Recombinant Human Aldo-keto reductase family 1 member C3(AKR1C3)

1. Genotype data on the AKR1C3 rs12529 SNP indicates that all three prostate cancer groups (New Zealanders, African Americans, and Caucasian Americans) have similar genotype and allele frequencies. The highest percentage of high-risk PC as a percentage of all PC were recorded for ever-smoker AA men with the AKR1C3 rs12529 CC genotype while the lowest was recorded for never-smoker NZ men with the CG+GG genotypes. PMID: 29920533
2. AKR1C3 is a novel epithelial-mesenchymal transition driver in prostate cancer metastasis through activating ERK signaling. PMID: 30139661
3. The GG genotype of AKR1C3 rs10508293 is associated with decreased risk for preeclampsia. PMID: 29777907
4. AKR1C3 transcriptional regulation and its role in prostate cancer progression [review] PMID: 28359237
5. Overexpression of AKR1C3 could result in the accumulation of prostaglandin F2alpha (PGF2alpha), which can not only promote prostate cancer cell 's proliferation but also could enhance prostate cancer cells resistance to radiation. PMID: 27385003
6. The replacement of C154 with a residue possessing a bulky aromatic side-chain impairs the folding of the alpha-helix containing C154 and its neighboring secondary structures, leading to low thermostability of AKR1C3. PMID: 28025170
7. Data suggest that, in breast cancer cells, expression of HSD17B5 and expression of GRP78 (an apoptosis inhibitor) are strongly but negatively correlated; GRP78 knockdown decreases breast cancer cell viability whereas HSD17B5 knockdown increases cell viability and cell proliferation. (HSD17B5, 17-beta-hydroxysteroid dehydrogenase 5; GRP78, 78 kDa glucose-regulated protein) PMID: 28457968
8. AKR1C3 is the primary enzyme and CBR1 is a minor enzyme responsible for warfarin reduction in human liver cytosol. PMID: 27055738
9. the present study suggests that AKR1C1, AKR1C2, AKR1C3, and AKR1C4 are closely associated with drug resistance to both CDDP and 5FU, and that mefenamic acid, an inhibitor of AKR1C, restores sensitivity through inhibition of drug-resistance in human cancer cells. PMID: 28259989
10. a variant in the promoter region of HSD17B5 related to fetal androgen synthesis influences the genital phenotype in 21-Hydroxylase Deficiency females. PMID: 27082632
11. Five common AKR1C3 polymorphisms were associated with decreased rates of exemestane catalysis. PMID: 27111237
12. If our these findings can be reproduced in larger homogeneous cohorts, a genetic stratification based on the AKR1C3 rs12529 single nucleotide polymorphism, can minimize androgen deprivation therapy-related health-related quality of life effects in prostate cancer patients PMID: 27485119
13. We identified strong associations between the studied AKR1C3 variants and UBC risk. The homozygous variant genotype of rs12529 was found to be inversely associated with UBC, and rs1937920 was shown to be associated with increased risk of UBC. None of the genotypes were found to be significantly associated with tumor characteristics. PMID: 27085562
14. aldo-keto reductase 1C3-mediated prostaglandin D2 metabolism has a role in keloids PMID: 26308156
15. The results suggest that decreased expression of AKR1C3 may be involved in development of gastric cancer and can be restored by Sodium Butyrate. PMID: 27019068
16. AKR1C3 expression is elevated in prostate cancer cell lines and primary prostate cancer, suggesting a link between AKR1C3 levels and the epigenetic status in prostate cancer cells. PMID: 26429394
17. Aldo-keto reductase 1C3 is overexpressed in skin squamous cell carcinoma (SCC). AKR1C3 affects SCC growth via prostaglandin metabolism. PMID: 24917395
18. these results indicated that the actions of AKR1C3 can produce FP receptor ligands whose activation results in carcinoma cell survival in breast cancer. PMID: 26170067
19. and AKR1C3 may serve as a valuable therapeutic target in the treatment of castration-resistant prostate cancer PMID: 25754347
