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Maintaining and reprogramming genomic androgen receptor activity in prostate cancer

Nature Reviews Cancer volume 14, pages 187–198 (2014)Cite this article

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A Corrigendum to this article was published on 20 March 2014

This article has been updated

Abstract

Prostate cancer treatment is dominated by strategies to control androgen receptor (AR) activity. AR has an impact on prostate cancer development through the regulation of not only transcription networks but also genomic stability and DNA repair, as manifest in the emergence of gene fusions. Whole-genome maps of AR binding sites and transcript profiling have shown changes in the recruitment and regulatory effect of AR on transcription as prostate cancer progresses. Defining other factors that are involved in this reprogramming of AR function gives various opportunities for cancer detection and therapeutic intervention.

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Figure 1: Androgen receptor activity reflects autocrine and paracrine signalling, copy number amplification and signalling crosstalk.
Figure 2: Interactions between androgen receptor and other transcription factors change androgen receptor recruitment to DNA, as well as the expression and sets of genes associated with biological pathways.
Figure 3: Chromatin readers and modifying enzymes alter the chromatin landscape to change androgen receptor binding to DNA.
Figure 4: Defining the sequence of androgen receptor reprogramming events alongside clinical prostate cancer progression is now the challenge and will further advance personalized medicine.

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  • 20 March 2014

    In the original version of this article, several references were incorrect. References 13, 29, 34, 41, 88, 89, 90 and 91 were incorrect and have now been replaced with the correct citations. In addition, reference 59 was incorrectly cited in the first sentence of the "Speckle-type POZ protein (SPOP)" subsection at the top of page 195, and this has now been removed. All of these corrections have been made online.

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Acknowledgements

The author would like to thank members of the Mills laboratory for their critical reading of the manuscript. The manuscript has evolved from discussions with many close colleagues within the field, particularly D. Neal, N. Sharma, C. Massie, H. Itkonen, S. Barfeld, A. Urbanucci, P. Rennie and G. Coetzee, and many more. Research within the Mills laboratory is funded by the Movember Foundation, the US National Institutes of Health, Helse Sør-Øst, Norway, the Norwegian Research Council, the Norwegian Cancer Society, the Finnish Cultural Society and the European Union. The author would like to apologize to all colleagues whose work he was unable to cite in this Opinion article.

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  1. Norway; the Departments of Cancer Prevention and Urology, Prostate Cancer Research Group, Centre for Molecular Medicine Norway (NCMM), University of Oslo and Oslo University Hospitals, N-0318 Oslo, Institute of Cancer Research and Oslo University Hospitals, N-0424 Oslo, Norway; and the Uro-Oncology Research Group, Cambridge Research Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.,

    Ian G. Mills

  2. the Departments of Cancer Prevention and Urology, Institute of Cancer Research and Oslo University Hospitals, N-0424 Oslo, Norway,

    Ian G. Mills

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Mills, I. Maintaining and reprogramming genomic androgen receptor activity in prostate cancer. Nat Rev Cancer 14, 187–198 (2014). https://doi.org/10.1038/nrc3678

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