Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Sep 1;7(9):a030452.
doi: 10.1101/cshperspect.a030452.

Androgen Signaling in Prostate Cancer

Charles Dai  1   2 , Hannelore Heemers  1   2   3   4 , Nima Sharifi  1   2   3   4
Affiliations
Review

Androgen Signaling in Prostate Cancer

Charles Dai et al. Cold Spring Harb Perspect Med. .

Abstract

The androgen-signaling axis plays a pivotal role in the pathogenesis of prostate cancer. Since the landmark discovery by Huggins and Hodges, gonadal depletion of androgens has remained a mainstay of therapy for advanced disease. However, progression to castration-resistant prostate cancer (CRPC) typically follows and is largely the result of restored androgen signaling. Efforts to understand the mechanisms behind CRPC have revealed new insights into dysregulated androgen signaling and intratumoral androgen synthesis, which has ultimately led to the development of several novel androgen receptor (AR)-directed therapies for CRPC. However, emergence of resistance to these newer agents has also galvanized new directions in investigations of prereceptor and postreceptor AR regulation. Here, we review our current understanding of AR signaling as it pertains to the biology and natural history of prostate cancer.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Pathways of androgen biosynthesis in normal physiology and prostate cancer. Key enzymes are denoted next to arrows for each reaction. Specific isoenzymes responsible for particular reactions are discussed in the main text. DHEA, dehydroepiandrosterone; AD, androstenedione; T, testosterone; DHT, dihydrotestosterone.
Figure 2.
Figure 2.
The androgen receptor (AR) gene locus and structure of the AR (full-length and AR-V7). The transcript for wild-type AR full-length (FL) includes eight exons, which correspond to the four respective domains of the AR protein (as depicted by color scheme). AR-V7 includes a cryptic exon region (CE3b) at the carboxyl terminus. NTD, Amino-terminal domain; DBD, DNA-binding domain; LBD, ligand-binding domain; NLS, nuclear localization signal.
Figure 3.
Figure 3.
Prereceptor and receptor-level modulation of androgen receptor (AR) action within the prostate cancer cell. Examples of transcriptional coregulators discussed within the text are depicted but are a limited representation of all potential participating proteins. DHEA, dehydroepiandrosterone; SHBG, sex hormone–binding globulin; T, testosterone; DHT, dihydrotestosterone; HSP, heat shock protein; TF, transcription factor; ARE, androgen response element.
See this image and copyright information in PMC

References

    1. Adeniji AO, Chen M, Penning TM. 2013. AKR1C3 as a target in castrate resistant prostate cancer. J Steroid Biochem Mol Biol 137: 136–149. - PMC - PubMed
    1. Agoulnik IU, Weigel NL. 2009. Coactivator selective regulation of androgen receptor activity. Steroids 74: 669–674. - PMC - PubMed
    1. An J, Wang C, Deng Y, Yu L, Huang H. 2014. Destruction of full-length androgen receptor by wild-type SPOP, but not prostate-cancer-associated mutants. Cell Rep 6: 657–669. - PMC - PubMed
    1. Andersson S, Berman DM, Jenkins EP, Russell DW. 1991. Deletion of steroid 5 α-reductase 2 gene in male pseudohermaphroditism. Nature 354: 159–161. - PMC - PubMed
    1. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, et al. 2014. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371: 1028–1038. - PMC - PubMed