Androgen receptor abnormalities in castration-recurrent prostate cancer.
Open accessAbstract
The androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Despite the success of androgen-deprivation therapy, remission occurs in almost all cases. This stage of the disease is called castration-recurrent PCa (CRPC). CRPC cells adapt to low circulating levels of androgens, and active AR is maintained by numerous cellular mechanisms. Some mutations in the AR make it more responsive to lower androgen levels or other steroids. Furthermore, in this advance stage of the disease, PCa cells express the enzymes necessary for de novo synthesis of androgens. AR is also activated in a ligand-independent manner. Therefore, it is important to understand the mechanisms of AR activation and its deregulation during CRPC. The purpose of this article is to discuss mechanisms that are involved in modulation of AR activity and specificity.
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The majority of androgen receptor variants described to date are characterized by loss of significant portions of the DNA-binding domain and ligand-binding domain, meaning they lose key motifs for ligand-dependent regulation and for degradation.
“As reviewed in Ref. 79, the majority of the variants described to date are characterized by the loss of significant portions of the DBD and LBD (C-terminal), which means that in addition to losing motifs for ligand-dependent regulation, they also lose key motifs for degradation.”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [79]
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Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer
Lamont, K. R., & Tindall, D. J. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0469 · Cited by 150 · see citing works
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- Authors
- Nacusi, L. P., & Tindall, D. J.
- Affiliations
- Mayo Clinic (US)
- Venue
- Expert Review of Endocrinology & Metabolism
- Publisher
- Informa UK Limited
- Published
- 2009-09
- Volume
- 4
- Issue
- 5
- Pages
- 417-422
- ISSN
- 1744-6651 (ISSN-L)
- 1744-8417
- PMC
- PMC2835169
- OpenAlex
- W2146314117
- Cited by
- 27
- References
- 68
- Citations by year
- 2025: 1 · 2021: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 4
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Review of Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA121277, R01CA125747, P50CA091956)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- androgen receptor, castration-resistant prostate cancer, androgen deprivation therapy, androgen receptor mutations, ligand-independent receptor activation
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