Author/Editor		Lanišnik-Rižner, Tea; Lin, Hsueh K; Penning, Trevor M
Title		Role of human type 3 3alpha-hydroxysteroid dehydrogenase (AKR1C2) in androgen metabolism of prostate cancer cells
Type		članek
Source		Chem Biol Interact
Vol. and No.		, št. 143-144
Publication year		2003
Volume		str. 401-9
Language		eng
Abstract		Four human aldo-keto reductases (AKRs) that belong to the AKR1C subfamily function in vitro as 3-keto-, 17keto- and 20-ketosteroid reductases or as 3alpha-, 17/beta- and 20alpha- hydroxysteroid oxidases to varying degrees. By acting as ketosteroid reductases or hydroxysteroid oxidases these AKRs can either convert potent sex hormones (androgens, estrogens and progestins) into their inactive metabolites or they can form potent hormones by catalyzing the reverse reaction. In this manner they may regulate occupancy and trans-activation of steroid hormone receptors. Tissue distribution studies previously indicated that AKR1C2 (type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD)) and AKR1C3 (type 2 3alpha-HSD) are highly expressed in human prostate. An assessment of the directionality of these AKR1C isozymes in a cellular environment would help identify which isozymes are responsible for 5alpha-dihydrotestosterone (SaDHT) formation or its elimination in the prostate. An imbalance in 5alpha-DHT levels has been implicated in development of prostate carcinoma and benign prostatic hyperplasia. We focused our attention on AKR 1 C2 since this is the isoform that will oxidize 3alpha-androstanediol (3alpha-diol) to 5alpha-DHT in vitro, suggesting it could elevate 5alpha-DHT levels. To determine whether AKR1C2 preferentially functions as a reductase or an oxidase in a cellular context, we transiently transfected AKR 1 C2 (pcDNA3-AKR 1 C2) into COS-1 cells and stably transfected pcDNA3-AKR 1 C2 and pLNCXAKR1C2 constructs into PC-3 and LNCaP cells, respectively. COS-1 is a monkey kidney cell line, while PC-3 and LNCaP cells are androgen receptor (-) and (+) prostate adenocarcinoma cell lines, respectively. In transient COS-1AKR1C2 and in stable PC3-AKR1C2 transfectants, AKR1C2 functioned as a 3-ketosteroid reductase inactivating SaDHT. (Abstract truncated at 2000 characters)
Descriptors		PROSTATIC NEOPLASMS PROSTATIC HYPERPLASIA 3-HYDROXYSTEROID DEHYDROGENASES ANDROGENS HYDROXYTESTOSTERONES TUMOR CELLS, CULTURED TRANSFECTION POLYMERASE CHAIN REACTION