Abstract
We showed that the HER2/Grb2/Akt pathway induces all-trans retinoic acid (ATRA) resistance in breast cancer cells by suppressing the DNA binding activity of retinoic acid receptors (RAR). AP-1 activation was shown to induce ATRA resistance. Here, we determined whether AP-1 binding activity is correlated with ATRA resistance in HER2-overexpressing cells. Inhibition of HER2/Grb2/Akt decreased AP-1 binding activity in HER2-transfected cells, but increased AP-1 activity in cells that are naturally HER2-overexpressing. Since HER2/Grb2/Akt inhibition sensitized both cell types to ATRA, our results indicate that, unlike RAR, AP-1 binding activity is not correlated with ATRA sensitivity in HER2-overexpressing breast cancer cells.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / antagonists & inhibitors
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Antineoplastic Agents / therapeutic use
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Electrophoretic Mobility Shift Assay
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Female
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GRB2 Adaptor Protein
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Genes, jun / physiology
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Humans
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Oligonucleotides, Antisense / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Receptor, ErbB-2 / antagonists & inhibitors
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Receptor, ErbB-2 / metabolism*
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Receptors, Retinoic Acid / metabolism
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Transcription Factor AP-1 / genetics*
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Transcription Factor AP-1 / metabolism
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Tretinoin / therapeutic use
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Tumor Cells, Cultured
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src Homology Domains
Substances
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Adaptor Proteins, Signal Transducing
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Antineoplastic Agents
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GRB2 Adaptor Protein
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GRB2 protein, human
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Oligonucleotides, Antisense
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Proto-Oncogene Proteins
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Receptors, Retinoic Acid
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Transcription Factor AP-1
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Tretinoin
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Protein-Tyrosine Kinases
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Receptor, ErbB-2
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt