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Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer

Author

Listed:
  • Henrik J. Johansson

    (Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institute)

  • Betzabe C. Sanchez

    (Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institute)

  • Filip Mundt

    (Karolinska Institute)

  • Jenny Forshed

    (Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institute)

  • Aniko Kovacs

    (Sahlgrenska Academy, University Hospital)

  • Elena Panizza

    (Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institute)

  • Lina Hultin-Rosenberg

    (Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institute)

  • Bo Lundgren

    (Deptartment of Genetics, Microbiology and Toxicology, Cell Screening Facility, SciLifeLab Stockholm, Stockholm University)

  • Ulf Martens

    (Deptartment of Genetics, Microbiology and Toxicology, Cell Screening Facility, SciLifeLab Stockholm, Stockholm University)

  • Gyöngyvér Máthé

    (Sahlgrenska Academy, University Hospital)

  • Zohar Yakhini

    (Agilent Laboratories
    Technion–Israel Institute of Technology)

  • Khalil Helou

    (Sahlgrenska Academy, University Hospital)

  • Kamilla Krawiec

    (Regional Oncology Centre, Karolinska University Hospital)

  • Lena Kanter

    (Karolinska Institute)

  • Anders Hjerpe

    (Karolinska Institute)

  • Olle Stål

    (Faculty of Health Sciences, Linköping University)

  • Barbro K. Linderholm

    (Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institute
    Sahlgrenska Academy, University Hospital)

  • Janne Lehtiö

    (Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institute)

Abstract

About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.

Suggested Citation

  • Henrik J. Johansson & Betzabe C. Sanchez & Filip Mundt & Jenny Forshed & Aniko Kovacs & Elena Panizza & Lina Hultin-Rosenberg & Bo Lundgren & Ulf Martens & Gyöngyvér Máthé & Zohar Yakhini & Khalil Hel, 2013. "Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer," Nature Communications, Nature, vol. 4(1), pages 1-10, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3175
    DOI: 10.1038/ncomms3175
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