The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.
AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase): Roles in malignancy and endocrine disorders
Open accessAbstract
Aldo-Keto-Reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase (HSD)/prostaglandin (PG) F 2α synthase) is the only 17β-HSD that is not a short-chain dehydrogenase/reductase. By acting as a 17-ketosteroid reductase, AKR1C3 produces potent androgens in peripheral tissues which activate the androgen receptor (AR) or act as substrates for aromatase. AKR1C3 is implicated in the production of androgens in castration-resistant prostate cancer (CRPC) and polycystic ovarian syndrome; and is implicated in the production of aromatase substrates in breast cancer. By acting as an 11-ketoprostaglandin reductase, AKR1C3 generates 11β-PGF 2α to activate the FP receptor and deprives peroxisome proliferator activator receptorγ of its putative PGJ 2 ligands. These growth stimulatory signals implicate AKR1C3 in non-hormonal dependent malignancies e.g. acute myeloid leukemia (AML). AKR1C3 moonlights by acting as a co-activator of the AR and stabilizes ubiquitin ligases. AKR1C3 inhibitors have been used clinically for CRPC and AML and can be used to probe its pluripotency.
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“other prostaglandin synthases in the same family as PTGES3 have been implicated in the production of androgens48,49.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [48]
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“PTGES3 protein is reported to have several protein functions and to be localized to both the cytosol and nucleus41–49 (Fig. 3f).”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [48]
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Citations
Cites
Abiraterone and Increased Survival in Metastatic Prostate Cancer
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9-cis retinoic acid is a high affinity ligand for the retinoid X receptor
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“As 9-cis-retinoic acid is the major ligand for RXR (Heyman et al., 1992; Levin et al., 1992), the conversion of 9cis-retinal to 9-cis-retinol mediated by AKR1B15 would deprive RXR of its 9-cis-retinoic acid ligand.”
BackgroundInfluential9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα
Levin, A. A., Sturzenbecker, L. J., Kazmer, S., Bosakowski, T., Huselton, C. A., Allenby, G., Speck, J., ratzeisen, C., Rosenberger, M., Lovey, A. J., et al. (1992) · Nature · doi:10.1038/355359a0 · Cited by 1,221
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Self-citationAntitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study
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Self-citationPENNING, T. M., BURCZYNSKI, M. E., JEZ, J. M., HUNG, C.-F., LIN, H.-K., MA, H., MOORE, M., PALACKAL, N., & RATNAM, K. (2000) · Biochemical Journal · doi:10.1042/bj3510067 · Cited by 649
Self-citationComparative anatomy of the aldo–keto reductase superfamily
Jez, J. M., BENNETT, M. J., Schlegel, B. P., Lewis, M., & Penning, T. M. (1997) · Biochemical Journal · doi:10.1042/bj3260625 · Cited by 603
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Research works printed but not linked: 1
- Rizal, 2012, Aldo-keto reductase 1 member C3 (AKR1C3) is a biomarker and therapeutic target for castration-resistant prostate cancer, Mol. Med., 18, 1449, 10.2119/molmed.2012.00296 · DOI
Cited by
Sorted by citations
Targeting the Androgen Signaling Axis in Prostate Cancer
Dai, C. S., Dehm, S. M., & Sharifi, N. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.23.00433 · Cited by 182
Aldo-Keto Reductases and Cancer Drug Resistance
Penning, T. M., Jonnalagadda, S. K., Trippier, P. C., & Rižner, T. L. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000122 · Cited by 158
Self-citationThe Role of Prostaglandins in Different Types of Cancer
Jara-Gutiérrez, Á., & Baladrón, V. (2021) · Cells · doi:10.3390/cells10061487 · Cited by 111
Overview of AKR1C3: Inhibitor Achievements and Disease Insights
Liu, Y., He, S., Chen, Y., Liu, Y., Feng, F., Liu, W., Guo, Q., Zhao, L., & Sun, H. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b02138 · Cited by 105
Paulukinas, R. D., Mesaros, C., & Penning, T. M. (2022) · Endocrinology · doi:10.1210/endocr/bqac068 · Cited by 63
Self-citation
Metadata
- Authors
- Penning, T. M.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Penning, Trevor M.
- ORCID
- Penning, Trevor M.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 489
- Pages
- 82-91
- ISSN
- 0303-7207 (ISSN-L)
- PMC
- PMC6422768
- OpenAlex
- W2890789239
- Cited by
- 117
- References
- 99
- Citations by year
- 2026: 18 · 2025: 13 · 2024: 20 · 2023: 14 · 2022: 20 · 2021: 17 · 2020: 11 · 2019: 4
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P30-ES013508, R01-CA90744)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- AKR1C3, 17β-hydroxysteroid dehydrogenase type 5, androgen production, castration-resistant prostate cancer, polycystic ovary syndrome, breast cancer, prostaglandin F2alpha, FP receptor, PPARγ, acute myeloid leukemia, AKR1C3 inhibitors, moonlighting enzymes
- MeSH terms
- Aldo-Keto Reductase Family 1 Member C3, Endocrine System Diseases, Endocrine Gland Neoplasms, Enzyme Inhibitors, Humans, Steroids, Epigenesis, Genetic
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