Document Detail


All-trans retinoic acid induces XAF1 expression through an interferon regulatory factor-1 element in colon cancer.
MedLine Citation:
PMID:  16530516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is a novel tumor suppressor and interferon (IFN)-stimulated gene. All-trans retinoic acid (ATRA) exerts an antiproliferative effect on tumor cells through up-regulation of IFN regulatory factor 1 (IRF-1) and the downstream IFN-stimulated genes. The aim of this study was to determine the effect and mechanism of ATRA on XAF1 expression and the role of XAF1 in ATRA-induced growth inhibition in colon cancer. METHODS: Gene expression is detected by reverse-transcription polymerase chain reaction and immunoblotting. The transcription activity of XAF1 promoter is examined by luciferase reporter assay. The activity of IFN regulatory factor binding element (IRF-E) is assessed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Cell growth is evaluated by both in vitro and in vivo in nude mice xenografts. RESULTS: IFN-alfa stimulates XAF1 promoter activity in the colon cancer cells Lovo and SW1116 dose-dependently. An IRF-1 binding element (IRF-E-XAF1) is found in the -30 to -38 nucleotide region upstream of the ATG initiator codon of the XAF1 gene. Site-directed mutagenesis of IRF-E-XAF1 abrogates native and IFN-induced promoter activity and binding capacity. ATRA induces XAF1 expression both in vitro and in vivo through interaction with IRF-E-XAF1. Overexpression of XAF1 increases cell susceptibility to ATRA-induced growth suppression both in vitro and in vivo. Furthermore, the effect of ATRA on XAF1 expression is independent of the promoter methylation and the subcellular distribution of XIAP. CONCLUSIONS: XAF1 participates in ATRA-induced growth suppression through IRF-1-mediated transcriptional regulation.
Authors:
Jide Wang; Ying Peng; Yun Wei Sun; Hua He; Senlin Zhu; Xiaomeng An; Ming Li; Marie C M Lin; Bing Zou; Harry Hua-Xiang Xia; Bo Jiang; Annie O O Chan; Man Fung Yuen; Hsiang Fu Kung; Benjamin C Y Wong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gastroenterology     Volume:  130     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-13     Completed Date:  2006-04-06     Revised Date:  2010-09-10    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  747-58     Citation Subset:  AIM; IM    
Affiliation:
Institute for Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Colonic Neoplasms / drug therapy,  metabolism*
CpG Islands
DNA Methylation
Gene Expression Regulation / drug effects
Humans
Interferon Regulatory Factor-1 / physiology*
Mice
Mutagenesis, Site-Directed
Neoplasm Proteins / genetics*,  physiology
Promoter Regions, Genetic
Transcription Initiation Site
Tretinoin / pharmacology*
Chemical
Reg. No./Substance:
0/Interferon Regulatory Factor-1; 0/Neoplasm Proteins; 0/XAF1 protein, human; 302-79-4/Tretinoin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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