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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2004-5-3
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pubmed:abstractText |
The efficacy of tamoxifen in breast cancer treatment only lasts a few years and the tumor eventually recurs. We performed selective subtractive hybridization to isolate mRNAs that were differentially expressed in MCF-7 derived cells, in which resistance had been induced through long-term culture in the presence of hydroxytamoxifen (OHT). Among the 15 mRNAs found to be overexpressed, we focused on Immediate early gene X-1 (IEX-1) mRNA because of the recognized contribution of its expression to apoptosis or cell cycle progression, depending on the cell type and culture conditions. We observed that IEX-1 expression was stimulated by OHT, that the degree of increase was greater in resistant cells (four-fold versus 1.5-fold) and that this OHT regulation was estrogen receptor dependent. A detailed study of the IEX-1 promoter indicated that it involved NF-kappaB. Our cells were not cross-resistant to faslodex, a pure antiestrogen, which moreover was inefficient in regulating IEX-1 expression. Altogether, our data suggest that the greater IEX-1 expression in OHT resistant cells is related to their ability to grow in the presence of OHT. Knowledge on the capacity of OHT to stimulate gene expression and its NF-kappaB dependence should contribute to a better understanding of tamoxifen pharmacology and allow new drug strategies to be designed that would delay antiestrogen resistance acquisition.
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/IER3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/hydroxytamoxifen
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0960-0760
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
247-59
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15120418-Apoptosis Regulatory Proteins,
pubmed-meshheading:15120418-Base Sequence,
pubmed-meshheading:15120418-Blotting, Northern,
pubmed-meshheading:15120418-Breast Neoplasms,
pubmed-meshheading:15120418-Cloning, Molecular,
pubmed-meshheading:15120418-DNA Primers,
pubmed-meshheading:15120418-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15120418-Genes, Immediate-Early,
pubmed-meshheading:15120418-Humans,
pubmed-meshheading:15120418-Immediate-Early Proteins,
pubmed-meshheading:15120418-Membrane Proteins,
pubmed-meshheading:15120418-Neoplasm Proteins,
pubmed-meshheading:15120418-Promoter Regions, Genetic,
pubmed-meshheading:15120418-RNA, Messenger,
pubmed-meshheading:15120418-Tamoxifen,
pubmed-meshheading:15120418-Tetradecanoylphorbol Acetate,
pubmed-meshheading:15120418-Transcription, Genetic,
pubmed-meshheading:15120418-Tumor Suppressor Protein p53
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pubmed:year |
2004
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pubmed:articleTitle |
Immediate early gene X-1 (IEX-1), a hydroxytamoxifen regulated gene with increased stimulation in MCF-7 derived resistant breast cancer cells.
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pubmed:affiliation |
INSERM U.540, 60 Rue de Navacelles, Montpellier 34090, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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