Human acyl-CoA : cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma
文献类型:期刊论文
作者 | Song, BL; Wang, CH; Yao, XM; Yang, L; Zhang, WJ; Wang, ZZ; Zhao, XN; Yang, JB; Yang, XY; Inoue, K |
刊名 | BIOCHEMICAL JOURNAL
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出版日期 | 2006 |
卷号 | 394期号:1页码:617-626 |
通讯作者 | Chang, TY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,Ta.Yuan.Chang@dartmouth.edu |
英文摘要 | Humans express two ACAT (acyl-CoA:cholesterol acyltransferase) genes, ACAT1 and ACAT2. ACAT1 is ubiquitously expressed, whereas ACAT2 is primarily expressed in intestinal mucosa and plays an important role in intestinal cholesterol absorption. To investigate the molecular mechanism(s) responsible for the tissue-specific expression of ACAT2, we identified five cis-elements within the human ACAT2 promoter, four for the intestinal-specific transcription factor CDX2 (caudal type homeobox transcription factor 2). and one for the transcription factor HNF1 alpha (hepatocyte nuclear factor 1 alpha). Results of luciferase reporter and electrophoretic mobility shift assays show that CDX2 and HNF1 alpha exert a synergistic effect, enhancing the ACAT2 promoter activity through binding to these cis-elements. In undifferentiated Caco-2 cells, the ACAT2 expression is increased when exogenous CDX2 and/or HNF1 alpha are expressed by co-transfection. In differentiated Caco-2 cells, the ACAT2 expression significantly decreases when the endogenous CDX2 or HNF1 alpha expression is suppressed by using RNAi (RNA interference) technology. The expression levels of CDX2, HNF1 alpha, and ACAT2 are all greatly increased when the Caco-2 cells differentiate to become intestinal-like cells. These results provide a molecular mechanism for the tissue-specific expression of ACAT2 in intestine. In normal adult human liver, CDX2 expression is not detectable and the ACAT2 expression is very low. In the hepatoma cell line HepG2 the CDX2 expression is elevated, accounting for its elevated ACAT2 expression. A high percentage (seven Of fourteen) of liver samples from patients affected with hepatocellular carcinoma exhibited elevated ACAT2 expression. Thus, the elevated ACAT2 expression may serve as a new biomarker for certain form(s) of hepatocellular carcinoma. |
学科主题 | Biochemistry & Molecular Biology |
类目[WOS] | Biochemistry & Molecular Biology |
关键词[WOS] | HEPATOCYTE NUCLEAR FACTOR-1-ALPHA ; E-DEFICIENT MICE ; TRANSCRIPTIONAL ACTIVATION ; HOMEODOMAIN PROTEINS ; ACAT INHIBITOR ; HUMAN LIVER ; FACTOR-I ; MOUSE ; LOCALIZATION ; MACROPHAGES |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000236137000009 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/1832] ![]() |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Song, BL,Wang, CH,Yao, XM,et al. Human acyl-CoA : cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma[J]. BIOCHEMICAL JOURNAL,2006,394(1):617-626. |
APA | Song, BL.,Wang, CH.,Yao, XM.,Yang, L.,Zhang, WJ.,...&Li, BL.(2006).Human acyl-CoA : cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma.BIOCHEMICAL JOURNAL,394(1),617-626. |
MLA | Song, BL,et al."Human acyl-CoA : cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma".BIOCHEMICAL JOURNAL 394.1(2006):617-626. |
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