Gene Symbol: AKR1C3
Description: aldo-keto reductase family 1 member C3
Alias: DD3, DDX, HA1753, HAKRB, HAKRe, HSD17B5, PGFS, hluPGFS, aldo-keto reductase family 1 member C3, 3-alpha hydroxysteroid dehydrogenase, type II, 3-alpha-HSD type II, brain, chlordecone reductase homolog HAKRb, dihydrodiol dehydrogenase 3, dihydrodiol dehydrogenase X, indanol dehydrogenase, prostaglandin F synthase, testosterone 17-beta-dehydrogenase 5, trans-1,2-dihydrobenzene-1,2-diol dehydrogenase, type IIb 3-alpha hydroxysteroid dehydrogenase
Species: human
Products:     AKR1C3

Top Publications

  1. Bains O, Grigliatti T, Reid R, Riggs K. Naturally occurring variants of human aldo-keto reductases with reduced in vitro metabolism of daunorubicin and doxorubicin. J Pharmacol Exp Ther. 2010;335:533-45 pubmed publisher
    ..wild-type counterparts: the A106T, R170C, and P180S variants significantly reduced metabolism compared with the AKR1C3 wild-type (V(max), 23-47% decrease; k(cat), 22-47%; k(cat)/K(m), 38-44%); the L311V variant of AKR1C4 ..
  2. Matsuura K, Shiraishi H, Hara A, Sato K, Deyashiki Y, Ninomiya M, et al. Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity. J Biochem. 1998;124:940-6 pubmed
    ..The properties of AKR1C3 have not been fully characterized compared to the other isoforms...
  3. MARIN Y, Seiberg M, Lin C. Aldo-keto reductase 1C subfamily genes in skin are UV-inducible: possible role in keratinocytes survival. Exp Dermatol. 2009;18:611-8 pubmed publisher
    ..AKR1C1 and AKR1C2 inactivate progesterone and 5alpha-dihydrotestosterone, respectively, whereas AKR1C3 activates oestradiol and testosterone...
  4. Dufort I, Rheault P, Huang X, Soucy P, Luu The V. Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase. Endocrinology. 1999;140:568-74 pubmed
  5. Wang S, Yang Q, Fung K, Lin H. AKR1C2 and AKR1C3 mediated prostaglandin D2 metabolism augments the PI3K/Akt proliferative signaling pathway in human prostate cancer cells. Mol Cell Endocrinol. 2008;289:60-6 pubmed publisher
    ..b>AKR1C3 possesses 11-ketoprostaglandin reductase activity and is capable of converting PGD2 to 9alpha, 11beta-PGF2alpha, ..
  6. Davies N, Hayden R, Simpson P, Birtwistle J, Mayer K, Ride J, et al. AKR1C isoforms represent a novel cellular target for jasmonates alongside their mitochondrial-mediated effects. Cancer Res. 2009;69:4769-75 pubmed publisher
    ..Although JA is the more potent inhibitor of recombinant AKR1C proteins, including the in vitro prostaglandin F synthase activity of AKR1C3, MeJ displayed greater potency in cellular systems that was, at least in part, due to ..
  7. Byrns M, Duan L, Lee S, Blair I, Penning T. Aldo-keto reductase 1C3 expression in MCF-7 cells reveals roles in steroid hormone and prostaglandin metabolism that may explain its over-expression in breast cancer. J Steroid Biochem Mol Biol. 2010;118:177-87 pubmed publisher
    Aldo-keto reductase (AKR) 1C3 (type 5 17beta-hydroxysteroid dehydrogenase and prostaglandin F synthase), may stimulate proliferation via steroid hormone and prostaglandin (PG) metabolism in the breast...
  8. Guise C, Abbattista M, Singleton R, Holford S, Connolly J, Dachs G, et al. The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Res. 2010;70:1573-84 pubmed publisher
    ..Plasmid-based expression of candidate genes identified aldo-keto reductase 1C3 as a novel nitroreductase. AKR1C3 protein was detected by Western blot in 7 of 23 cell lines and correlated with oxic PR-104A metabolism, an ..
  9. Milivojevic V, Kranzler H, Gelernter J, Burian L, Covault J. Variation in genes encoding the neuroactive steroid synthetic enzymes 5?-reductase type 1 and 3?-reductase type 2 is associated with alcohol dependence. Alcohol Clin Exp Res. 2011;35:946-52 pubmed publisher
    ..For 3?-HSD, we examined the nonsynonymous AKR1C3 SNP rs12529 (H5Q), which has been associated with bladder cancer...

More Information

Publications110 found, 100 shown here

  1. Penning T, Burczynski M, Jez J, Lin H, Ma H, Moore M, et al. Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3). Mol Cell Endocrinol. 2001;171:137-49 pubmed
    ..and is identical to type 2 3alpha-HSD and is a member of the aldo-keto reductase (AKR) superfamily; it is formally AKR1C3. In vitro the homogeneous recombinant enzyme expressed in Escherichia coli functions as a 3-keto-, 17-keto- and 20-..
  2. Fung K, Samara E, Wong C, Metwalli A, Krlin R, Bane B, et al. Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma. Endocr Relat Cancer. 2006;13:169-80 pubmed
    ..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-..
  3. Figueroa J, Malats N, Garcia Closas M, Real F, Silverman D, Kogevinas M, et al. Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes. Carcinogenesis. 2008;29:1955-62 pubmed publisher
    ..receptor (AHR), AHRR and aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4, SULT1A1 and SULT1A2)...
