TitleAlpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma
AuthorsWang, Shanshan
Jiang, Wei
Chen, Xiangmei
Zhang, Chao
Li, Hui
Hou, Wenting
Liu, Zhongmin
McNutt, Michael A.
Lu, Fengmin
Li, Gang
AffiliationPeking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China.
Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biol Micro2, Beijing 100191, Peoples R China.
Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pathol, Beijing 100191, Peoples R China.
Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100191, Peoples R China.
KeywordsFn14
Hepatoma
All trans retinoic acid
Nuclear receptor
Transcription regulation
MU-OPIOID RECEPTOR
INDUCED CELL-DEATH
MULTIPLE PATHWAYS
TWEAK
EXPRESSION
GENE
LYMPHOCYTES
MECHANISM
APOPTOSIS
NECROSIS
Issue Date2012
Publisher肝脏病杂志
CitationJOURNAL OF HEPATOLOGY.2012,57,(2),322-329.
AbstractBackground & 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.
URIhttp://hdl.handle.net/20.500.11897/192011
ISSN0168-8278
DOI10.1016/j.jhep.2012.03.029
IndexedSCI(E)
PubMed
Appears in Collections:基础医学院

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