Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer.
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.
Department of Surgery & Cancer, Imperial College London, London, UK.
Meng-Lay
ML
Lin
Department of Surgery & Cancer, Imperial College London, London, UK.
Hetal
H
Patel
Division of Cancer Research, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
Judit
J
Remenyi
Statistical Genomics Group, UCL Cancer Institute, University College London, London, UK.|Centre of Mathematics and Physics in Life & Experimental Sciences, University College London, London, UK.
Christopher R S
CR
Banerji
Department of Surgery & Cancer, Imperial College London, London, UK.
Chun-Fui
CF
Lai
Department of Surgery & Cancer, Imperial College London, London, UK.
Manikandan
M
Periyasamy
Department of Surgery & Cancer, Imperial College London, London, UK.
Ylenia
Y
Lombardo
Department of Surgery & Cancer, Imperial College London, London, UK.
Claudia
C
Busonero
Department of Surgery & Cancer, Imperial College London, London, UK.
Silvia
S
Ottaviani
Department of Surgery & Cancer, Imperial College London, London, UK.
Alun
A
Passey
Dundee Cancer Centre, Clinical Research Centre, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
Philip R
PR
Quinlan
Dundee Cancer Centre, Clinical Research Centre, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
Colin A
CA
Purdie
Dundee Cancer Centre, Clinical Research Centre, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
Lee B
LB
Jordan
Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
Alastair M
AM
Thompson
Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Richard S
RS
Finn
Cancer Research UK Cambridge Institute, University of Cambridge Li Ka Shing Centre, Cambridge, UK.
Oscar M
OM
Rueda
Cancer Research UK Cambridge Institute, University of Cambridge Li Ka Shing Centre, Cambridge, UK.
Carlos
C
Caldas
Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London, UK.
Jesus
J
Gil
Department of Surgery & Cancer, Imperial College London, London, UK.
R Charles
RC
Coombes
Division of Cancer Research, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
Frances V
FV
Fuller-Pace
Statistical Genomics Group, UCL Cancer Institute, University College London, London, UK.|Centre of Mathematics and Physics in Life & Experimental Sciences, University College London, London, UK.
Andrew E
AE
Teschendorff
Department of Surgery & Cancer, Imperial College London, London, UK.
Laki
L
Buluwela
Department of Surgery & Cancer, Imperial College London, London, UK.
Simak
S
Ali
D001943:Breast Neoplasms / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016000:Cluster Analysis; D019295:Computational Biology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors; D011379:Prognosis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism*
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C088601:NR2E1 protein, human; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear
breast cancer; cancer; expression profiling; nuclear receptors; tumour classification