The HER2/Grb2/Akt pathway regulates the DNA binding activity of AP-1 in breast cancer cells.
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.
Mendoza-Gamboa
Edgar
E
Department of Bioimmunotherapy, Section of Immunobiology and Drug Carriers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Siwak
Doris R
DR
Tari
Ana M
AM
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D051380:GRB2 Adaptor Protein; D016758:Genes, jun / Q000502:physiology; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051380:GRB2 Adaptor Protein; D016376:Oligonucleotides, Antisense; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D018168:Receptors, Retinoic Acid; D018808:Transcription Factor AP-1; D014212:Tretinoin; C495948:GRB2 protein, human; C494918:AKT1 protein, human