Abstract B46: Investigating the role of β-arrestin-2 in prostate cancer disparity using a β-arrestin-2 deficient mouse model of prostate cancer

Abstract

Abstract African American men are more likely to develop and die from prostate cancer than Caucasian American men. While a complex interaction of social, environmental, and biological factors is likely to blame, molecular mechanisms of prostate cancer disparity remain poorly understood. Elucidation of these mechanisms is critical if we are to achieve better treatment options and ultimately, patient survival for African American men. β-arrestin-2 was initially recognized for its role in G-protein coupled receptor desensitization. More recent studies have demonstrated that several pathways critical to prostate cancer progression converge at β-arrestin-2 including androgen metabolism, angiogenesis, and metastasis. Preliminary data in our lab shows that prostate cell lines derived from Caucasian American men express less -arrestin-2 than those from African American men. This study aims to test the hypothesis that loss of β-arrestin-2 expression in prostate tumors attenuates tumor progression. In order to study this, we have established a β-arrestin-2 deficient TRAMP mouse model. TRAMP+/β-arrestin-2 KO mice develop tumors that are smaller than those in TRAMP+/β-arrestin-2 WT mice at 6 months of age. Similar results were observed when orthotopic TRAMP-C1 tumors were established in C57BL/6 mice. β-arrestin-2 knockdown in these cells resulted in delayed tumor growth. Taken together these data support the idea that increased β-arrestin-2 expression correlates with enhanced tumor progression providing a possible biological mechanism of prostate cancer disparity. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B46.