protein in cell growth, cell transformation and assembly and stability of the adherent junctions.  Mouse embryonic fibroblasts (MEFs) from the EBP50 (-/-) and NHERF1 (+/+) littermates were isolated from E14 embryos.  No difference in proliferation between NHERF1 (-/-) and (+/+) was apparent, however, the NHERF1 (-/-) MEFs were capable of forming colonies in soft agar.  There was an increase in the cytoplasmic accumulation of Beta-Catenin and a disruption of the interaction with its partner proteins. These findings showed that the lack of the NHERF1 function potentiates cell transformation and NHERF1 gene could act as a tumor suppressor gene.