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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2001-3-22
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pubmed:abstractText |
Previous studies showed that TGF-beta down-regulates aryl hydrocarbon (AhR) expression in human lung carcinoma cells A549. Here we analyzed the molecular mechanisms by which TGF-beta modulates AhR expression. A 5799-nucleotide 5'-flanking region of human AhR gene was isolated. Transient transfection studies of full-length (hAhRP) and deletion promoter constructs indicate the requirement of a cis-regulatory element encompassing -1980 to -1892 for full constitutive activity. Basal hAhRP activity occurs in a cell-specific manner; human hepatoma HepG2 cells possess a 10-fold higher activity compared with A549 cells. TGF-beta exerts cell-specific effects on hAhRP activity. Treatment of cells with 100 pM TGF-beta leads to a 50% inhibition in A549 and a 3-fold induction in HepG2 cells. Deletion mutagenesis identified a TGF-beta-responsive sequence containing a functional conserved Smad-binding element. Transient overexpression of Smad 2, 3, and 4 indicates that these signal transducers modulate hAhRP activity. The down-regulation of AhR by TGF-beta is modulated by 5'-TG-3'-interacting factor (TGIF). Transient overexpression of TGIF in MDA-MB231 and HepG2 cells led to inhibition of hAhRP activity and a similar decrease of AhR mRNA expression. Our findings indicate that Smad proteins are involved in the cell-specific regulation of AhR expression by TGF-beta.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Activin Receptors, Type I,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Aryl Hydrocarbon,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad4 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor,
http://linkedlifedata.com/resource/pubmed/chemical/TGIF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0026-895X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
59
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
716-24
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11259615-5' Untranslated Regions,
pubmed-meshheading:11259615-Activin Receptors, Type I,
pubmed-meshheading:11259615-Binding Sites,
pubmed-meshheading:11259615-Carcinoma,
pubmed-meshheading:11259615-DNA-Binding Proteins,
pubmed-meshheading:11259615-Dose-Response Relationship, Drug,
pubmed-meshheading:11259615-Down-Regulation,
pubmed-meshheading:11259615-Homeodomain Proteins,
pubmed-meshheading:11259615-Humans,
pubmed-meshheading:11259615-Liver Neoplasms,
pubmed-meshheading:11259615-Lung Neoplasms,
pubmed-meshheading:11259615-Mutagenesis, Site-Directed,
pubmed-meshheading:11259615-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11259615-RNA, Messenger,
pubmed-meshheading:11259615-Receptors, Aryl Hydrocarbon,
pubmed-meshheading:11259615-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:11259615-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:11259615-Repressor Proteins,
pubmed-meshheading:11259615-Smad2 Protein,
pubmed-meshheading:11259615-Smad3 Protein,
pubmed-meshheading:11259615-Smad4 Protein,
pubmed-meshheading:11259615-Trans-Activators,
pubmed-meshheading:11259615-Transfection,
pubmed-meshheading:11259615-Transforming Growth Factor beta,
pubmed-meshheading:11259615-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Cell-specific regulation of human aryl hydrocarbon receptor expression by transforming growth factor-beta(1).
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pubmed:affiliation |
Department of Experimental Toxicology, Medical Institute of Environmental Hygiene at the Heinrich-Heine-University, Düsseldorf, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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