Increased expression of type 2 3α-hydroxysteroid dehydrogenase/type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma
Abstract
Type 2 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) is a multi-functional enzyme that possesses 3alpha-, 17beta- and 20alpha-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3alpha-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of Delta(4)-androstene-3,17-dione to testosterone, 5alpha-dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), and 3alpha-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells.
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AKR1C3 is overexpressed in prostate cancer, presumably promoting cancer progression by increasing intratumoral androgen levels.
“AKR1C3 is also overexpressed in prostate cancer, presumably promoting cancer progression by increasing intratumoral androgen levels (Adeniji et al., 2013, Fung et al., 2006).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Fung et al., 2006
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- Authors
- Fung, K.-M., Samara, E. N. S., Wong, C., Metwalli, A., Krlin, R., Bane, B., Liu, C. Z., Yang, J. T., Pitha, J. V., Culkin, D. J., Kropp, B. P., Penning, T. M., & Lin, H.-K.
- Affiliations
- Oklahoma City VA Medical Center (US)
- University of Oklahoma Health Sciences Center (US)
- 1Department of Urology, University of Oklahoma Health Sciences Center, 920 Stanton L Young Blvd, WP3150, Oklahoma City, Oklahoma 73104, USA
- 2Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
- University of Pennsylvania (US)
- Venue
- Endocrine Related Cancer
- Publisher
- Bioscientifica
- Published
- 2006-03-01
- Volume
- 13
- Issue
- 1
- Pages
- 169-180
- ISSN
- 1351-0088 (ISSN-L)
- 1479-6821
- OpenAlex
- W2136750233
- Cited by
- 129
- References
- 40
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2019: 4 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 14 · 2013: 11 · 2012: 12
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Related Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA 97044)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK54925, DK-47015, R01DK054925, R01DK047015)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
- Keywords
- 3α-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, androgen receptor, prostate cancer, aldo-keto reductase, androgen metabolism, monoclonal antibodies, prostate epithelial cells, LNCaP cells, urothelial metaplasia, prostatitis, prostate atrophy
- MeSH terms
- Aldo-Keto Reductase Family 1 Member C3, Adenocarcinoma, Aged, Antibodies, Monoclonal, Epithelial Cells, Humans, Hydroxyprostaglandin Dehydrogenases, Immunoenzyme Techniques, Male, Middle Aged, Prostate, Prostatic Neoplasms, Receptors, Androgen, Tumor Cells, Cultured, 3-Hydroxysteroid Dehydrogenases, Blotting, Western, Gene Expression Regulation, Enzymologic, Stromal Cells, Reverse Transcriptase Polymerase Chain Reaction
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