Molecular and functional characterization of the human RNASET2 oncosuppressor gene.

Abstract

The RNASET2 gene maps to human chromosome 6q27, a region that has been consistently found rearranged in many solid and hematological tumors. This gene encodes for the only human secreted acid ribonuclease of the T2 family. Our research group’s studies have demonstrated a remarkable RNASET2-mediated tumor suppressive activity. Indeed, we recently reported that the oncosuppressive activity of RNASET2 in vivo involves the recruitment toward the tumor mass of cancer-suppressive innate immune cells belonging to the monocyte/macrophage lineage, particularly M1 macrophages, which are known to carry out a cancer antagonizing role. Given these premises, the aim of my PhD thesis work was to further characterize this gene from a functional point of view. Firstly, we analyzed the effect of RNASET2 protein in the recruitment and polarization pattern of macrophages in in vitro systems. Furthermore, since all previous in vivo experiments were performed using nude mice, we started developing a syngeneic mouse model in order to study the role of this gene in an immunocompetent model. Finally, we recently demonstrated that RNASET2 also behaves as a stress response gene and strongly affects the actin cytoskeleton. To shed more lights on its pleiotropic functions, we also started to investigate the role of this gene in the context of mammary tumorigenesis and morphogenesis