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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
21
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pubmed:dateCreated |
1995-12-6
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pubmed:abstractText |
Estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines express significantly higher levels of retinoic acid receptor alpha (RAR alpha) (isoform 1) mRNA than ER-negative HBCs. Estradiol enhances RAR alpha mRNA expression in different ER-positive HBCs by 2-3-fold, which in turn results in increased sensitivity of ER-positive HBCs to the growth inhibitory effects of retinoic acid. To investigate the regulatory mechanisms of estradiol-mediated enhancement of RAR alpha mRNA expression, the functional promoter for the human RAR alpha isoform 1 was cloned and used to assess estradiol-mediated promoter-dependent enhancement of firefly luciferase reporter gene activity in transiently transfected ER-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231) HBCs. Deletional promoter constructs were obtained to further delineate the promoter region responsible for estradiol-mediated enhancement of promoter activity. Here, we present evidence that approximately 130 bp of the promoter fragment preceding the transcriptional start site are responsible for estradiol-mediated enhancement of hRAR alpha gene expression. The estradiol-mediated enhancement is dependent on ER binding. Further deletional analysis showed that a promoter sequence of 42 base pairs, located approximately 100 bases upstream of the transcriptional start site, contains elements for estradiol-mediated enhancement. Specific deletion of either the Sp1 motif or mutations in the imperfect half-palindromic estrogen response element motif of this fragment abolish its estradiol responsiveness in transient transfections.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
55
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4999-5006
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7585542-Base Sequence,
pubmed-meshheading:7585542-Breast Neoplasms,
pubmed-meshheading:7585542-Cloning, Molecular,
pubmed-meshheading:7585542-DNA, Complementary,
pubmed-meshheading:7585542-Estradiol,
pubmed-meshheading:7585542-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:7585542-Genes, Reporter,
pubmed-meshheading:7585542-Humans,
pubmed-meshheading:7585542-Luciferases,
pubmed-meshheading:7585542-Molecular Sequence Data,
pubmed-meshheading:7585542-Promoter Regions, Genetic,
pubmed-meshheading:7585542-Receptors, Estrogen,
pubmed-meshheading:7585542-Receptors, Retinoic Acid,
pubmed-meshheading:7585542-Sp1 Transcription Factor,
pubmed-meshheading:7585542-Transfection,
pubmed-meshheading:7585542-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
Estradiol regulation of the human retinoic acid receptor alpha gene in human breast carcinoma cells is mediated via an imperfect half-palindromic estrogen response element and Sp1 motifs.
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pubmed:affiliation |
Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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