  4. Pfeiffer M, Smit F, Sedelaar J, Schalken J. Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer. Mol Med. 2011;17:657-64 pubmed publisher
    ..The androgen receptor (AR) and enzymes (AKR1C3, HSD17B2, HSD17B3, UGT2B15 and UGT2B17 ) that are involved in the metabolism of adrenal steroids were upregulated ..
  5. Lin H, Jez J, Schlegel B, Peehl D, Pachter J, Penning T. Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution. Mol Endocrinol. 1997;11:1971-84 pubmed
    ..This study is the first complete characterization of recombinant type 2 3alpha-HSD demonstrating dual activity and cellular distribution in the human prostate. ..
  6. Penning T, Burczynski M, Jez J, Hung C, Lin H, Ma H, et al. Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J. 2000;351:67-77 pubmed
    ..The enzymes correspond to type 1 3alpha-HSD (AKR1C4), type 2 3alpha(17beta)-HSD (AKR1C3), type 3 3alpha-HSD (AKR1C2) and 20alpha(3alpha)-HSD (AKR1C1), and share at least 84% amino acid sequence identity...
  7. Rizner T, Smuc T, Rupreht R, Sinkovec J, Penning T. AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer. Mol Cell Endocrinol. 2006;248:126-35 pubmed
    ..We next examined the expression of AKR1C1 and AKR1C3 (type 5 17beta-hydroxysteroid dehydrogenase) in 16 paired specimens of endometrial cancer and adjacent normal ..
  8. Azzarello J, Fung K, Lin H. Tissue distribution of human AKR1C3 and rat homolog in the adult genitourinary system. J Histochem Cytochem. 2008;56:853-61 pubmed publisher
    ..b>AKR1C3 is therefore implicated in regulating ligand access to the androgen receptor, estrogen receptor, and peroxisome ..
  9. Skarydová L, Zivna L, Xiong G, Maser E, Wsol V. AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids. Chem Biol Interact. 2009;178:138-44 pubmed publisher
    b>AKR1C3 (also known as 17beta-hydroxysteroid dehydrogenase type 5 or 3alpha-hydroxysteroid dehydrogenase type 2) functions as a 3-keto, 17-keto and 20-ketosteroid reductase and as a 3alpha-, 17beta- and 20alpha-hydroxysteroid oxidase...
  10. Hofland J, Van Weerden W, Dits N, Steenbergen J, van Leenders G, Jenster G, et al. Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. Cancer Res. 2010;70:1256-64 pubmed publisher
    ..Enzymes that convert androstenedione to testosterone (AKR1C3) and testosterone to dihydrotestosterone (DHT; SRD5A1) were abundantly expressed...
  11. Khanna M, Qin K, Wang R, Cheng K. Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases. J Biol Chem. 1995;270:20162-8 pubmed
    ..The type I gene contains a TATA box that is located 27 bp upstream of multiple transcription start sites. In contrast, the type II gene contains two tandem AP2 sequences juxtaposed to a single transcription start site. ..
  12. Suzuki Yamamoto T, Nishizawa M, Fukui M, Okuda Ashitaka E, Nakajima T, Ito S, et al. cDNA cloning, expression and characterization of human prostaglandin F synthase. FEBS Lett. 1999;462:335-40 pubmed
    A cDNA clone of prostaglandin F synthase (PGFS) was isolated from human lung by using cDNA of bovine lung-type PGFS as a probe and its protein expressed in Escherichia coli was purified to apparent homogeneity...
  13. Azzarello J, Lin H, Gherezghiher A, Zakharov V, Yu Z, Kropp B, et al. Expression of AKR1C3 in renal cell carcinoma, papillary urothelial carcinoma, and Wilms' tumor. Int J Clin Exp Pathol. 2009;3:147-55 pubmed
    ..b>AKR1C3 was initially identified as an enzyme involved in steroid metabolism...
  14. Furlan V, Konc J, Bren U. Inverse Molecular Docking as a Novel Approach to Study Anticarcinogenic and Anti-Neuroinflammatory Effects of Curcumin. Molecules. 2018;23: pubmed publisher
    ..We firmly believe that our computational results will complement and direct future experimental studies on curcumin's anticancer activity as well as on its therapeutic effects against Alzheimer's disease. ..
  15. Sagvekar P, Kumar P, Mangoli V, Desai S, Mukherjee S. DNA methylome profiling of granulosa cells reveals altered methylation in genes regulating vital ovarian functions in polycystic ovary syndrome. Clin Epigenetics. 2019;11:61 pubmed publisher
    ..Our findings suggest that the epigenetic dysregulation of genes involved in important processes associated with follicular development may contribute to ovarian defects observed in women with PCOS. ..
  16. Dirandeh E, Towhidi A, Pirsaraei Z, Saberifar T, Akhlaghi A, Roodbari A. The endometrial expression of prostaglandin cascade components in lactating dairy cows fed different polyunsaturated fatty acids. Theriogenology. 2015;83:206-12 pubmed publisher
    ..endometrial biopsies were prepared to evaluate the expression of genes related to prostaglandin cascade (prostaglandin F synthase [PGFS], prostaglandin E synthase [PGES], prostaglandin endoperoxide synthase-2 [PGHS-2]), phospholipase ..