20. AKR1C3 activation is a critical resistance mechanism associated with enzalutamide resistance. PMID: 25649766
21. In the present study, crystal structures of complexes of HSD17B5 with structurally diverse inhibitors derived from high-throughput screening were determined. PMID: 25849402
22. AKR1C3 mRNA expression did not differ between bipolar disorder patients in any affective state or in comparison with healthy control subjects. PMID: 25522430
23. A catalysis-independent role for AKR1C3 on AR activity via Siah2 has been identified. PMID: 26160177
24. AKR1C3 mediated doxorubicin resistance might be resulted from the activation of anti-apoptosis PTEN/Akt pathway via PTEN loss. PMID: 25661377
25. Findings indicate the potential involvement of aldo-keto reductase AKR1C3 in the acquired radioresistance by AKR1C3 overexpression. PMID: 25419901
26. Higher expression of PLA2G2A, PTGS2, AKR1B1, AKR1C3 and ABCC4 was seen in 22-B endometriosis cells. PMID: 25446850
27. P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy. PMID: 25514466
28. AKR1C3 2 G allele carriers exhibited greater increases in heart rate and stimulant and sedative effects of alcohol than C allele homozygotes PMID: 24838369
29. Data suggest that reduction of daunorubicin/idarubicin is catalyzed by AKR1C3 and contributes to resistance of carcinoma cells to these anthracyclines; expression of AKR1C3 is induced in carcinoma cells following exposure to daunorubicin/idarubicin. PMID: 24832494
30. AKR1C3 can serve as a promising biomarker for the progression of prostate cancer PMID: 24571686
31. The -71G HSD17B5 variant is not a major component of the molecular pathogenetic mechanisms of PCOS, although it might contribute to the severity of hyperandrogenemia in women with PCOS and biochemical hyperandrogenism. PMID: 18692800
32. 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 PMID: 24244276
33. Report expression of AKR1C3 in neuroendocrine tumors and adenocarcinomas of pancreas, gastrointestinal tract, and lung. PMID: 24228104
34. Silencing of AKR1C3 increases LCN2 expression and inhibits metastasis in cervical cancer. PMID: 24316309
35. Data indicate that fallopian tube and the epithelial component of Brenner tumours (BTs) expressed AKR1C3 and androgen receptor, but the tumour stromal cells showed strong expression of calretinin, inhibin and steroidogenic factor 1 in the majority of BTs. PMID: 24012099
36. Correlation of aldo-ketoreductase (AKR) 1C3 genetic variant with doxorubicin pharmacodynamics in Asian breast cancer patients. PMID: 23116553
37. examine the evidence that supports the vital role of AKR1C3 in CRPC and recent developments in the discovery of potent and selective AKR1C3 inhibitors PMID: 23748150
38. AKR1C3-mediated radioresistance in lung cancer cells is correlated with an arrest in the G2/M cell cycle and a decreased induction of apoptosis. PMID: 23519145
39. The involvement of up-regulated AKR1C1, AKR1C3 and proteasome in CDDP resistance of colon cancers. PMID: 23165153
40. Affect further reduction of 3-keto and 20-keto groups catalyzed by AKR1C2 and AKR1C3. PMID: 23183084
41. AKR1C3 can be considered a therapeutic target in a subgroup of patients with high AKR1C3 expression. PMID: 23196782
42. Our data suggest that there is no association of HSD17B6 and HSD17B5 variants with the occurrence of Polycystic Ovary Syndrome in the Chinese population PMID: 21039282
43. Activin A stimulates AKR1C3 expression and growth in human prostate cancer PMID: 23024260
44. AKR1C3 immunoreactivity was extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction, but not in small cell carcinoma. PMID: 22670171
45. determined the X-ray crystal structure of AKR1C3 with the cofactor NADP+ and the drug-like inhibitor 3-phenoxybenzoic acid bound at a resolution of 1.68 A degrees in space group P212121 PMID: 22505408
46. AKR1C3 functions in differentiation-associated gene regulation and also has a role in supporting inflammation in atopic dermatitis. PMID: 22170488
