Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer

Meng-Lay Lin, Hetal Patel, Judit Remenyi, Christopher R. S. Banerji, Chun-Fui Lai, Manikandan Periyasamy, Ylenia Lombardo, Claudia Busonero, Silvia Ottaviani, Alun Passey, Philip R. Quinlan, Colin A. Purdie, Lee B. Jordan, Alastair M. Thompson, Richard S. Finn, Oscar M. Rueda, Carlos Caldas, Jesus Gil, R. Charles Coombes, Frances V. Fuller-PaceAndrew E. Teschendorff, Laki Buluwela, Simak Ali

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)21685-21703
    Number of pages18
    JournalOncotarget
    Volume6
    Issue number25
    DOIs
    Publication statusPublished - 28 Aug 2015

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    Cite this

    Lin, M-L., Patel, H., Remenyi, J., Banerji, C. R. S., Lai, C-F., Periyasamy, M., Lombardo, Y., Busonero, C., Ottaviani, S., Passey, A., Quinlan, P. R., Purdie, C. A., Jordan, L. B., Thompson, A. M., Finn, R. S., Rueda, O. M., Caldas, C., Gil, J., Coombes, R. C., ... Ali, S. (2015). Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer. Oncotarget, 6(25), 21685-21703. https://doi.org/10.18632/oncotarget.3942