Abstract
Breast cancers are sensitive to hormones such as estrogen, which binds to and activates estrogen receptors (ER) leading to significant changes in gene expression. microRNAs (miRNA) have emerged as a major player in gene regulation, thus identification of miRNAs associated with normal or disrupted estrogen signaling is critical to enhancing our understanding of the diagnosis and prognosis of breast cancer. We have previously shown that 17β-estradiol (E2) induced activation of ERα in T47D cells results in significant changes in the expression of protein-coding genes involved in cell cycle, proliferation, and apoptosis. To identify miRNAs regulated by E2-activated ERα, we analysed their expression in T47D cells following E2-activation using both dual-color microarrays and TaqMan Low Density Arrays, and validations were carried out by real-time PCR. Although estrogen treatment results in altered expression of up to 900 protein-coding transcripts, no significant changes in mature miRNA expression levels could be confirmed. Whereas previous studies aiming to elucidate the role of miRNA in ER-positive breast cancers cell lines have yielded conflicting results, the work presented here represents a thorough investigation of and significant step forward in our understanding of ERα mediated miRNA regulation.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Validation Study
MeSH terms
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Breast Neoplasms / metabolism*
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Cell Line, Tumor
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Computational Biology / methods
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Estradiol / metabolism*
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Estrogen Receptor alpha / agonists*
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Estrogen Receptor alpha / metabolism
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Female
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Humans
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Kinetics
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Neoplasm Proteins / agonists
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Neoplasm Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Potassium Channels, Tandem Pore Domain / genetics
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Potassium Channels, Tandem Pore Domain / metabolism
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Proteinase Inhibitory Proteins, Secretory / genetics
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Proteinase Inhibitory Proteins, Secretory / metabolism
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RNA, Messenger / metabolism
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Real-Time Polymerase Chain Reaction
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Reproducibility of Results
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Serine Peptidase Inhibitors, Kazal Type
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Serine Proteinase Inhibitors / genetics
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Serine Proteinase Inhibitors / metabolism
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Trefoil Factor-1
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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ESR1 protein, human
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Estrogen Receptor alpha
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KCNK5 protein, human
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MicroRNAs
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Neoplasm Proteins
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Potassium Channels, Tandem Pore Domain
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Protein Isoforms
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Proteinase Inhibitory Proteins, Secretory
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RNA, Messenger
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SPINK4 protein, human
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Serine Peptidase Inhibitors, Kazal Type
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Serine Proteinase Inhibitors
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TFF1 protein, human
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Trefoil Factor-1
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Tumor Suppressor Proteins
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Estradiol