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). AKR1C3, Aldo-keto reductase family 1 member C3, is a steroidogenic enzyme that plays a crucial role in the conversion of the adrenal androgen dehydroepiandrosterone (DHEA) into high affinity ligands for the androgen receptor (T and 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 up-regulated in CRPC tissue, compared to 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 TURP specimens. DuCaP, a CRPC cell line that has high AKR1C3 expression levels, was able to use and convert 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.
Written by:
Hamid AR, Pfeiffer MJ, Verhaegh GW, Schaafsma E, Brandt A, Sweep FC, Sedelaar JP, Schalken JA. Are you the author?
Dept. Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Dept. Urology, Ciptomangunkusumo Hospital, Dept. Surgery, Faculty of Medicine, University of Indonesia, Indonesia; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
Reference: Mol Med. 2012 Nov 26. doi: Epub ahead of print.
doi: 10.2119/molmed.2012.00296
PubMed Abstract
PMID: 23196782
