Title |
Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer
|
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Published in |
Nature Communications, July 2013
|
DOI | 10.1038/ncomms3175 |
Pubmed ID | |
Authors |
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, Janne Lehtiö |
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. |
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Geographical breakdown
Country | Count | As % |
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France | 1 | 14% |
United Kingdom | 1 | 14% |
United States | 1 | 14% |
Mexico | 1 | 14% |
Unknown | 3 | 43% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 43% |
Practitioners (doctors, other healthcare professionals) | 2 | 29% |
Science communicators (journalists, bloggers, editors) | 1 | 14% |
Scientists | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Netherlands | 1 | 1% |
United States | 1 | 1% |
Ireland | 1 | 1% |
Unknown | 75 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 14 | 18% |
Student > Master | 12 | 15% |
Researcher | 10 | 13% |
Student > Bachelor | 9 | 12% |
Student > Postgraduate | 7 | 9% |
Other | 15 | 19% |
Unknown | 11 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 23 | 29% |
Biochemistry, Genetics and Molecular Biology | 18 | 23% |
Medicine and Dentistry | 8 | 10% |
Engineering | 4 | 5% |
Computer Science | 3 | 4% |
Other | 10 | 13% |
Unknown | 12 | 15% |