47. Evidence of association of two alleles for alcohol dependence (AD) is found in SRD5A1 and AKR1C3, mediating a protective effect of the minor allele at each AD marker based on the genotype of the second marker. PMID: 21323680
48. the pro-proliferative action of AKR1C3 in HL-60 cells involves the retinoic acid signalling pathway and that this is in part due to the retinaldehyde reductase activity of AKR1C3 PMID: 21851338
49. role of AKR1C3 in the metabolism of testosterone and progesterone via the 5beta-reductase pathway. PMID: 21521174
50. enhanced metabolism of progesterone by SRD5A1 and the 20alpha-HSD and 3alpha/beta-HSD activities of AKR1C1, AKR1C2 and AKR1C3 PMID: 21232532
51. PTHrP stimulates prostate cancer cell growth and upregulates aldo-keto reductase 1C3 PMID: 21444150
52. AKR1C3 is expressed in both sex hormone-dependent and hormone-independent malignancies. PMID: 21151387
53. These findings suggest that AKR1C3 may play important roles in the physiology of endometrial cells PMID: 20661409
54. AKR1C3 expression occurs in a Tanner stage dependent-fashion. Pre- and peri-pubertal changes appear to promote expression in Leydig cells. The pediatric cryptorchid testis reveals AKR1C3 expression in Sertoli cells PMID: 19942269
55. Expression of AKR1C3 in renal cell carcinoma, papillary urothelial carcinoma, and Wilms tumor is reported. PMID: 20126582
56. A population level survey of AKR1C3 expression in 2,490 individual cases across 19 cancer types using tissue microarrays revealed marked upregulation of AKR1C3 in a subset. PMID: 20145130
57. AKR1C3 expression increased steroid conversion by MCF-7 cells, leading to a pro-estrogenic state. Expression of AKR1C3 also reduced the anti-proliferative effects of PGD(2) on MCF-7 cells. PMID: 20036328
58. Data indicate that enzymes CYP17A1 and HSD3B1 showed low expression, while AKR1C3 and SRD5A1 were abundantly expressed. PMID: 20086173
59. Glaucomatous optic nerve head astrocytes express a higher level of 3 alpha-HSD isoform AKR1C3 and its mRNA than normal astrocytes. PMID: 13678667
60. expression and activity of type 5 17beta-hydroxysteroid dehydrogenase and type 3 3alpha-hydroxysteroid dehydrogenase in female subcutaneous tissue and omental adipose tissue and in preadipocytes PMID: 14671194
61. On the basis of crystal structures, a detailed catalytic mechanism of prostaglandin F synthase is proposed and compared to that of AKR1C1 and AKR1C3. PMID: 14979715
62. Overexpression of hPGFS is associated with primary squamous cell carcinoma of the head and neck and tumour cell lines derived from respiratory and digestive organs PMID: 14997212
63. Expression of SRD5A1 (5alphaR1) and SRD5A2 (5alphaR2) is elevated, and expression of AKR1C1 (20alpha-HSO), AKR1C2 (3alpha-HSO3) and AKR1C3 (3alpha-HSO2) is reduced in tumorous as compared to normal breast tissue. PMID: 15212687
64. Single nucleotide polymorphism may play a role in the pathogenesis of lung cancer in this population, particularly among heavily exposed women. PMID: 15284179
65. enzyme distribution differs between normal and hormonal dependent malignancies of the breast and prostate PMID: 15582534
66. Members of the Sp family of transcription factors play an important role in regulating constitutive and stimulated expression of the HSD17B5 gene in H295R cells. PMID: 15814298
67. AKR1C3 protects the mineralocorticoid receptor from activation by deoxycorticosterone in mineralocorticoid target cells of the kidney and colon. PMID: 16337083
68. The expression of AKR1C1 and AKR1C3 in endometrial cancer will govern the ratio of P:E2. PMID: 16338060
69. Based on model structures & inhibition, catalytic mechanism of PGH2 9,11-endoperoxide reductase of PGFS is proposed.Formation of PGF(2alpha) from PGH2 may involve hydride transfer from bound NADPH to PGH2 endoperoxide without specific amino acid residues. PMID: 16475787