  17. Ghosal A, Yuan Y, Tong W, Su A, Gu C, Chowdhury S, et al. Characterization of human liver enzymes involved in the biotransformation of boceprevir, a hepatitis C virus protease inhibitor. Drug Metab Dispos. 2011;39:510-21 pubmed publisher
    ..Screening of boceprevir with recombinant human aldo-keto reductases (AKRs) revealed that AKR1C2 and AKR1C3 exhibited catalytic activity with respect to the formation of M+2 metabolites (M28 and M31)...
  18. Sumantran V, Mishra P, Bera R, Sudhakar N. Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma. Pharmaceutics. 2016;8: pubmed publisher
    ..were up-regulated in psoriasis, whereas melanomas showed downregulation of genes regulating turnover of vitamin A (AKR1C3), and cholesterol (CYP39A1)...
  19. Mostaghel E, Zhang A, Hernandez S, Marck B, Zhang X, Tamae D, et al. Contribution of Adrenal Glands to Intratumor Androgens and Growth of Castration-Resistant Prostate Cancer. Clin Cancer Res. 2019;25:426-439 pubmed publisher
    ..for adrenal androgen utilization and nine expressed enzymes for de novo steroidogenesis (HSD3B1, CYP17A, AKR1C3, and HSD17B3). Mice are appropriate for evaluating adrenal impact of steroidogenesis inhibitors...
  20. Zapletal O, Prochazkova J, Dubec V, Hofmanova J, Kozubik A, Vondracek J. Butyrate interacts with benzo[a]pyrene to alter expression and activities of xenobiotic metabolizing enzymes involved in metabolism of carcinogens within colon epithelial cell models. Toxicology. 2018;412:1-11 pubmed publisher
    ..induction of NAD(P)H:quinone oxidoreductase 1 (NQO1) and UGT1A4 only in HCT-116 cells, and it even repressed AKR1C3 induction in HT-29 cells...
  21. Kwok A, Wang Y, Ho W. Cytotoxic and pro-oxidative effects of Imperata cylindrica aerial part ethyl acetate extract in colorectal cancer in vitro. Phytomedicine. 2016;23:558-65 pubmed publisher
    ..levels qRT-PCR revealed that transcripts of rate-limiting PGE2- and PGF2?-biosynthetic enzymes - COX-1, mPGES1 and AKR1C3 were notably up-regulated...
  22. Nicolao M, Cumino A. Biochemical and molecular characterization of the calcineurin in Echinococcus granulosus larval stages. Acta Trop. 2015;146:141-51 pubmed publisher
    ..In contrast, Eg-CaN-A was undetectable during the pre-microcyst closing stage while a high DDX-like RNA helicase expression was evidenced...
  23. O Brien E, Lin D, Fuglestad B, Stetz M, Gosse T, Tommos C, et al. Improving yields of deuterated, methyl labeled protein by growing in H2O. J Biomol NMR. 2018;71:263-273 pubmed publisher
    ..are demonstrated for the membrane protein sensory rhodopsin II and the soluble proteins human aldoketoreductase AKR1c3, human ubiquitin, and bacterial flavodoxin...
  24. Lee Y, Bae J, Kang S, Cho S, Chun D, Nam S, et al. Pro-oxidant status and Nrf2 levels in psoriasis vulgaris skin tissues and dimethyl fumarate-treated HaCaT cells. Arch Pharm Res. 2017;40:1105-1116 pubmed publisher
    ..showed increased protein oxidation as well as down-regulation of Nrf2 and its regulatory proteins such as HO-1 and AKR1C3. Using HaCaT cells to model DMF-induced pro-oxidant effects in the skin cells, we found that DMF treatment induced ..
  25. Andrýs R, Zemanová L, Lenčo J, Bílková Z, Wsól V. Carbonyl-reducing enzymes as targets of a drug-immobilised affinity carrier. Chem Biol Interact. 2015;234:169-77 pubmed publisher
    ..of the presented carrier was demonstrated with pure recombinant enzymes (AKR1A1, AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C3, AKR1C4, CBR1 and CBR3) as well as with two model biological samples (cell extract from genetically modified ..
  26. Fokidis H, Yieng Chin M, Ho V, Adomat H, Soma K, Fazli L, et al. A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice. J Steroid Biochem Mol Biol. 2015;150:35-45 pubmed publisher
    ..pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P = 0...
  27. Korkegian A, Roberts D, Blair R, Parish T. Mutations in the essential arabinosyltransferase EmbC lead to alterations in Mycobacterium tuberculosis lipoarabinomannan. J Biol Chem. 2014;289:35172-81 pubmed publisher
    ..The GT-C motif contains two aspartate residues essential for function in the DDX motif. The proline-rich region contains two highly conserved asparagines (Asn-638 and Asn-652)...
  28. Hagberg Thulin M, Nilsson M, Thulin P, Céraline J, Ohlsson C, Damber J, et al. Osteoblasts promote castration-resistant prostate cancer by altering intratumoral steroidogenesis. Mol Cell Endocrinol. 2016;422:182-191 pubmed publisher
    ..LNCaP-19 cells displayed an increased expression of genes encoding for steroidogenic enzymes (CYP11A1, HSD3B1, and AKR1C3), estrogen signaling-related genes (CYP19A1, and ESR2), and genes for DHT-inactivating enzymes (UGT2B7, UGT2B15, ..
