Regulation of 17beta-hydroxysteroid dehydrogenase type 2, type 4 and type 5 by calcitriol, LXR agonist and 5alpha-dihydrotestosterone in human prostate cancer cells.
Vitamin D seems to be involved in the control of prostate cancer cell growth. 17beta-Hydroxysteroid dehydrogenases type 2, type 4 and type 5 are enzymes which regulate intracellular concentration of active sex steroid hormones, which in turn, regulate the development, growth, and function of the prostate and play a role in the development and progression of prostate cancer. Using quantitative real-time PCR we find that calcitriol up-regulates HSD17B type 2, type 4 and type 5 in human prostate cancer LNCaP and PC3 cells but not in stromal cells. LXR agonist, TO-901317, suppresses the expression of HSD17B2 mRNA and inhibits calcitriol induced HSD17B2 expression. TO-901317 up-regulates the expression of HSD17B5 but not that of HSD17B4. 5alpha-Dihydrotestosterone up-regulates the expression of HSD17B2 and HSD17B4 but it significantly inhibits HSD17B5 expression by 70%. Calcitriol has no effect on DHT mediated expression of the three genes. The regulation of HSD17B2, HSD17B4 and HSD17B5 by ligands of LXR and VDR as well as AR in prostate cancer cells suggests a complex interaction of these signaling systems in the prostate.
Wang
Jing-Huan
JH
Department of Anatomy, Medical School, 33014 University of Tampere, Tampere, Finland. Jinghuan.Wang@uta.fi
Tuohimaa
Pentti
P
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis*; D015096:3-Hydroxysteroid Dehydrogenases; D000074425:Aldo-Keto Reductase Family 1 Member C3; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000819:agonists*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004789:Enzyme Activation; D004960:Estradiol Dehydrogenases / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006836:Hydro-Lyases / Q000096:biosynthesis*; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D006911:Hydroxyprostaglandin Dehydrogenases; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors; D064029:Peroxisomal Multifunctional Protein-2; D011467:Prostate / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D017154:Stromal Cells / Q000201:enzymology; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D000074425:Aldo-Keto Reductase Family 1 Member C3; D002117:Calcitriol; D004268:DNA-Binding Proteins; D013196:Dihydrotestosterone; D004960:Estradiol Dehydrogenases; D006836:Hydro-Lyases; D006845:Hydrocarbons, Fluorinated; D006911:Hydroxyprostaglandin Dehydrogenases; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D064029:Peroxisomal Multifunctional Protein-2; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C487341:AKR1C3 protein, human; C523763:HSD17B2 protein, human; C104587:HSD17B4 protein, human