Abstract 5299: Evaluation of apolipoprotein E polymorphism on the aggressive potential of prostate cancer cell lines.

Abstract

Abstract Introduction: Defective cholesterol-modulating apolipoprotein E (ApoE) isoforms could exacerbate prostatic neoplasia. Recent evidence strongly suggests that specific genetic variants of ApoE control peripheral tissue cholesterol efflux. Defects in ApoE may result in reduced prostate cancer cell cholesterol efflux and enriched concentrations of cholesterol in membranes by reducing clearance. Membrane-rich cholesterol could potentially activate cancer-driven signaling processes. Objective: To determine the relevance of specific ApoE phenotypes as risk factors of aggressive prostate cancer based on their influence on reverse cholesterol transport. Methods: We evaluated ApoE genotypes of the weakly tumorigenic or nonaggressive prostate cancer cell lines (LNCaP and MDA PCA 2b), and the moderate and highly tumorigenic or aggressive prostate cancer cell lines (PC-3 and DU-145). We examined whether ApoE2/E4 variants were associated with tumor aggressiveness via the expression of caveolin-1(cav-1), a cholesterol-regulated pro-carcinogenic gene. Results: We observed that the nonaggressive prostate cancer cell lines carried either the Apo ε3/ε3 or ε3/ε4 alleles, while the aggressive prostate cancer cell lines carried the Apo ε2/ε4 alleles. Our results showed a two-fold increase in the expression of cav-1 in the aggressive cell lines, as opposed to the nonaggressive ones. There was a significantly (p<0.01) greater cholesterol efflux from the nonaggressive cells lines compared to the aggressive cells. Also, the aggressive cell lines retained and localized more cholesterol in their membranes as opposed to the less aggressive cell lines. Conclusions: These results suggest an association between cholesterol status and the aggressive potential of prostate cancer cells. It also highlights the need for further investigation into whether ApoE2/E4 is the dysfunctional phenotype, and whether it has the potential as a biomarker of aggressive prostate cancer. GRANT SUPPORT: NIH R25CA047888 Citation Format: Godwin O. Ifere, Wendy Demark-Wahnefried, Renee Desmond, Tim R. Nagy. Evaluation of apolipoprotein E polymorphism on the aggressive potential of prostate cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5299. doi:10.1158/1538-7445.AM2013-5299