Abstract
Breast cancer is a heterogeneous disease and can be classified based on gene expression profiles that reflect distinct epithelial subtypes. We identify prostate-derived ETS factor (PDEF) as a mediator of mammary luminal epithelial lineage-specific gene expression and as a factor required for tumorigenesis in a subset of breast cancers. PDEF levels strongly correlate with estrogen receptor (ER)-positive luminal breast cancer, and PDEF transcription is inversely regulated by ER and GATA3. Furthermore, PDEF is essential for luminal breast cancer cell survival and is required in models of endocrine resistance. These results offer insights into the function of this ETS factor that are clinically relevant and may be of therapeutic value for patients with breast cancer treated with endocrine therapy.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Epithelial Cells / metabolism
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Female
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GATA3 Transcription Factor / metabolism
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GATA3 Transcription Factor / physiology
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Gene Expression Regulation, Neoplastic*
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Hepatocyte Nuclear Factor 3-alpha / metabolism
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Hepatocyte Nuclear Factor 3-alpha / physiology
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Humans
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MCF-7 Cells
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Prognosis
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Proto-Oncogene Proteins c-ets / genetics
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Proto-Oncogene Proteins c-ets / metabolism
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Proto-Oncogene Proteins c-ets / physiology*
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Receptors, Estrogen / genetics*
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Receptors, Estrogen / metabolism
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fas Receptor / genetics
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fas Receptor / metabolism
Substances
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FAS protein, human
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FOXA1 protein, human
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GATA3 Transcription Factor
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GATA3 protein, human
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Hepatocyte Nuclear Factor 3-alpha
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Proto-Oncogene Proteins c-ets
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Receptors, Estrogen
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SPDEF protein, human
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fas Receptor