  29. Tan C, Shard C, Ranieri E, Hynes K, Pham D, Leach D, et al. Mutations of protocadherin 19 in female epilepsy (PCDH19-FE) lead to allopregnanolone deficiency. Hum Mol Genet. 2015;24:5250-9 pubmed publisher
    ..Both mRNA and protein levels of AKR1C3 were significantly decreased in PCDH19-FE patients...
  30. Lee R, Lee W, Park H, Ha W, Woo J, Chung H, et al. Stage-specific expression of DDX4 and c-kit at different developmental stages of the porcine testis. Anim Reprod Sci. 2018;190:18-26 pubmed publisher
    ..were located on the lumenal side, compared to synaptonemal complex protein 3-positive primary spermatocytes, but DDX-4 was not co-expressed with acrosin, a known acrosome marker. In addition, DDX4 was detected in PGP9...
  31. Rödelsperger C, Menden K, Serobyan V, Witte H, Baskaran P. First insights into the nature and evolution of antisense transcription in nematodes. BMC Evol Biol. 2016;16:165 pubmed publisher
    ..20 nematode genomes, showing that the majority of pairs is lineage-specific and even the highly conserved vps-4, ddx-27, and sel-2 loci show abundant structural changes including duplications, deletions, intron gains and loss of ..
  32. Sharip Z, Hashim N, Suratman S. Occurrence of organochlorine pesticides in a tropical lake basin. Environ Monit Assess. 2017;189:560 pubmed publisher
    ..The highest concentrations of pesticide residues were found in October. DDX and ?/? ratios indicate possible fresh inputs of the OCP pesticide in the basin.
  33. Tchernof A, Mansour M, Pelletier M, Boulet M, Nadeau M, Luu The V. Updated survey of the steroid-converting enzymes in human adipose tissues. J Steroid Biochem Mol Biol. 2015;147:56-69 pubmed publisher
    ..Our work on 20α-HSD (AKR1C1), 3α-HSD type 3 (AKR1C2) and 17β-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function...
  34. Hammond J, Zhou L, Lamichhane R, Chu H, Millar D, Gerace L, et al. A Survey of DDX21 Activity During Rev/RRE Complex Formation. J Mol Biol. 2018;430:537-553 pubmed publisher
    ..A conserved binding interaction between DDX protein's DEAD domain and Rev was identified, with Rev's nuclear diffusion inhibitory signal motif playing a ..
  35. Ashley R, Yu Z, Fung K, Frimberger D, Kropp B, Penning T, et al. Developmental evaluation of aldo-keto reductase 1C3 expression in the cryptorchid testis. Urology. 2010;76:67-72 pubmed publisher
    To characterize aldo-keto reductase 1C3 (AKR1C3) expression in surgically-removed cryptorchid testes. Human AKR1C3 is a monomeric, cytoplasmic, multifunctional enzyme that reduces ketosteroids, ketoprostaglandins, and lipid aldehydes...
  36. Tian Y, Zhao L, Zhang H, Liu X, Zhao L, Zhao X, et al. AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression. Diagn Pathol. 2014;9:42 pubmed publisher
    Aldo-keto reductase family 1 member C3 (AKR1C3) is a key steroidogenic enzyme that is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC)...
  37. Kawaguchi Y, Mizuno H, Horikawa M, Kano M, Yamada K, Yamakawa F, et al. Virilism and Ectopic Expression of HSD17B5 in Mature Cystic Teratoma. Tohoku J Exp Med. 2017;241:125-129 pubmed publisher
    ..Immunohistochemical analysis demonstrated marked immunoreactivity of 17beta-hydroxysteroid dehydrogenase (HSD17B5), an enzyme that can convert androstenedione to testosterone...
  38. Lewis M, Wiebe J, Heathcote J. Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma. BMC Cancer. 2004;4:27 pubmed
    ..expression (as a ratio of 18S rRNA) of 5alphaR type 1 (SRD5A1), 5alphaR type 2 (SRD5A2), 3alpha-HSO type 2 (AKR1C3), 3alpha-HSO type 3 (AKR1C2) and 20alpha-HSO (AKR1C1) mRNAs in paired (tumorous and nontumorous) breast tissues ..
  39. Moradi Manesh D, El Hoss J, Evans K, Richmond J, Toscan C, Bracken L, et al. AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia. Blood. 2015;126:1193-202 pubmed publisher
    ..Originally designed to target hypoxic cells, PR-104A is independently activated by aldo-keto-reductase 1C3 (AKR1C3). The aim of this study was to test whether AKR1C3 is a predictive biomarker of in vivo PR-104 sensitivity...
  40. Mowday A, Ashoorzadeh A, Williams E, Copp J, Silva S, Bull M, et al. Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy. Biochem Pharmacol. 2016;116:176-87 pubmed publisher
    ..the human one- and two-electron oxidoreductases cytochrome P450 oxidoreductase (POR) and aldo-keto reductase 1C3 (AKR1C3)...
  41. Ferreira A, Grossmann J, Fortes C, Kilminster T, Scanlon T, Milton J, et al. The sheep (Ovis aries) muscle proteome: Decoding the mechanisms of tolerance to Seasonal Weight Loss using label-free proteomics. J Proteomics. 2017;161:57-67 pubmed publisher
    ..immunoglobulin V lambda chain; transgelin; fatty acid synthase; glutathione S-transferase A2; dihydrodiol dehydrogenase 3-like...
