Discipline: Biological Sciences
Subcategory: Cancer Research
Timera Brown - Tougaloo College
Co-Author(s): Xinchun Zhou, University of Mississippi Medical Center, MS Jinghe Mao, Lianni Li, Josh Agee, and Alex Thompson, Tougaloo College, MS
Prostate cancer is the most diagnosed cancer, and the second leading cause of cancer death in men. When treating patients with prostate cancer, no ideal biomarkers for the differentiation of indolent and malignant cases at time of diagnosis, and no effective therapy for castration resistant prostate cancer are two most prominent challenges among others. Thus, discovering specific predictive biomarkers and new therapeutic interventions for prostate cancer will be of great significance. Cholesteryl esters (CEs) are mainly considered as a storage form of energy. However, recently, CEs have been recognized to be associated with many pathological changes, such as atherosclerosis, Wolman Disease, and cancers. This study is aimed to explore the association of cholesteryl esters with prostate cancer. We hypothesized that the expression of genes involved in CE metabolism is differentially regulated between normal and prostate cancer tissues. Two methods were employed in this study: 1) Real-time PCR on 16 fresh-frozen prostatic tissues for the expression of genes related to the pathogenesis of prostate cancer and metabolism of cholesteryl esters; and 2) immunohistochemistry on 165 formalin-fixed and paraffin embedded prostatic tissues for the expression level of ACAT1 and LAL. We found the lipids in category of total lipids, total neutral lipids, cholesteryl esters and free fatty acids are higher in prostatic tissues than in benign prostatic tissues. Among them, cholesteryl esters increased the most (5.8-fold) in prostate cancer. The real-time PCR results indicated that the expression level of genes Pten, LIPA and ABCA1 (but not ACAT1) are obviously lower in high grade than in low grade prostate cancer. It is interesting that the proteins ACAT1 and LAL are reversely expressed: In prostate cancer, ACAT1 is highly expressed, but LAL is not expressed. In contrary, in benign ACAT1 is not expressed, but LAL is highly expressed. Accumulation of cholesterol esters in prostate cancer cells correlate with the progression of prostate cancer. The mechanism of accumulation of cholesteryl esters in prostate cancer cells could be a result of mixed effect of anabolism and catabolism for cholesteryl esters. These results suggest that cholesteryl esters could be potential prognostic biomarkers in differentiating indolent from aggressive cases of prostate cancer, and therapeutic targets for treatment of advanced prostate cancer, including castration resistant prostate cancer.
Reference: Yue, S., Li, J., Lee, H.Y., Shao, T., Song, B., Cheng, L., Masterson, T.A., Liu, X., Ratliff, T.L., Cheng, JX. 2014. Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness. 19 (3):Cell Metabolism. 393-406.
Funder Acknowledgement(s): This work is supported by the Department of Defense through the Prostate Cancer Research Program under Award No.W81XWH-14-1-0151.
Faculty Advisor: Xinchun Zhou,