70. Type 5 17beta-HSD (AKR1C3) differs significantly from the type 1 enzyme by possessing a spacious and flexible steroid-binding site. PMID: 16480815
71. Elevated expression of AKR1C3 is highly associated with prostate carcinoma PMID: 16601286
72. Glu77Gly AKR1C3 polymorphism is associated with lower testosterone levels in serum. PMID: 16983398
73. report the clinical history, endocrine evaluation and molecular genetics of a prepubertal girl affected by 17beta-HSD3 deficiency, in whom an erroneous diagnosis of androgen insensitivity syndrome was made PMID: 17071532
74. analysis of human type 5 17beta-hydroxysteroid dehydrogenase conformation and binding to inhibitors PMID: 17166832
75. HSD17B5 single nucleotide polymorphisms predicted to have functional effects do not appear to be a risk factor for precocious pubarche in girls from Barcelona, despite these girls being at high risk of developing androgen excess in adulthood PMID: 17583494
76. Carbonyl reductase-1 (CBR1), microsomal prostaglandin E synthase-1 and 2 (mPGES-1, mPGES-2), cytosolic prostaglandin E synthase (cPGES), aldoketoreductase (AKR1C1) and prostaglandin F synthase (AKR1C3) were all expressed in hair follicles. PMID: 17697149
77. Polymorphisms in the HSD17B5 gene are not associated with risk of polycystic ovary syndrome or elevated testosterone levels. PMID: 17940109
78. The maternal methylenetetrahydrofolate reductase A1298C polymorphism was found to be an effect modifier of the maternal intron 4 polymorphism of the AKR1C3 gene and the childhood leukemia risk. PMID: 18339682
79. Among gene transcripts 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. PMID: 18552976
80. A strong immunoreactivity was detected not only in classically hormone-associated tissues such as prostate and testis but also in non-hormone-associated tissues such as kidney and bladder in humans and rats. PMID: 18574251
81. genetic variation in carcinogen-metabolizing genes, particularly AKR1C3, could be associated with bladder cancer risk. PMID: 18632753
82. Data suggest that adipose tissue AKR1C3 expression may be affected by metabolic disease, and its levels are significantly reduced in response to diet-induced weight loss and correlate with leptin levels. PMID: 18641923
83. Higher mRNA levels of enzymes synthesizing and inactivating androgens are found in differentiated adipocytes, consistent with higher androgen-processing rates in these cells. PMID: 18984855
84. 17beta-HSD type 5 was expressed in 56% of breast cancer specimens. decrease in 17beta-HSD type 5 expressions in breast cancer may play a role in the development &/or progression of cancer by modifying the intratumoral levels of estrogens & androgens. PMID: 18996480
85. This is the first study that addresses whether AKR1C3 mediates carcinogen activation within intact living cells following manipulation of AKR1C3 by molecular intervention. PMID: 19162045
86. By western blot analysis, AKR1C3 is present in human liver obtained at autopsy. By western blot analysis, AKR1C3 is barely detectible in human brain obtained at autopsy. PMID: 19273550
87. AKR1C subfamily genes are stress-inducible and might function as survival factors in keratinocytes. PMID: 19320734
88. AKR1C3, through its ability to convert androstenedione to testosterone, is likely responsible for adrenal testosterone production. PMID: 19336506
89. There is no difference in catalytic properties between variants of 17beta-HSD types 7 and 12 and wild-type enzymes, while variants p.Glu77Gly and p.Lys183Arg in 17beta-HSD type 5 showed a slightly decreased activity. PMID: 19460435
90. AKR1C isoforms as a novel target of jasmonates in cancer cells. PMID: 19487289
91. The researchers found an increased risk of breast cancer in women with AKR1C3 who carried 1 or 2 alleles and who used estrogen-progesterone therapy. PMID: 19846565

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HGNC: 386

OMIM: 603966

KEGG: hsa:8644

STRING: 9606.ENSP00000369927

UniGene: Hs.78183