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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2010-1-14
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pubmed:abstractText |
Approximately 80% of breast cancers express the estrogen receptor-alpha (ERalpha) and are treated with anti-estrogens. Resistance to these agents is a major cause of mortality. We have shown that estrogen inhibits Notch, whereas anti-estrogens or estrogen withdrawal activate Notch signaling. Combined inhibition of Notch and estrogen signaling has synergistic effects in ERalpha-positive breast cancer models. However, the mechanisms whereby Notch-1 promotes the growth of ERalpha-positive breast cancer cells are unknown. Here, we demonstrate that Notch-1 increases the transcription of ERalpha-responsive genes in the presence or absence of estrogen via a novel chromatin crosstalk mechanism. Our data support a model in which Notch-1 can activate the transcription of ERalpha-target genes via IKKalpha-dependent cooperative chromatin recruitment of Notch-CSL-MAML1 transcriptional complexes (NTC) and ERalpha, which promotes the recruitment of p300. CSL binding elements frequently occur in close proximity to estrogen-responsive elements (EREs) in the human and mouse genomes. Our observations suggest that a hitherto unknown Notch-1/ERalpha chromatin crosstalk mediates Notch signaling effects in ERalpha-positive breast cancer cells and contributes to regulate the transcriptional functions of ERalpha itself.
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pubmed:grant |
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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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/EP300 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin J Recombination...,
http://linkedlifedata.com/resource/pubmed/chemical/MAML1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/RBPJ protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonyl-leucyl-leucyl-norl...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1476-5594
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
201-13
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pubmed:meshHeading |
pubmed-meshheading:19838210-Animals,
pubmed-meshheading:19838210-Blotting, Western,
pubmed-meshheading:19838210-Breast Neoplasms,
pubmed-meshheading:19838210-Cell Line, Tumor,
pubmed-meshheading:19838210-DNA-Binding Proteins,
pubmed-meshheading:19838210-E1A-Associated p300 Protein,
pubmed-meshheading:19838210-Estrogen Antagonists,
pubmed-meshheading:19838210-Estrogen Receptor alpha,
pubmed-meshheading:19838210-Female,
pubmed-meshheading:19838210-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19838210-Humans,
pubmed-meshheading:19838210-I-kappa B Kinase,
pubmed-meshheading:19838210-Immunoglobulin J Recombination Signal Sequence-Binding...,
pubmed-meshheading:19838210-Mammary Neoplasms, Experimental,
pubmed-meshheading:19838210-Mice,
pubmed-meshheading:19838210-Mice, Inbred BALB C,
pubmed-meshheading:19838210-Mice, Nude,
pubmed-meshheading:19838210-Oligopeptides,
pubmed-meshheading:19838210-Promoter Regions, Genetic,
pubmed-meshheading:19838210-Receptor, Notch1,
pubmed-meshheading:19838210-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19838210-Tamoxifen,
pubmed-meshheading:19838210-Transcription, Genetic,
pubmed-meshheading:19838210-Transcription Factors,
pubmed-meshheading:19838210-Xenograft Model Antitumor Assays
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pubmed:year |
2010
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pubmed:articleTitle |
Notch-1 activates estrogen receptor-alpha-dependent transcription via IKKalpha in breast cancer cells.
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pubmed:affiliation |
Breast Cancer Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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