PMID- 16601286 OWN - NLM STAT- MEDLINE DCOM- 20060706 LR - 20171116 IS - 1351-0088 (Print) IS - 1351-0088 (Linking) VI - 13 IP - 1 DP - 2006 Mar TI - Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma. PG - 169-80 AB - Type 2 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) is a multi-functional enzyme that possesses 3alpha-, 17beta- and 20alpha-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3alpha-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of Delta(4)-androstene-3,17-dione to testosterone, 5alpha-dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), and 3alpha-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells. FAU - Fung, K-M AU - Fung KM AD - Department of Urology, University of Oklahoma Health Sciences Center, 920 Stanton L Young Blvd, WP3150, Oklahoma City, OK 73104, USA. FAU - Samara, E N S AU - Samara EN FAU - Wong, C AU - Wong C FAU - Metwalli, A AU - Metwalli A FAU - Krlin, R AU - Krlin R FAU - Bane, B AU - Bane B FAU - Liu, C Z AU - Liu CZ FAU - Yang, J T AU - Yang JT FAU - Pitha, J V AU - Pitha JV FAU - Culkin, D J AU - Culkin DJ FAU - Kropp, B P AU - Kropp BP FAU - Penning, T M AU - Penning TM FAU - Lin, Hsueh-Kung AU - Lin HK LA - eng GR - CA 97044/CA/NCI NIH HHS/United States GR - DK 47015/DK/NIDDK NIH HHS/United States GR - DK 54925/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Endocr Relat Cancer JT - Endocrine-related cancer JID - 9436481 RN - 0 (AR protein, human) RN - 0 (Antibodies, Monoclonal) RN - 0 (Receptors, Androgen) RN - EC 1.1.- (3-Hydroxysteroid Dehydrogenases) RN - EC 1.1.1.- (Hydroxyprostaglandin Dehydrogenases) RN - EC 1.1.1.357 (AKR1C3 protein, human) RN - EC 1.1.1.357 (Aldo-Keto Reductase Family 1 Member C3) SB - IM MH - 3-Hydroxysteroid Dehydrogenases/genetics/immunology/*metabolism MH - Adenocarcinoma/*enzymology/pathology MH - Aged MH - Aldo-Keto Reductase Family 1 Member C3 MH - Antibodies, Monoclonal/immunology MH - Blotting, Western MH - Epithelial Cells/enzymology MH - Gene Expression Regulation, Enzymologic/physiology MH - Humans MH - Hydroxyprostaglandin Dehydrogenases/genetics/immunology/*metabolism MH - Immunoenzyme Techniques MH - Male MH - Middle Aged MH - Prostate/*enzymology MH - Prostatic Neoplasms/*enzymology/pathology MH - Receptors, Androgen/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stromal Cells/enzymology/pathology MH - Tumor Cells, Cultured EDAT- 2006/04/08 09:00 MHDA- 2006/07/11 09:00 CRDT- 2006/04/08 09:00 PHST- 2006/04/08 09:00 [pubmed] PHST- 2006/07/11 09:00 [medline] PHST- 2006/04/08 09:00 [entrez] AID - 13/1/169 [pii] AID - 10.1677/erc.1.01048 [doi] PST - ppublish SO - Endocr Relat Cancer. 2006 Mar;13(1):169-80. doi: 10.1677/erc.1.01048.