Abstract
Acquisition of gemcitabine resistance in breast cancer has not been fully clarified. Prior studies suggest that miRNAs are important to chemoresistance in solid tumors and we confirmed that miR-21 is involved in the development of gemcitabine resistance. Epithelial-to-mesenchymal transition (EMT) and AKT pathway activation were noted to be important to this resistance as well. PTEN, a direct target gene of miR-21, was significantly downregulated in gemcitabine-resistant breast cancer cells and restoration of PTEN expression blocked miR-21-induced EMT and gemcitabine resistance. Our data offer novel insight into gemcitabine resistance in breast cancer and suggest that miR-21 may be used to predict optimal breast cancer therapy and may be a potential therapeutic target for reversing gemcitabine resistance.
Keywords:
Breast cancer; Epithelial to mesenchymal transition (EMT); Gemcitabine resistance; miR-21.
MeSH terms
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Animals
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Antimetabolites, Antineoplastic / pharmacology*
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Antimetabolites, Antineoplastic / therapeutic use
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Breast Neoplasms / drug therapy
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Breast Neoplasms / pathology*
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Cell Line, Tumor
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Cell Movement
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / pharmacology
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Deoxycytidine / therapeutic use
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Down-Regulation / genetics
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Drug Resistance, Neoplasm / genetics*
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Epithelial-Mesenchymal Transition / genetics*
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Female
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Gemcitabine
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Gene Expression Regulation, Neoplastic
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Humans
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MCF-7 Cells
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / metabolism*
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PTEN Phosphohydrolase / physiology
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Proto-Oncogene Proteins c-akt / physiology
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RNA, Neoplasm
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RNA, Small Interfering / genetics
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Signal Transduction
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Xenograft Model Antitumor Assays
Substances
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Antimetabolites, Antineoplastic
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MIRN21 microRNA, human
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MicroRNAs
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RNA, Neoplasm
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RNA, Small Interfering
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Deoxycytidine
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AKT1 protein, human
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Proto-Oncogene Proteins c-akt
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PTEN Phosphohydrolase
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PTEN protein, human
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Gemcitabine