IR@PKUHSC  > 北京大学基础医学院
学科主题基础医学
Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma
Wang, Shanshan1; Jiang, Wei1; Chen, Xiangmei2; Zhang, Chao1; Li, Hui1; Hou, Wenting1; Liu, Zhongmin1; McNutt, Michael A.3; Lu, Fengmin2; Li, Gang1
关键词Fn14 Hepatoma All trans retinoic acid Nuclear receptor Transcription regulation
刊名JOURNAL OF HEPATOLOGY
2012-08-01
DOI10.1016/j.jhep.2012.03.029
57期:2页:322-329
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology
研究领域[WOS]Gastroenterology & Hepatology
关键词[WOS]MU-OPIOID RECEPTOR ; INDUCED CELL-DEATH ; MULTIPLE PATHWAYS ; TWEAK ; EXPRESSION ; GENE ; LYMPHOCYTES ; MECHANISM ; APOPTOSIS ; NECROSIS
英文摘要

Background & Aims: The function of cytoplasmic AFP as a regulatory factor in the growth of tumor cells has been well defined. However, its precise mechanism of action and its clinical significance remain to be worked out.

Methods: Specimens from HCC patients were analyzed by using immunohistochemistry, co-immunoprecipitation (CoIP), and chromatin immunoprecipitation (ChIP) assays to evaluate the role of AFP in RAR signaling-mediated carcinogenesis. Quantitative real-time reverse transcription PCR, Western blotting, confocal microscopy, CoIP, GST pull-down, siRNA, gene transfection, and ChIP assays were also used for analysis of cell lines.

Results: RAR is able to interact with cytoplasmic AFP and binds to the element of the regulatory region of the Fn14 gene in the neoplastic tissue of HCC patients. An assay of hepatocyte cell lines of differing AFP expression showed that cytoplasmic AFP is able to block ATRA-induced nuclear translocation of RAR and expression of the Fn14 gene. Knockdown of AFP in siRNA-transfected HepG2 and Bel7402 cells led to greater binding of RAR to its response element. The expression of the Fn14 gene was therefore up regulated as reflected by increases in mRNA and protein levels. Conversely, transfection of HLE and L02 cells (AFP negative) with the afp gene resulted in apparent reduction of RAR binding to DNA and Fn14 protein.

Conclusions: Demonstration of the involvement of cytoplasmic AFP in RAR-mediated expression of the Fn14 gene strongly indicates AFP plays a signal molecule-like role in the regulation of hepatocellular carcinoma growth. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000307685300017
项目编号81072710 ; 7101006
资助机构National Natural Science Foundation of China ; Beijing Natural Science Foundation
引用统计
被引频次:22[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66570
专题北京大学基础医学院
北京大学第二临床医学院_产科
作者单位1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biol Micro2, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pathol, Beijing 100191, Peoples R China
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GB/T 7714
Wang, Shanshan,Jiang, Wei,Chen, Xiangmei,et al. Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma[J]. JOURNAL OF HEPATOLOGY,2012,57(2):322-329.
APA Wang, Shanshan.,Jiang, Wei.,Chen, Xiangmei.,Zhang, Chao.,Li, Hui.,...&Li, Gang.(2012).Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma.JOURNAL OF HEPATOLOGY,57(2),322-329.
MLA Wang, Shanshan,et al."Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma".JOURNAL OF HEPATOLOGY 57.2(2012):322-329.
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