Understanding the function, expression and regulatory mechanism of Liver X Receptor genes in human prostate cancer

• Main Authors: Tzu Yi Li, 李姿儀
• Other Authors: H. H. Juang
• Format: Others
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/78220090996800847966

碩士 === 長庚大學 === 生物醫學研究所 === 99 === Liver X receptors (LXR and LXR) belong to the nuclear receptor superfamily. LXRs are important regulators of cholesterol, fatty acid and glucose homeostasis. However the function, expression and regulation mechanisms of the LXRs gene in prostate carcinoma cells remain unknown. Results from 3H-thymidine incorporation assay and cell invasion assay revealed that knock-down either LXR or LXRgene increased cell proliferation and the ability of invasion in human prostate carcinoma, LNCaP cells. Consistently, we also showed that overexpression LXRβ gene could significantly inhibit tumor growth in xenografts animal study. Immunoblot assay indicated that knock down LXRs gene decreased the protein levels of E-cadherin but increased vimentin and β-catenin. Glucose upregulated the gene expression of LXR; however, both T0901317 and GW3965 upregulated fatty acid synthase but not mitochondrial aconitase suggesting an effect of LXR agonists on lipid metabolism. Enzyme linked immunosorbent assay (ELISA) and immunoblot assays indicated that T0901317 decreased prostate-specific antigen (PSA) gene expression; however, GW3965 upregulated PSA gene expression. GW3965 increases PSA promoter activity is dependent on the expression of AR and the inducing effect of GW3965 on PSA gene expression was blocked by epigallocatechin gallate (EGCG). As compared with scrambled shRNA transduced-LNCaP cells, shRNA knockdown of LXR but not LXR attenuated the effect of T0901317 on PSA gene expression. Our results provide the notion of function of LXRs in tumorigenesis and metabolism and prove that divergent effect of LXR agonists on the PSA expression in prostate carcinoma cells.