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

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 Helou, Kamilla Krawiec, Lena Kanter, Anders Hjerpe, Olle Stål, Barbro K. Linderholm and Janne Lehtiö ()
Additional contact information
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
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
Janne Lehtiö: Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institute

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3175

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