  42. Malátková P, Sokolová S, Chocholoušová Havlíková L, Wsól V. Carbonyl reduction of warfarin: Identification and characterization of human warfarin reductases. Biochem Pharmacol. 2016;109:83-90 pubmed publisher
    ..Furthermore, of nine recombinant cytosolic carbonyl reducing enzymes tested for their ability to reduce warfarin, AKR1C3 and CBR1 were identified as warfarin reductases and their kinetic parameters were determined...
  43. Sausville L, Jones C, Aldrich M, Blot W, Pozzi A, Williams S. Genetic variation in the eicosanoid pathway is associated with non-small-cell lung cancer (NSCLC) survival. PLoS ONE. 2017;12:e0180471 pubmed publisher
    ..rare variants in ALOX15B (arachidonate 15-lipoxygenase, type B) and the common variant rs12529 in AKR1C3 (prostaglandin F synthase) were associated with NSCLC mortality in women and African Americans, respectively...
  44. Gai M, Bo Q, Qi L. Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer. Biochem Biophys Res Commun. 2016;469:1000-5 pubmed publisher
    ..However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown...
  45. Zheng X, Wu Y, Wu D, Wang X, Zhang C, Guo X, et al. 3D-QSAR studies of 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids as AKR1C3 inhibitors: Highlight the importance of molecular docking in conformation generation. Bioorg Med Chem Lett. 2016;26:5631-5638 pubmed publisher
    b>AKR1C3 is a promising drug target for castration-resistant prostate cancer (CRPC)...
  46. Borrelli R, Tcaciuc A, Verginelli I, Baciocchi R, Guzzella L, Cesti P, et al. Performance of passive sampling with low-density polyethylene membranes for the estimation of freely dissolved DDx concentrations in lake environments. Chemosphere. 2018;200:227-236 pubmed publisher
    ..for assessing the freely dissolved concentrations of DDT and its degradates (DDD and DDE, together referred to as DDx) in an Italian lake environment...
  47. Ruiz F, Porté S, Gallego O, Moro A, Ardèvol A, del Rio Espinola A, et al. Retinaldehyde is a substrate for human aldo-keto reductases of the 1C subfamily. Biochem J. 2011;440:335-44 pubmed publisher
    ..The kcat values were also low (0.18-0.6 min-1), except for AKR1C3 reduction of 9-cis-retinaldehyde whose kcat was remarkably higher (13 min-1)...
  48. Matsunaga T, Hojo A, Yamane Y, Endo S, El Kabbani O, Hara A. Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers. Chem Biol Interact. 2013;202:234-42 pubmed publisher
    ..Among the six AKRs, AKR1C1 and AKR1C3 are highly induced with the CDDP resistance...
  49. Doig C, Battaglia S, Khanim F, Bunce C, Campbell M. Knockdown of AKR1C3 exposes a potential epigenetic susceptibility in prostate cancer cells. J Steroid Biochem Mol Biol. 2016;155:47-55 pubmed publisher
    The aldo-keto reductase 1C3 (AKR1C3) has been heavily implicated in the propagation of prostate malignancy...
  50. Pippione A, Giraudo A, Bonanni D, Carnovale I, Marini E, Cena C, et al. Hydroxytriazole derivatives as potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors discovered by bioisosteric scaffold hopping approach. Eur J Med Chem. 2017;139:936-946 pubmed publisher
    The aldo-keto reductase 1C3 isoform (AKR1C3) plays a vital role in the biosynthesis of androgens, making this enzyme an attractive target for castration-resistant prostate cancer therapy...
  51. Hofland J, Van Weerden W, Steenbergen J, Dits N, Jenster G, de Jong F. Activin A stimulates AKR1C3 expression and growth in human prostate cancer. Endocrinology. 2012;153:5726-34 pubmed publisher
    ..Activin A induced the expression and enzyme activity of 17?-hydroxysteroid dehydrogenase enzyme AKR1C3 in LNCaP and VCaP cells...
  52. Oktay K, Baltaci V, Sonmezer M, Turan V, Unsal E, BaltacI A, et al. Oogonial Precursor Cell-Derived Autologous Mitochondria Injection to Improve Outcomes in Women With Multiple IVF Failures Due to Low Oocyte Quality: A Clinical Translation. Reprod Sci. 2015;22:1612-7 pubmed publisher
    ..from laparoscopically obtained ovarian cortical pieces by cell sorting using a monoclonal anti-vasa homolog (anti-DDX) antibody. They were then disrupted and mitochondria were isolated...
  53. Malátková P, Kanavi M, Nobilis M, Wsol V. In vitro metabolism of fenofibric acid by carbonyl reducing enzymes. Chem Biol Interact. 2016;258:153-8 pubmed publisher
    ..AKR1C1, AKR1C2, AKR1C3 and AKR1B1 were also identified as reductases of fenofibric acid but are expected to play only a minor role in ..
  54. O Reilly M, Kempegowda P, Walsh M, Taylor A, Manolopoulos K, Allwood J, et al. AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2017;102:3327-3339 pubmed publisher
    ..We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS...
  55. Birtwistle J, Hayden R, Khanim F, Green R, Pearce C, Davies N, et al. The aldo-keto reductase AKR1C3 contributes to 7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol mediated oxidative DNA damage in myeloid cells: implications for leukemogenesis. Mutat Res. 2009;662:67-74 pubmed publisher
    The aldo-keto reductase AKR1C3, has been shown to regulate myelopoiesis via its ability to metabolise prostaglandin D2 (PGD2)...
