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Cited by 81Prostate Cancer Treatment and ResearchCancer, Hypoxia, and MetabolismEstrogen and related hormone effects

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Hypoxia Increases Androgen Receptor Activity in Prostate Cancer Cells

Park, Soo-Yeon, Kim, Yun-Jeong, Gao, Allen C., Mohler, James L., Onate, Sergio A., Hidalgo, Alejandro A., Ip, Clement, Park, Eun-Mi, Yoon, Sun Young, Park, Young-Mee·2006·Cancer Research
DOI 10.1158/0008-5472.can-05-1341
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Abstract

Recent studies show that prostate cancer cells are able to survive in a hypoxic tumor environment, and the extent of tumor hypoxia correlates with poor clinical outcome. Androgen deprivation, the most common form of prostate cancer therapy, was itself shown to induce a state of transient hypoxia at the microenvironmental level. Because androgen receptor (AR) signaling plays a critical role in prostate cancer, we investigated the effect of hypoxia in regulating AR function. We found that in LNCaP prostate cancer cells, AR binding to the androgen-responsive element (ARE), prostate-specific antigen accumulation, and ARE-reporter gene activity were increased after hypoxia treatment. Hypoxia-enhanced AR function was also observed when AR was exogenously introduced into AR-null DU145 cells. Confocal microscopy and chromatin immunoprecipitation assays showed that AR translocation to the nucleus and AR recruitment to the prostate-specific antigen promoter were facilitated after hypoxia treatment. The AR stimulatory effect seemed to be ligand-dependent because it was abrogated when cells were cultured in an androgen-depleted medium, but was restored with the addition of R1881, a synthetic androgen. The sensitivity of AR activation to R1881 was also increased after hypoxia treatment. Although concentrations of <1 nmol/L R1881 did not induce ARE reporter activity under normoxic conditions, exposure to hypoxia greatly potentiated the AR response to low levels of R1881. Collectively, our…

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Metadata

Authors
Park, S.-Y., Kim, Y.-J., Gao, A. C., Mohler, J. L., Onate, S. A., Hidalgo, A. A., Ip, C., Park, E.-M., Yoon, S. Y., & Park, Y.-M.
Affiliations
  • Roswell Park Comprehensive Cancer Center (US)
  • 3Urologic Oncology, and
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2006-05-15
Volume
66
Issue
10
Pages
5121-5129
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-05-1341
OpenAlex
W2109674742
Cited by
81
References
54
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 1 · 2013: 5 · 2012: 7
FWCI
5.30
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA 16056., R01CA111846, CA 09796, CA111846, P30CA016056)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords
hypoxia, androgen receptor, prostate cancer, androgen-responsive element, prostate-specific antigen, nuclear translocation, androgen deprivation therapy, R1881, treatment resistance, tumor hypoxia, hypoxia/reoxygenation
MeSH terms
Cell Nucleus, Humans, Male, Promoter Regions, Genetic, Prostatic Neoplasms, Receptors, Androgen, Transfection, Transcriptional Activation, Cell Hypoxia, Response Elements, Cell Line, Tumor

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