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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
1995-3-13
|
| pubmed:abstractText |
We show that some transcriptionally inactive human estrogen receptor (ER) mutants can be activated by 17 beta-estradiol (E2), and sometimes by antiestrogens, in the presence of elevated levels of intracellular cAMP. ER-deficient Chinese hamster ovary or 3T3 mouse fibroblast cells were transfected with mutant ERs (the point mutant L540Q, the frameshift mutant S554fs, or the carboxy-terminal truncated receptor ER1-530) and various estrogen response element-containing reporter genes. Individual treatments with E2, the antiestrogens trans-hydroxytamoxifen and ICI 164,384, or with 3-isobutyl-1-methyl-xanthine plus cholera toxin (IBMX plus CT) which raise intracellular cAMP, generally do not activate the mutant receptors. However, cotreatment with IBMX/CT and one of the three ligands (E2, trans-hydroxytamoxifen, or ICI164,384) results in the unexpected recovery of strong activation of the L540Q or S554fs receptors, the magnitude of which is dependent upon promoter- and cell-contexts. Unlike L540Q and S554fs, the transcriptionally inactive ER1-530 is not activated by any combination of ligands and IBMX/CT. These data demonstrate that some ER mutants that form transcriptionally nonproductive ER-E2 complexes can be successfully activated by the combination of an agonist or antagonist ligand and an agent thought to act via phosphorylation pathways. Also highlighted is the promoter- and cell-specific nature of the transcriptional response to different ligand-ER complexes. Lastly, the enhanced transcriptional activity of wild type ER and some ER mutants in the presence of antiestrogens and elevated intracellular cAMP may provide a partial explanation of the ability of some estrogen-dependent human breast tumors to resist antiestrogen therapies currently employed.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0888-8809
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
8
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1397-406
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7531820-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:7531820-3T3 Cells,
pubmed-meshheading:7531820-Animals,
pubmed-meshheading:7531820-Base Sequence,
pubmed-meshheading:7531820-CHO Cells,
pubmed-meshheading:7531820-Cholera Toxin,
pubmed-meshheading:7531820-Cricetinae,
pubmed-meshheading:7531820-Cyclic AMP,
pubmed-meshheading:7531820-Estradiol,
pubmed-meshheading:7531820-Estrogen Antagonists,
pubmed-meshheading:7531820-Genes, Reporter,
pubmed-meshheading:7531820-Humans,
pubmed-meshheading:7531820-Mice,
pubmed-meshheading:7531820-Molecular Sequence Data,
pubmed-meshheading:7531820-Mutagenesis,
pubmed-meshheading:7531820-Mutation,
pubmed-meshheading:7531820-Receptors, Estrogen,
pubmed-meshheading:7531820-Transcription, Genetic,
pubmed-meshheading:7531820-Transfection
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Activation of transcriptionally inactive human estrogen receptors by cyclic adenosine 3',5'-monophosphate and ligands including antiestrogens.
|
| pubmed:affiliation |
Department of Physiology and Biophysics, University of Illinois, Urbana 61801.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|