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The Effect of AR Overexpression on Androgen Signaling in Prostate Cancer

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Androgen-Responsive Genes in Prostate Cancer

Abstract

Androgen receptor (AR) signaling pathway is required for both development of normal prostate gland and prostate cancer (PC). Patient with advanced disease are usually treated with androgen deprivation therapy. However, this treatment is only palliative, since a castration-resistant PC (CRPC) usually arises within 2–3 years of treatment. The mechanism by which CRPC develops is yet to be fully understood. However, common alteration in CRPC is the overexpression of the AR. Several studies have addressed the molecular changes occurring in AR overexpressing PC cells. The overexpression of AR enhances the binding of the receptor to chromatin in the presence of low concentrations of androgens. Furthermore, under the same conditions, AR overexpression alters also the dynamics of chromatin binding of the receptor and the binding of basic components of the transcriptional machinery. These changes translate into global epigenetic changes, which deserve more attention. Many studies have found that AR activation in CRPC cell models stimulates a different transcriptional program, which may be influenced by cooperative functions of other transcription factors. Thus, not only a single target gene but also a network of genes could be responsible for the disease progression. In fact, functional studies have shown that androgen-regulated genes, which are over­expressed in CRPC, are also likely to be important in PC progression.

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Authors and Affiliations

  1. Institute of Biomedical Technology and BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland

    Alfonso Urbanucci, Kati K. Waltering & Tapio Visakorpi

  2. Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, Forksningsparken, University of Oslo, Oslo, Norway

    Alfonso Urbanucci & Ian G. Mills

  3. Department of Signal Processing and BioMediTech, Tampere University of Technology, Tampere, Finland

    Kati K. Waltering

  4. CRUK Cambridge Research Institute, Cambridge, UK

    Ian G. Mills

  5. Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway

    Ian G. Mills

  6. Department of Urology, Oslo University Hospital, Oslo, Norway

    Ian G. Mills

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  1. Alfonso Urbanucci
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  2. Kati K. Waltering
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  3. Ian G. Mills
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  4. Tapio Visakorpi
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Correspondence to Tapio Visakorpi .

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  1. , Shadyside Medical Center, University of Pittsburgh, Centre Ave 5200, Pittsburgh, 15232, Pennsylvania, USA

    Zhou Wang

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Urbanucci, A., Waltering, K.K., Mills, I.G., Visakorpi, T. (2013). The Effect of AR Overexpression on Androgen Signaling in Prostate Cancer. In: Wang, Z. (eds) Androgen-Responsive Genes in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6182-1_12

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