  56. Hirakawa H, Sawada H, Yamahama Y, Takikawa S, Shintaku H, Hara A, et al. Expression analysis of the aldo-keto reductases involved in the novel biosynthetic pathway of tetrahydrobiopterin in human and mouse tissues. J Biochem. 2009;146:51-60 pubmed publisher
    ..For this reason, a patient with SPR deficiency may show progressive neurological deterioration without HPA, and SPR knockout mice may exhibit HPA and abnormal locomotion activity. ..
  57. Ke L, Che Y, Cao Y, Wu X, Hu Y, Sun H, et al. Polymorphisms of the HSD17B6 and HSD17B5 genes in Chinese women with polycystic ovary syndrome. J Womens Health (Larchmt). 2010;19:2227-32 pubmed publisher
    To investigate the polymorphisms of the 17?-hydroxysteroid dehydrogenase type 5 and type 6 (HSD17B5 and HSD17B6) genes in Chinese women with polycystic ovary syndrome (PCOS)...
  58. Kang S, Liu S, Wang H, Cai W. Enhanced degradation performances of plate-like micro/nanostructured zero valent iron to DDT. J Hazard Mater. 2016;307:145-53 pubmed publisher
    ..experiments have shown that more than 50% of DDT can be mineralized in 20min and the rest is dechlorinated to DDX (the products with less chlorine)...
  59. Han X, Zheng T, Lan Q, Zhang Y, Kilfoy B, Qin Q, et al. Genetic polymorphisms in nitric oxide synthase genes modify the relationship between vegetable and fruit intake and risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2009;18:1429-38 pubmed publisher
    ..Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the NOS genes, modify the association between vegetable and fruit intake and risk of NHL. ..
  60. Fujisawa Y, Sakaguchi K, Ono H, Yamaguchi R, Kato F, Kagami M, et al. Combined steroidogenic characters of fetal adrenal and Leydig cells in childhood adrenocortical carcinoma. J Steroid Biochem Mol Biol. 2016;159:86-93 pubmed publisher
    ..CYP17A1, POR, HSD17B3, and SULT2A1, a low but similar expression of CYB5A, and reduced expressions of AKR1C3 (HSD17B5) and HSD3B2. Notably, a Leydig cell marker INSL3 was expressed at a low but detectable level in the c-ACC...
  61. Begemann M, Sargin D, Rossner M, Bartels C, Theis F, Wichert S, et al. Episode-specific differential gene expression of peripheral blood mononuclear cells in rapid cycling supports novel treatment approaches. Mol Med. 2008;14:546-52 pubmed publisher
    ..elevated in depressed episodes were prostaglandin D synthetase (PTGDS) and prostaglandin D2 11-ketoreductase (AKR1C3), both involved in hibernation. We hypothesized them to account for some of the rapid cycling symptoms...
  62. Bennett M, Schlegel B, Jez J, Penning T, Lewis M. Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+. Biochemistry. 1996;35:10702-11 pubmed
    ..Knowledge of the position of this water molecule, combined with the stereochemistry of hydride transfer, suggests that the alpha face of a bound steroid will be oriented toward the side of the apolar cleft containing Trp 86. ..
  63. Mantel A, Carpenter Mendini A, Vanbuskirk J, De Benedetto A, Beck L, Pentland A. Aldo-keto reductase 1C3 is expressed in differentiated human epidermis, affects keratinocyte differentiation, and is upregulated in atopic dermatitis. J Invest Dermatol. 2012;132:1103-10 pubmed publisher
    Aldo-keto reductase 1C3 (AKR1C3) has been shown to mediate the metabolism of sex hormones and prostaglandin D(2) (PGD(2)), a lipid mediator that promotes skin inflammation in atopic dermatitis (AD)...
  64. Milivojevic V, Feinn R, Kranzler H, Covault J. Variation in AKR1C3, which encodes the neuroactive steroid synthetic enzyme 3?-HSD type 2 (17?-HSD type 5), moderates the subjective effects of alcohol. Psychopharmacology (Berl). 2014;231:3597-608 pubmed publisher
    ..We previously reported that a common nonsynonymous polymorphism, AKR1C3 2 in the gene encoding the enzyme 3?-HSD2/17?-HSD5, and a synonymous single nucleotide polymorphism (SNP), ..
  65. Mantel A, Carpenter Mendini A, VanBuskirk J, Pentland A. Aldo-keto reductase 1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism. Exp Dermatol. 2014;23:573-8 pubmed publisher
    Aldo-keto reductase 1C3 (AKR1C3) is an enzyme involved in metabolizing prostaglandins (PGs) and sex hormones...
  66. Udhane S, Dick B, Hu Q, Hartmann R, Pandey A. Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis. Biochem Biophys Res Commun. 2016;477:1005-1010 pubmed publisher
    ..galeterone altered the expression of HSD3B2 but orteronel did not change the expression of HSD3B2, CYP17A1 and AKR1C3. The CYP19A1 activity was not inhibited except by compound IV which lowered activity by 23%...
