Abstract
HER2-overexpressing breast cancers are characterized by frequent distant metastasis and often develop resistance after short-term effective treatment with the monoclonal antibody drug, trastuzumab. Here, we found that the oncogenic miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted metastasis of HER2-positive breast cancers. The tumor suppressor PTEN was identified as a miR-221 target; overexpression of PTEN abrogated the aforementioned miR-221-induced malignant phenotypes of the cells. These findings indicate that miR-221 may promote trastuzumab resistance and metastasis of HER2-positive breast cancers by targeting PTEN, suggesting its role as a potential biomarker for progression and poor prognosis, and as a novel target for trastuzumab-combined treatment of breast cancers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal, Humanized / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / therapy*
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Cell Line, Tumor
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Drug Resistance, Neoplasm / genetics
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Female
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Humans
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Neoplasm Invasiveness / genetics
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Neoplasm Metastasis / genetics
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PTEN Phosphohydrolase / antagonists & inhibitors
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PTEN Phosphohydrolase / genetics*
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RNA, Neoplasm / genetics
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RNA, Neoplasm / metabolism
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / metabolism*
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Trastuzumab
Substances
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Biomarkers, Tumor
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MIRN221 microRNA, human
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MicroRNAs
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RNA, Neoplasm
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ERBB2 protein, human
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Receptor, ErbB-2
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PTEN Phosphohydrolase
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PTEN protein, human
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Trastuzumab