Abstract
The pro-metastatic protein anterior gradient-2 (AGR2) was previously demonstrated as a predictive factor of poor response to tamoxifen treatment. In this study we aimed to delineate the key signalling pathway that may contribute to regulation of AGR2 protein induction in order to identify novel targets to overcome tamoxifen resistance in tumour cells. Together, our data identify PDPK1-AKT as a pro-oncogenic signalling pathway that triggers AGR2 protein induction in response to tamoxifen and suggest that AKT inhibitors could be used as part of a therapeutic strategy to treat tamoxifen resistant, AGR2 over-expressing cancers.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Phosphoinositide-Dependent Protein Kinases
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Antineoplastic Agents, Hormonal / pharmacology
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Base Sequence
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Line, Tumor
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Female
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Humans
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MicroRNAs
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Molecular Sequence Data
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Mucoproteins
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Oncogene Proteins
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Protein Serine-Threonine Kinases / metabolism
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism*
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Ribonucleosides / pharmacology
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Serine / metabolism
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Signal Transduction / drug effects
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Tamoxifen / pharmacology
Substances
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AGR2 protein, human
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Antineoplastic Agents, Hormonal
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MicroRNAs
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Mucoproteins
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Oncogene Proteins
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Proteins
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Ribonucleosides
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Tamoxifen
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triciribine
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Serine
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3-Phosphoinositide-Dependent Protein Kinases
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PDPK1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt