Farnesoid X receptor expression is reduced in human hepatocellular carcinoma

作     者：Zhang Wenyu Chen Ping Zhao Yuanyin Lou Guiyu 

作者机构：Department of EndocrinologyPeople's Hospital of ZhengzhouZhengzhou 450003China Department of Hepatobiliary SurgeryDaping Hospital Institute of Surgery ResearchThird Military Medical UniversityChongqing 400042China Department of BiochemistryCollege of Basic Medical SciencesThird Military Medical UniversityChongqing 400038China 

出 版 物：《Journal of Medical Colleges of PLA(China)》 (中国人民解放军军医大学学报（英文版）)

年 卷 期：2012年第27卷第1期

页      面：1-9页

学科分类：0710[理学-生物学] 083002[工学-环境工程] 0830[工学-环境科学与工程（可授工学、理学、农学学位）] 07[理学] 08[工学] 09[农学] 0903[农学-农业资源与环境] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 0713[理学-生态学] 

基　　金：Supported by the National Natural Science Foundation of China(30600299) 

主　　题：Farnesoid X receptor Human hepatocellular carcinoma Pro-inflammatory cytokines 

摘      要：Farnesoid X receptor (FXR, NR1H4) is a member of nuclear hormone receptor superfamily. Previously studies showed that FXR-/- mice spontaneously developed liver tumors when they aged, however, the relevance of which to human hepatocellular carcinoma (HCC) is unclear. The aim of this study is to observe whether FXR expression is also downregulated in HCC and discuss the mechanism of the reduced FXR expression in HCC. Expression of FXR and small heterodimer partner (SHP) was measured by real-time PCR and immunohistochemical technique. Effect of pro-inflammatory cytokines on expression of FXR and its promoter activity were determined in primary hepatocytes or HepG2 and Huh7 cell lines. Our results showed that expression of FXR and its target gene SHP in human HCC was strongly downregulated compared to the normal liver tissues. In addition, pro-inflammatory cytokines were able to decrease FXR expression by inhibiting the FXR promoter activity. In conclusion this work demonstrates FXR expression is strongly downregulated in human HCC, which may be caused by decreased FXR promoter activity, suggesting a potential role of FXR in human HCC development.