  67. Sakurai M, Oishi K, Watanabe K. Localization of cyclooxygenases-1 and -2, and prostaglandin F synthase in human kidney and renal cell carcinoma. Biochem Biophys Res Commun. 2005;338:82-6 pubmed
  68. Roberts R, Bergstralh E, Farmer S, Jacobson D, Hebbring S, Cunningham J, et al. Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia. Prostate. 2006;66:392-404 pubmed
    ..3, 95% CI=1.2, 4.4). In multivariate analyses, the homozygous variant genotypes of AKR1C3 (c.15 G/A and c.90 G/A) were associated with a decreased risk of an enlarged prostate (HR=0.56, 95% CI=0.35, 0...
  69. Vaarala M, Mattila H, Ohtonen P, Tammela T, Paavonen T, Schleutker J. The interaction of CYP3A5 polymorphisms along the androgen metabolism pathway in prostate cancer. Int J Cancer. 2008;122:2511-6 pubmed publisher
    ..For prostate cancer patients aged below 65 years, the OR for interaction of CYP3A5*1/*3 or *1/*1 and AKR1C3 Q5H CC genotypes was 1.84 with 95% CI 1.03-3.28...
  70. Marioli D, Saltamavros A, Vervita V, Koika V, Adonakis G, Decavalas G, et al. Association of the 17-hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) with hyperandrogenemia in polycystic ovary syndrome (PCOS). Fertil Steril. 2009;92:648-52 pubmed publisher
    ..polymorphism (SNP) at position -71 of the promoter of 17beta-hydroxysteroid dehydrogenase type 5 gene (-71A/G HSD17B5 SNP) and polycystic ovary syndrome (PCOS) in a well characterized cohort of caucasian PCOS women with biochemical ..
  71. Khanna M, Qin K, Klisak I, Belkin S, Sparkes R, Cheng K. Localization of multiple human dihydrodiol dehydrogenase (DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome 10 by the polymerase chain reaction and fluorescence in situ hybridization. Genomics. 1995;25:588-90 pubmed
    ..All three genes were found to be located on chromosome 10. In situ hybridization using a lambda clone as the probe further confirmed regional localization at 10p14-p15. ..
  72. Qin K, Ehrmann D, Cox N, Refetoff S, Rosenfield R. Identification of a functional polymorphism of the human type 5 17beta-hydroxysteroid dehydrogenase gene associated with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91:270-6 pubmed
    ..Our objective was to investigate the role of a potentially activating 17beta-HSD5 gene (HSD17B5) variant in hyperandrogenism...
  73. Jackson V, Yosaatmadja Y, Flanagan J, Squire C. Structure of AKR1C3 with 3-phenoxybenzoic acid bound. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012;68:409-13 pubmed publisher
    Aldo-keto reductase 1C3 (AKR1C3) is a human enzyme that catalyzes the NADPH-dependent reduction of steroids and prostaglandins...
  74. Jernberg E, Thysell E, Bovinder Ylitalo E, Rudolfsson S, Crnalic S, Widmark A, et al. Characterization of prostate cancer bone metastases according to expression levels of steroidogenic enzymes and androgen receptor splice variants. PLoS ONE. 2013;8:e77407 pubmed publisher
    ..Significantly higher levels of SRD5A1, AKR1C2, AKR1C3, and HSD17B10 mRNA were however found in bone metastases than in non-malignant and/or malignant prostate tissue, ..
  75. Xia D, Lai D, Wu W, Webb Z, Yang Q, Zhao L, et al. Transition from androgenic to neurosteroidal action of 5α-androstane-3α, 17β-diol through the type A γ-aminobutyric acid receptor in prostate cancer progression. J Steroid Biochem Mol Biol. 2018;178:89-98 pubmed publisher
    ..Aldo-keto reductase family 1 member C3 (AKR1C3), a multi-functional steroid metabolizing enzyme, is specifically expressed in the cytoplasm of PCa cells; and ..
  76. Bonner M, Rothman N, Mumford J, He X, Shen M, Welch R, et al. Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer. Mutat Res. 2005;582:53-60 pubmed
    ..in 8-oxoguanine-DNA glycosylase (OGG1), glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase 1C3 (AKR1C3) modify such an association...
  77. Matsunaga T, Arakaki M, Kamiya T, Endo S, El Kabbani O, Hara A. Involvement of an aldo-keto reductase (AKR1C3) in redox cycling of 9,10-phenanthrenequinone leading to apoptosis in human endothelial cells. Chem Biol Interact. 2009;181:52-60 pubmed publisher
    ..and kinetic constants in the 9,10-PQ reduction among 10 human reductases suggests that aldo-keto reductase 1C3 (AKR1C3) is a 9,10-PQ reductase in HAECs...
  78. Mantel A, Newsome A, Thekkudan T, Frazier R, Katdare M. The role of aldo-keto reductase 1C3 (AKR1C3)-mediated prostaglandin D2 (PGD2) metabolism in keloids. Exp Dermatol. 2016;25:38-43 pubmed publisher
    ..J2(15d-PGJ2) or enzymatically metabolized to 9α,11β-PGF2 by aldo-keto reductase 1C3 (AKR1C3)...
  79. Xu D, Aka J, Wang R, Lin S. 17beta-hydroxysteroid dehydrogenase type 5 is negatively correlated to apoptosis inhibitor GRP78 and tumor-secreted protein PGK1, and modulates breast cancer cell viability and proliferation. J Steroid Biochem Mol Biol. 2017;171:270-280 pubmed publisher
    ..We thus propose that 17?-HSD5 may not be a potent target for breast cancer treatment but its low expression could represent a poor prognosis factor. ..
