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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
2001-11-12
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pubmed:abstractText |
The effects of estrogen and anti-estrogen are mediated through the estrogen receptors ERalpha and beta, which function as ligand-induced transcriptional factors. The nonsteroidal anti-estrogen tamoxifen is the most commonly used endocrine in the treatment of all stages of breast cancer in both pre- and postmenopausal women. Several lines of evidence have indicated that tamoxifen promotes association between ERalpha and corepressors N-CoR or silencing mediator for retinoid and thyroid hormone receptor (SMRT). Our results indicate that N-CoR/SMRT recognize and interact with helices H3 and H5 of the ERalpha ligand-binding domain in a 4-hydroxy tamoxifen-dependent manner. The mutant ERalpha(D351Y), derived from a tamoxifen-stimulated tumor and containing an amino acid substitution at position 351 within H3, showed reduced interaction with N-CoR/SMRT and high tamoxifen-induced activation function-1 (AF-1) activity. While the estradiol-dependent transcriptional activity of ERalpha(D351Y) was almost equal to that of wild-type ERalpha, the mutant exhibited higher levels of transcriptional activity in the presence of both E2 and 4-hydroxy tamoxifen compared with wild-type ERalpha. These results may explain the observation that the growth of tumor cells expressing ERalpha(D351Y) can be stimulated by tamoxifen, E2, or both.
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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/Estrogen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Raloxifene,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Selective Estrogen Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
42684-91
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11553641-Amino Acid Sequence,
pubmed-meshheading:11553641-Cell Line,
pubmed-meshheading:11553641-Estrogen Antagonists,
pubmed-meshheading:11553641-Estrogen Receptor alpha,
pubmed-meshheading:11553641-Glutathione Transferase,
pubmed-meshheading:11553641-Histone Deacetylases,
pubmed-meshheading:11553641-Humans,
pubmed-meshheading:11553641-Ligands,
pubmed-meshheading:11553641-Luciferases,
pubmed-meshheading:11553641-Models, Biological,
pubmed-meshheading:11553641-Molecular Sequence Data,
pubmed-meshheading:11553641-Mutation,
pubmed-meshheading:11553641-Plasmids,
pubmed-meshheading:11553641-Protein Binding,
pubmed-meshheading:11553641-Protein Conformation,
pubmed-meshheading:11553641-Protein Structure, Tertiary,
pubmed-meshheading:11553641-Raloxifene,
pubmed-meshheading:11553641-Receptors, Estrogen,
pubmed-meshheading:11553641-Selective Estrogen Receptor Modulators,
pubmed-meshheading:11553641-Tamoxifen,
pubmed-meshheading:11553641-Transcription, Genetic,
pubmed-meshheading:11553641-Transfection,
pubmed-meshheading:11553641-Two-Hybrid System Techniques
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pubmed:year |
2001
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pubmed:articleTitle |
The tamoxifen-responsive estrogen receptor alpha mutant D351Y shows reduced tamoxifen-dependent interaction with corepressor complexes.
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pubmed:affiliation |
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0034, Japan.
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pubmed:publicationType |
Journal Article
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