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Cited by 267Prostate Cancer Treatment and ResearchCancer, Lipids, and MetabolismSperm and Testicular Function

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

Novel 5α‐steroid reductase (SRD5A3, type‐3) is overexpressed in hormone‐refractory prostate cancer

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Uemura, Motohide, Tamura, Kenji, Chung, Suyoun, Honma, Seijiro, Okuyama, Akihiko, Nakamura, Yusuke, Nakagawa, Hidewaki·2008·Cancer Science
DOI 10.1111/j.1349-7006.2007.00656.xPMC PMC11158902
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Abstract

Prostate cancer often relapses during androgen-depletion therapy, even under conditions in which a drastic reduction of circulating androgens is observed. There is some evidence that androgens remain present in the tissues of hormone-refractory prostate cancers (HRPC), and enzymes involved in the androgen and steroid metabolic pathway are likely to be active in HRPC cells. We previously carried out a genome-wide gene expression profile analysis of clinical HRPC cells by means of cDNA microarrays in combination with microdissection of cancer cells and found dozens of transactivated genes. Among them, we here report the identification of a novel gene, SRD5A2L, encoding a putative 5 alpha-steroid reductase that produces the most potent androgen, 5 alpha-dihydrotestosterone (DHT), from testosterone. Liquid chromatography-tandem mass spectrometry analysis following an in vitro 5 alpha-steroid reductase reaction validated its ability to produce DHT from testosterone, similar to type 1 5 alpha-steroid reductase. Because two types of 5 alpha-steroid reductase were previously reported, we termed this novel 5 alpha-steroid reductase 'type 3 5 alpha-steroid reductase' (SRD5A3). Reverse transcription-polymerase chain reaction and northern blot analyses confirmed its overexpression in HRPC cells, and indicated no or little expression in normal adult organs. Knockdown of SRD5A3 expression by small interfering RNA in prostate cancer cells resulted in a significant decrease in DHT production and a drastic reduction in cell viability. These findings indicate that a novel type 3 5 alpha-steroid reductase, SRD5A3, is associated with DHT production and maintenance of androgen-androgen receptor-pathway activation in HRPC cells, and that this enzymatic activity should be a promising molecular target for prostate cancer therapy.

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Metadata

Authors
Uemura, M., Tamura, K., Chung, S., Honma, S., Okuyama, A., Nakamura, Y., & Nakagawa, H.
Affiliations
Institute of Medical Science, The University of Tokyo (JP)
Corresponding author
Nakagawa, Hidewaki
ORCID
Venue
Cancer Science
Publisher
Wiley
Published
2007-11-06
Volume
99
Issue
1
Pages
81-86
ISSN
  • 1347-9032 (ISSN-L)
  • 1349-7006
DOI
10.1111/j.1349-7006.2007.00656.x
PMC
PMC11158902
OpenAlex
W2029877275
Cited by
263
References
29
Citations by year
2026: 5 · 2025: 12 · 2024: 13 · 2023: 11 · 2022: 12 · 2021: 8 · 2020: 9 · 2019: 13 · 2018: 15 · 2017: 14 · 2016: 16 · 2015: 12 · 2014: 18 · 2013: 21 · 2012: 21
FWCI
11.52
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Cancer Science (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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, Lipids, and Metabolism
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
SRD5A3, castration-resistant prostate cancer, dihydrotestosterone, androgen production, androgen receptor signaling, gene overexpression, siRNA knockdown
MeSH terms
Animals, Chlorocebus aethiops, Humans, Male, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, Dihydrotestosterone, Testosterone, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Transfection, COS Cells, RNA, Small Interfering, Cell Line, Tumor, Cell Growth Processes

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