Role of hypercholesterolemia in modifying the composition of lipid rafts microdomains in prostate cancer

Abstract

Lipid rafts are functional microdomains enriched in cholesterol and sphingolipids which are present in biological membranes. Operationally rafts are defined as detergent-resistant membranes (DRMs) since they resist to extraction by certain cold detergents. In the last decade, rafts have been described as potentially important organizers of survival signaling in prostate cancer cells, with cholesterol playing a crucial role. Since the risk of aggressive prostate cancer is believed to be linked to the consumption of a 'western diet' enriched in fatty, high cholesterol foods, one possible mechanism through which cholesterol may promote prostate cancer progression is through modifying lipid raft microdomains resulting in proteinaceous changes in raft composition. In this study we will investigate the effect of hypercholesterolemia upon the protein composition of rafts from prostate cancer xenografts. The proteomic changes induced by high levels of cholesterol in rafts will provide new insights into cholesterol's role in promoting prostate cancer. We also anticipate the possibility of identifying new prostate cancer-associated biomarkers. (AU)