Source:http://linkedlifedata.com/resource/pubmed/id/10597280
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
48
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pubmed:dateCreated |
2000-1-6
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pubmed:abstractText |
Retinoic acid receptor-beta (RAR beta) and signal transducer and activator of transcription 1 (STAT1) are important mediators of the antiproliferative and apoptotic actions of retinoids and cytokines/growth factors, respectively. Expression of both RAR beta and STAT1 is lost in most breast cancer cell lines but it can be induced by retinoids in estrogen receptor-positive cells. We investigated a possible functional connection between these two mediators and present evidence supporting RAR beta as a tumor suppressor. First, by using different receptor-selective retinoids, we demonstrated that RAR beta induction in MCF-7 cells by all-trans-retinoic acid (atRA) was associated with the activation of STAT1 gene transcription. The direct involvement of RAR beta in atRA-induced STAT1 gene activation was further demonstrated by showing that transfection with an anti-sense RAR beta construct blocked atRA-induced STAT1 expression in MCF-7 cells whereas introduction of a sense-RAR beta construct resulted in STAT1 induction by atRA in MDA-MB 231 cells. In addition, we showed that STAT1 was phosphorylated/activated under atRA treatment of MCF-7 cells; this process required the involvement of RAR beta and protein synthesis. STAT1 phosphorylation/activation was accompanied by increased tyrosine kinase activity that was not due to the activation of JAK1, JAK2 or Tyk 2, suggesting the possible involvement of an unidentified tyrosine kinase.
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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 Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6725-32
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10597280-Base Sequence,
pubmed-meshheading:10597280-Breast Neoplasms,
pubmed-meshheading:10597280-DNA Primers,
pubmed-meshheading:10597280-DNA-Binding Proteins,
pubmed-meshheading:10597280-Dose-Response Relationship, Drug,
pubmed-meshheading:10597280-Humans,
pubmed-meshheading:10597280-Phosphorylation,
pubmed-meshheading:10597280-Protein-Tyrosine Kinases,
pubmed-meshheading:10597280-Receptors, Retinoic Acid,
pubmed-meshheading:10597280-STAT1 Transcription Factor,
pubmed-meshheading:10597280-Signal Transduction,
pubmed-meshheading:10597280-Trans-Activators,
pubmed-meshheading:10597280-Tretinoin,
pubmed-meshheading:10597280-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
The induction and activation of STAT1 by all-trans-retinoic acid are mediated by RAR beta signaling pathways in breast cancer cells.
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pubmed:affiliation |
Nutrition Department, Pennsylvania State University, University Park 16802, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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