| pubmed-article:21041310 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C1512505 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C0034804 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C1516170 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C0699900 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C0243125 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C2003941 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C1999216 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C1328819 | lld:lifeskim |
| pubmed-article:21041310 | lifeskim:mentions | umls-concept:C2349975 | lld:lifeskim |
| pubmed-article:21041310 | pubmed:issue | 53 | lld:pubmed |
| pubmed-article:21041310 | pubmed:dateCreated | 2010-12-27 | lld:pubmed |
| pubmed-article:21041310 | pubmed:abstractText | The mechanisms responsible for 17?-estradiol (E(2))-stimulated breast cancer growth and development of resistance to tamoxifen and other estrogen receptor ? (ER?) antagonists are not fully understood. We describe a new tool for dissecting ER? action in breast cancer, p-fluoro-4-(1,2,3,6,-tetrahydro-1,3-dimethyl-2-oxo-6-thionpurin-8-ylthio) (TPSF), a potent small-molecule inhibitor of estrogen receptor ? that does not compete with estrogen for binding to ER?. TPSF noncompetitively inhibits estrogen-dependent ER?-mediated gene expression with little inhibition of transcriptional activity by NF-?B or the androgen or glucocorticoid receptor. TPSF inhibits E(2)-ER?-mediated induction of the proteinase inhibitor 9 gene, which is activated by ER? binding to estrogen response element DNA, and the cyclin D1 gene, which is induced by tethering ER? to other DNA-bound proteins. TPSF inhibits anchorage-dependent and anchorage-independent E(2)-ER?-stimulated growth of MCF-7 cells but does not inhibit growth of ER-negative MDA-MB-231 breast cancer cells. TPSF also inhibits ER?-dependent growth in three cellular models for tamoxifen resistance; that is, 4-hydroxytamoxifen-stimulated MCF7ER?HA cells that overexpress ER?, fully tamoxifen-resistant BT474 cells that have amplified HER-2 and AIB1, and partially tamoxifen-resistant ZR-75 cells. TPSF reduces ER? protein levels in MCF-7 cells and several other cell lines without altering ER? mRNA levels. The proteasome inhibitor MG132 abolished down-regulation of ER? by TPSF. Thus, TPSF affects receptor levels at least in part due to its ability to enhance proteasome-dependent degradation of ER?. TPSF represents a novel class of ER inhibitor with significant clinical potential. | lld:pubmed |
| pubmed-article:21041310 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041310 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041310 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041310 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041310 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21041310 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041310 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21041310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21041310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21041310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041310 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21041310 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:21041310 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:WilsonElizabe... | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:NordeenSteven... | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:HergenrotherP... | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:ShapiroDavid... | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:SchiffRachelR | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:MaoChengjianC | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:CherianMilu... | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:AninyeIrene... | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:KretzerNicole... | lld:pubmed |
| pubmed-article:21041310 | pubmed:author | pubmed-author:ReynoldsPhili... | lld:pubmed |
| pubmed-article:21041310 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21041310 | pubmed:day | 31 | lld:pubmed |
| pubmed-article:21041310 | pubmed:volume | 285 | lld:pubmed |
| pubmed-article:21041310 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21041310 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21041310 | pubmed:pagination | 41863-73 | lld:pubmed |
| pubmed-article:21041310 | pubmed:dateRevised | 2011-2-14 | lld:pubmed |
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| pubmed-article:21041310 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:21041310 | pubmed:articleTitle | A noncompetitive small molecule inhibitor of estrogen-regulated gene expression and breast cancer cell growth that enhances proteasome-dependent degradation of estrogen receptor {alpha}. | lld:pubmed |
| pubmed-article:21041310 | pubmed:affiliation | Department of Biochemistry, University of Illinois, Urbana, Illinois 61801-3602, USA. | lld:pubmed |
| pubmed-article:21041310 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21041310 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:21041310 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| entrez-gene:2099 | entrezgene:pubmed | pubmed-article:21041310 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:21041310 | lld:entrezgene |