  80. Migita T, Takayama K, Urano T, Obinata D, Ikeda K, Soga T, et al. ACSL3 promotes intratumoral steroidogenesis in prostate cancer cells. Cancer Sci. 2017;108:2011-2021 pubmed publisher
    ..ACSL3 overexpression led to upregulation of several genes such as aldo-keto reductase 1C3 (AKR1C3) involved in steroidogenesis, which utilizes adrenal androgen dehydroepiandrosterone sulfate (DHEAS) as substrate, ..
  81. Hara A, Endo S, Matsunaga T, Soda M, Yashiro K, El Kabbani O. Long-chain fatty acids inhibit human members of the aldo-keto reductase 1C subfamily. J Biochem. 2017;162:371-379 pubmed publisher
    ..77 µM), palmitoleic acid (Ki 0.41 µM) and linoleic acid (Ki 0.33 µM), respectively. AKR1C3 was the most sensitive to FA inhibition, showing low Ki values (0.23-0...
  82. Qin K, New M, Cheng K. Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol. 1993;46:673-9 pubmed
    ..also detected in the brain, kidney, lung, and testis, whereas the placenta expressed only the messenger RNA for HAKRb. Genomic blot analysis using HAKRb as the probe detected multiple DNA fragments hybridized to the probe and a high ..
  83. Griffin L, Mellon S. Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc Natl Acad Sci U S A. 1999;96:13512-7 pubmed
    ..Our results may thus help explain the rapid alleviation of the anxiety and dysphoria associated with late luteal phase dysphoria disorder and major unipolar depression by these SSRIs. ..
  84. Lin S, Shi R, Qiu W, Azzi A, Zhu D, Dabbagh H, et al. Structural basis of the multispecificity demonstrated by 17beta-hydroxysteroid dehydrogenase types 1 and 5. Mol Cell Endocrinol. 2006;248:38-46 pubmed
    ..Type 5 17beta-HSD (AKR1C3) differs significantly from the type 1 enzyme by possessing a spacious and flexible steroid-binding site...
  85. Svensson P, Gabrielsson B, Jernas M, Gummesson A, Sjöholm K. Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue. Cell Mol Biol Lett. 2008;13:599-613 pubmed publisher
    Aldoketoreductase 1C3 (AKR1C3) is a functional prostaglandin F synthase and a negative modulator of the availability of ligands for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma)...
  86. Tamae D, Mostaghel E, Montgomery B, Nelson P, Balk S, Kantoff P, et al. The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer. Chem Biol Interact. 2015;234:332-8 pubmed publisher
    ..in conversion of Δ(4)-androstene-3,17-dione and 5α-androstanedione to T and DHT, respectively, is catalyzed by AKR1C3. We therefore present the case that in the context of the DHEA-S depot, P450c17 and AKR1C3 inhibition may be an ..
  87. Munkholm K, Peijs L, Kessing L, Vinberg M. Reduced mRNA expression of PTGDS in peripheral blood mononuclear cells of rapid-cycling bipolar disorder patients compared with healthy control subjects. Int J Neuropsychopharmacol. 2014;18: pubmed publisher
    ..the conversion of prostaglandin H2 to prostaglandin D2 (PGD2), and the aldo-keto reductase family 1 member C3 (AKR1C3), which catalyzes the reduction of PGD2...
  88. Endo S, Matsunaga T, Ohta C, Soda M, Kanamori A, Kitade Y, et al. Roles of rat and human aldo-keto reductases in metabolism of farnesol and geranylgeraniol. Chem Biol Interact. 2011;191:261-8 pubmed publisher
    ..Human reductases with similar specificity were identified as AKR1B10 and AKR1C3, which most efficiently reduced farnesal and geranylgeranial among seven enzymes in the AKR1A-1C subfamilies...
  89. Lan Q, Mumford J, Shen M, DeMarini D, Bonner M, He X, et al. Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions. Carcinogenesis. 2004;25:2177-81 pubmed
    ..We therefore examined the association between single nucleotide polymorphisms (SNPs) in four genes (AKR1C3-Gln5His, NQO1-Pro187Ser, MnSOD-Val16Ala and OGG1-Ser326Cys) that play a role in the generation, prevention or ..
  90. Karunasinghe N, Zhu Y, Han D, Lange K, Zhu S, Wang A, et al. Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?. BMC Urol. 2016;16:48 pubmed publisher
    ..Genotyping of these men was carried out for the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP)...
  91. Bertelloni S, Maggio M, Federico G, Baroncelli G, Hiort O. 17beta-hydroxysteroid dehydrogenase-3 deficiency: a rare endocrine cause of male-to-female sex reversal. Gynecol Endocrinol. 2006;22:488-94 pubmed
    ..The clinical, endocrine and genetic features of 17beta-HSD3 deficiency are also reviewed. ..
  92. Lee Y, Lee G, Baek B, Heo S, Won S, Im J, et al. Cadmium-induced up-regulation of aldo-keto reductase 1C3 expression in human nasal septum carcinoma RPMI-2650 cells: Involvement of reactive oxygen species and phosphatidylinositol 3-kinase/Akt. Environ Toxicol Pharmacol. 2011;31:469-78 pubmed publisher
    ..The intracellular ROS levels were induced by cadmium treatment. In addition, cadmium elicited the AKR1C3 expression...