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Are androgen receptor variants a substitute for the full-length receptor?

Nature Reviews Urology volume 12, pages 137–144 (2015)Cite this article

Subjects

Key Points

  • Truncated androgen receptor splice variants (AR-Vs) can resist androgen deprivation therapy

  • AR-Vs have an important role in the progression of prostate cancer to castration-resistant prostate cancer

  • AR-Vs could mediate resistance to prostate cancer therapies

  • Considering cell-specific and AR-V-specific transcriptional programmes, the repertoire of AR-V target genes is likely to be highly complex and overlap with known androgen-regulated genes

Abstract

Androgen receptor splice variants (AR-Vs)—which are expressed in castration-resistant prostate cancer (CRPC) cell lines and clinical samples—lack the C-terminal ligand-binding domain and are constitutively active. AR-Vs are, therefore, resistant to traditional androgen deprivation therapy (ADT). AR-Vs are induced by several mechanisms, including ADT, and might contribute to the progression of CRPC and resistance to ADT. AR-Vs could represent a novel therapeutic target for prostate cancer, especially in CRPC.

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Figure 1: The AR gene locus, AR-FL and AR-Vs.
Figure 2: Hypothetical model of the regulation of gene expression by AR-FL and AR-Vs in prostate cancer cells.

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Author information

Authors and Affiliations

  1. Department of Urology, First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China

    Ji Lu

  2. Department of Urology, Mayo Clinic, 200 First Street SW Rochester, 55905, MN, USA

    Travis Van der Steen

  3. Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, 55905, MN, USA

    Donald J. Tindall

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  1. Ji Lu
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  2. Travis Van der Steen
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  3. Donald J. Tindall
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All authors contributed substantially to the discussion of content and to the review and editing of the article before submission. J.L. wrote the article.

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Correspondence to Donald J. Tindall.

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Lu, J., der Steen, T. & Tindall, D. Are androgen receptor variants a substitute for the full-length receptor?. Nat Rev Urol 12, 137–144 (2015). https://doi.org/10.1038/nrurol.2015.13

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