In vivo amplification of the androgen receptor gene and progression of human prostate cancer
Abstract
Overexpression of amplified genes is often associated with the acquisition of resistance to cancer therapeutic agents in vitro. We have identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene. Comparative genomic hybridization shows that amplification of the Xq11-q13 region (the location), is common in tumours recurring during androgen deprivation therapy. We found high-level AR amplification in seven of 23 (30%) recurrent tumours, but in none of the specimens taken from the same patients prior to therapy. Our results suggest that AR amplification emerges during androgen deprivation therapy by facilitating tumour cell growth in low androgen concentrations.
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Mechanisms of ARSI resistance include AR gene amplification, AR enhancer amplification, AR mutation, AR genomic structural rearrangements, AR splice variants and polymorphisms in androgen metabolism genes.
“These mechanisms of resistance include AR gene amplification22,23, AR enhancer amplification2,24,25, AR mutation26, AR genomic structural rearrangements27, AR splice variants28 and polymorphisms in androgen metabolism genes29.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [22]
Tumor alterations that reactivate AR signaling during treatment with an ARSI have been identified.
“We and other groups have identified tumor alterations that reactivate AR signaling during treatment with an ARSI2,22–29.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [22]
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“We and other groups have identified tumor alterations that reactivate AR signaling during treatment with an ARSI 2,22–29 .”
- Authors
- Visakorpi, T., Hyytinen, E., Koivisto, P., Tanner, M., Keinänen, R., Palmberg, C., Palotie, A., Tammela, T., Isola, J., & Kallioniemi, O.-P.
- Affiliations
- Tampere University Hospital (FI)
- Tampere University (FI)
- Helsinki University Hospital (FI)
- Venue
- Nature Genetics
- Published
- 1995-04
- Volume
- 9
- Issue
- 4
- Pages
- 401-406
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2022635468
- Cited by
- 1,484
- References
- 32
- Citations by year
- 2026: 16 · 2025: 28 · 2024: 21 · 2023: 51 · 2022: 39 · 2021: 55 · 2020: 33 · 2019: 46 · 2018: 49 · 2017: 62 · 2016: 69 · 2015: 69 · 2014: 72 · 2013: 77 · 2012: 59
- FWCI
- 36.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Keywords
- prostate cancer, androgen deprivation therapy, tumor recurrence, tumor progression
- MeSH terms
- Aged, Drug Resistance, Gene Amplification, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Prostatic Neoplasms, Receptors, Androgen, X Chromosome, In Situ Hybridization, Fluorescence
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