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rdf:type |
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lifeskim:mentions |
umls-concept:C0006142,
umls-concept:C0034840,
umls-concept:C0040648,
umls-concept:C0086597,
umls-concept:C0205202,
umls-concept:C0279025,
umls-concept:C0458003,
umls-concept:C0678723,
umls-concept:C0683598,
umls-concept:C1415675,
umls-concept:C1704675
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pubmed:issue |
4
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pubmed:dateCreated |
2010-2-16
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pubmed:abstractText |
Mechanisms of acquired resistance to endocrine therapy in breast cancer, a major clinical challenge, are poorly understood. We have used a mass spectrometry-based screen to identify proteins that are associated with the endocrine-resistant phenotype. In this study, we report the identification of a novel pathway of resistance to endocrine therapy involving interactions of the developmental transcription HOXC11 with the steroid receptor coactivator protein SRC-1, which is a strong predictor of reduced disease-free survival in breast cancer patients. HOXC11 and SRC-1 cooperate to regulate expression of the calcium-binding protein S100beta in resistant breast cancer cells. Nuclear HOXC11 and S100beta were found to strongly predict poor disease-free survival in breast cancer patients (n = 560; hazard ratios: 5.79 and 5.82, respectively; P < 0.0001). Elevated serum levels of S100beta detected in patients also predicted reduced disease-free survival (n = 80; hazard ratio: 5.3; P = 0.004). Our findings define a biomolecular interaction network that drives an adaptive response to endocrine therapy with negative consequences for survival in breast cancer.
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pubmed:commentsCorrections |
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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/Antineoplastic Agents, Hormonal,
http://linkedlifedata.com/resource/pubmed/chemical/HOXC11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NCOA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 1,
http://linkedlifedata.com/resource/pubmed/chemical/S-100 calcium-binding protein beta...,
http://linkedlifedata.com/resource/pubmed/chemical/S100 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1538-7445
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1585-94
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pubmed:dateRevised |
2010-4-16
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pubmed:meshHeading |
pubmed-meshheading:20145129-Antineoplastic Agents, Hormonal,
pubmed-meshheading:20145129-Breast Neoplasms,
pubmed-meshheading:20145129-Case-Control Studies,
pubmed-meshheading:20145129-Disease-Free Survival,
pubmed-meshheading:20145129-Drug Resistance, Neoplasm,
pubmed-meshheading:20145129-Female,
pubmed-meshheading:20145129-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20145129-Gene Regulatory Networks,
pubmed-meshheading:20145129-Genes, Developmental,
pubmed-meshheading:20145129-Homeodomain Proteins,
pubmed-meshheading:20145129-Humans,
pubmed-meshheading:20145129-Nerve Growth Factors,
pubmed-meshheading:20145129-Nuclear Receptor Coactivator 1,
pubmed-meshheading:20145129-Prognosis,
pubmed-meshheading:20145129-Protein Binding,
pubmed-meshheading:20145129-S100 Proteins,
pubmed-meshheading:20145129-Transcription Factors,
pubmed-meshheading:20145129-Tumor Cells, Cultured
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pubmed:year |
2010
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pubmed:articleTitle |
Interaction of developmental transcription factor HOXC11 with steroid receptor coactivator SRC-1 mediates resistance to endocrine therapy in breast cancer [corrected].
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pubmed:affiliation |
Endocrine Oncology Research, Department of Surgery, Royal College of Surgeons in Ireland, Dublin D2, Ireland.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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