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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
29
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pubmed:dateCreated |
2003-7-14
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pubmed:abstractText |
The effects of estrogen and anti-estrogen are mediated through the estrogen receptors (ER) alpha and beta, which function as ligand-induced transcriptional factors. Recently, one of the phthalate esters, n-butylbenzyl phthalate (BBP), has been shown to induce estrogen receptor-mediated responses. By using the truncated types of ER mutants, we revealed that activation function-1 (AF-1) activity was necessary for the BBP-dependent transactivation function of ERalpha. AF-1 is also known to be responsible for the partial agonistic activity of tamoxifen. Whereas tamoxifen exhibits an anti-estrogenic effect on proliferation of the MCF-7 breast cancer cell line, BBP showed an estrogenic effect on MCF-7 to stimulate proliferation. In vivo and in vitro binding assays revealed that whereas 4-hydroxytamoxifen (OHT) induced binding of ERalpha to both an AF-1 coactivator complex (p68/p72 and p300) and corepressor complexes (N-CoR/SMRT), BBP selectively enhanced the binding to the AF-1 coactivators. We also showed that the transcriptional activity of OHT-bound ERalpha was modulated by the ratio between the AF-1 coactivator and corepressor complexes. Expression of a dominant-negative type of N-CoR inhibited the interaction between OHT-bound ERalpha and N-CoR/SMRT and enhanced the transcriptional activity of OHT-bound ERalpha. Furthermore, the cell growth of MCF-7 stably expressing the dominant-negative type of N-CoR was enhanced by the addition of OHT. These results indicated that fully activated AF-1 induces the stimulation of breast cancer growth and that the ratio between AF-1 coactivators and corepressors plays a key role to prevent proliferation of tumor by tamoxifen.
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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/4-hydroxytamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/IFNGR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ifngr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phthalic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/butylbenzyl phthalate
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:BabaTadashiT,
pubmed-author:FujitaTetsuoT,
pubmed-author:KatoShigeakiS,
pubmed-author:KawabeYoh-IchiY,
pubmed-author:KitadaLinaL,
pubmed-author:KobayashiYokoY,
pubmed-author:MurayamaAkikoA,
pubmed-author:TakashimaHisashigeH,
pubmed-author:TateishiYukiyoY,
pubmed-author:WadaOsamuO,
pubmed-author:YamamotoYasujiY,
pubmed-author:YanagisawaJunnJ,
pubmed-author:YanoTetsuT
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26704-14
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12738788-3T3 Cells,
pubmed-meshheading:12738788-Animals,
pubmed-meshheading:12738788-Binding, Competitive,
pubmed-meshheading:12738788-Breast Neoplasms,
pubmed-meshheading:12738788-Cell Division,
pubmed-meshheading:12738788-Estrogen Receptor alpha,
pubmed-meshheading:12738788-Female,
pubmed-meshheading:12738788-Humans,
pubmed-meshheading:12738788-Mice,
pubmed-meshheading:12738788-Neoplasms, Hormone-Dependent,
pubmed-meshheading:12738788-Phthalic Acids,
pubmed-meshheading:12738788-Protein Binding,
pubmed-meshheading:12738788-Protein Structure, Tertiary,
pubmed-meshheading:12738788-Receptors, Estrogen,
pubmed-meshheading:12738788-Receptors, Interferon,
pubmed-meshheading:12738788-Repressor Proteins,
pubmed-meshheading:12738788-Tamoxifen,
pubmed-meshheading:12738788-Transcriptional Activation,
pubmed-meshheading:12738788-Transfection,
pubmed-meshheading:12738788-Tumor Cells, Cultured,
pubmed-meshheading:12738788-Two-Hybrid System Techniques
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pubmed:year |
2003
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pubmed:articleTitle |
Full activation of estrogen receptor alpha activation function-1 induces proliferation of breast cancer cells.
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pubmed:affiliation |
Institute of Applied Biochemistry, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8572, Japan.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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