Aldo-keto reductase family 1 member C3 (AKR1C3) is a biomarker and therapeutic target for castration-resistant prostate cancer
SourceMolecular Medicine, 18, (2013), pp. 1449-55
Article / Letter to editor
Display more detailsDisplay less details
Laboratory of Genetic, Endocrine and Metabolic Diseases
SubjectIGMD 6: Hormonal regulation ONCOL 5: Aetiology, screening and detection; NCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 3: Translational research; ONCOL 3: Translational research NCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 5: Aetiology, screening and detection
Current endocrine treatment for advanced prostate cancer does not result in a complete ablation of adrenal androgens. Adrenal androgens can be metabolized by prostate cancer cells, which is one of the mechanisms associated with progression to castration-resistant prostate cancer (CRPC). Aldo-keto reductase family 1 member C3 (AKR1C3) is a steroidogenic enzyme that plays a crucial role in the conversion of adrenal androgen dehydroepiandrosterone (DHEA) into high-affinity ligands for the androgen receptor (testosterone [T] and dihydrotestosterone [DHT]). The aim of this study was to examine whether AKR1C3 could be used as a marker and therapeutic target for CRPC. AKR1C3 mRNA and protein levels were upregulated in CRPC tissue, compared with benign prostate and primary prostate cancer tissue. High AKR1C3 levels were found only in a subset of CRPC patients. AKR1C3 can be used as a biomarker for active intratumoral steroidogenesis and can be measured in biopsy or transurethral resection of the prostate specimens. DuCaP (a CRPC cell line that has high AKR1C3 expression levels) used and converted DHEA under hormone-depleted conditions into T and DHT. The DHEA-induced growth of DuCaP could be antagonized by indomethacine, an inhibitor of AKR1C3. This study indicates that AKR1C3 can be considered a therapeutic target in a subgroup of patients with high AKR1C3 expression.
This item appears in the following Collection(s)
- Academic publications 
- Electronic publications 
- Faculty of Medical Sciences 
- Open Access publications 
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.