Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer
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Meng-Lay Lin1,*, Hetal Patel1,*, Judit Remenyi2, Christopher R. S. Banerji3,4, Chun-Fui Lai1, Manikandan Periyasamy1, Ylenia Lombardo1, Claudia Busonero1, Silvia Ottaviani1, Alun Passey1, Philip R. Quinlan5, Colin A. Purdie5, Lee B. Jordan5, Alastair M. Thompson6, Richard S. Finn7, Oscar M. Rueda8, Carlos Caldas8, Jesus Gil9, R. Charles Coombes1, Frances V. Fuller-Pace2, Andrew E. Teschendorff3,4, Laki Buluwela1, Simak Ali1
1Department of Surgery & Cancer, Imperial College London, London, UK
2Division of Cancer Research, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK
3Statistical Genomics Group, UCL Cancer Institute, University College London, London, UK
4Centre of Mathematics and Physics in Life & Experimental Sciences, University College London, UK
5Dundee Cancer Centre, Clinical Research Centre, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK
6Department of Surgical Oncology, MD Anderson Cancer Center, Houston, USA
7Geffen School of Medicine at UCLA, Los Angeles, CA USA
8Cancer Research UK Cambridge Institute, University of Cambridge Li Ka Shing Centre, Cambridge, UK
9Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London, UK
*These authors have contributed equally to this work
Simak Ali, e-mail: firstname.lastname@example.org
Keywords: cancer, nuclear receptors, expression profiling, breast cancer, tumour classification
Received: March 11, 2015 Accepted: April 30, 2015 Published: May 13, 2015
The Nuclear Receptor (NR) superfamily of transcription factors comprises 48 members, several of which have been implicated in breast cancer. Most important is estrogen receptor-α (ERα), which is a key therapeutic target. ERα action is facilitated by co-operativity with other NR and there is evidence that ERα function may be recapitulated by other NRs in ERα-negative breast cancer. In order to examine the inter-relationships between nuclear receptors, and to obtain evidence for previously unsuspected roles for any NRs, we undertook quantitative RT-PCR and bioinformatics analysis to examine their expression in breast cancer. While most NRs were expressed, bioinformatic analyses differentiated tumours into distinct prognostic groups that were validated by analyzing public microarray data sets. Although ERα and progesterone receptor were dominant in distinguishing prognostic groups, other NR strengthened these groups. Clustering analysis identified several family members with potential importance in breast cancer. Specifically, RORγ is identified as being co-expressed with ERα, whilst several NRs are preferentially expressed in ERα-negative disease, with TLX expression being prognostic in this subtype. Functional studies demonstrated the importance of TLX in regulating growth and invasion in ERα-negative breast cancer cells.
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