| Structural alterations of the FAS gene in cutaneous T-cell lymphoma (CTCL). | |
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MedLine Citation:
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PMID: 21036138 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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FAS (TNF receptor superfamily member 6, also known as CD95) plays a major role in T-cell apoptosis and is often dysregulated in CTCL. We searched for structural alterations of the FAS gene with the potential to affect its function. Although several heterozygous FAS promoter single nucleotide polymorphisms (SNPs) were detected, the only homozygous one was the -671 GG SNP present in 24/80 CTCL cases (30%). This SNP maps to an interferon response element activated by STAT-1. EMSA and supershift EMSA showed decreased CTCL nuclear protein/STAT-1 binding to oligonucleotides bearing this SNP. Luciferase reporters showed significantly less interferon-alfa responsive expression by FAS promoter constructs containing this SNP in multiple CTCL lines. Finally, FAS was upregulated by interferon-alfa in wildtype CTCL cells but not those bearing the -671 GG SNP. These findings indicate that many CTCL patients harbor the homozygous FAS promoter -671 GG SNP capable of blunting its response to interferon. This may have implications for CTCL pathogenesis, racial incidence and the response of patients to interferon-alfa therapy. In contrast, functionally significant mutations in FAS coding sequences were detected uncommonly. Among CTCL lines with the potential to serve as models of FAS regulation, FAS-high MyLa had both FAS alleles, FAS-low HH was FAS-hemizygous and FAS-negative SeAx was FAS-null. |
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Authors:
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Jianqiang Wu; Jawed Siddiqui; Minakshi Nihal; Eric C Vonderheid; Gary S Wood |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-29 |
Journal Detail:
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Title: Archives of biochemistry and biophysics Volume: 508 ISSN: 1096-0384 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-18 Completed Date: 2011-05-18 Revised Date: 2012-04-18 |
Medline Journal Info:
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Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: United States |
Other Details:
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Languages: eng Pagination: 185-91 Citation Subset: IM |
Copyright Information:
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Published by Elsevier Inc. |
Affiliation:
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Department of Dermatology, University of Wisconsin and VAMC, Madison, WI, United States. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD95
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genetics* Cell Line Chromosome Aberrations / drug effects Chromosomes, Human, Pair 10 / genetics Gene Expression Regulation, Neoplastic / drug effects Genotype Germ-Line Mutation / drug effects, genetics Humans In Situ Hybridization, Fluorescence Interferon-alpha / pharmacology Lymphoma, T-Cell, Cutaneous / genetics* Polymorphism, Single Nucleotide / drug effects Promoter Regions, Genetic / genetics STAT1 Transcription Factor / metabolism Skin Neoplasms / genetics* Up-Regulation / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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1UL1RR025011/RR/NCRR NIH HHS; UL1 RR025011-01/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/Interferon-alpha; 0/STAT1 Transcription Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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