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AKR1C3 (aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II))

Written2007-11Hsueh Kung Lin
Department of Urology, University of Oklahoma Health Sciences Center, 920 Stanton L Young Blvd, WP3150, Oklahoma City, Oklahoma 73104, USA

(Note : for Links provided by Atlas : click)

Identity

Other aliasDD3
HA1753
HAKRB
HAKRe
HSD17B5
KIAA0119
hluPGFS
LocusID (NCBI) 8644
Atlas_Id 612
Location 10p15.1  [Link to chromosome band 10p15]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AKR1C3 (10p15.1) / CLSTN1 (1p36.22)

DNA/RNA

Transcription 1170 bp mRNA; transcript has been detected in brain, lung, liver, small intestine, mammary gland, uterus, prostate, testis.

Protein

Description 323 amino acids, molecular weight 37 kDa.
Expression Activated macrophage, malignant prostate epithelium, normal mammary epithelium, mature blood vessel.
Localisation Mainly in cytoplasm.
Function AKR1C3 metabolizes various androgen metabolites including 5a-dihydrotestosterone to 5a-androstane-3a,17b-diol, Delta4-androstene-3,17-dione to testosterone, androstanedione to 5a-dihydrotestosterone, androsterone to 5a-androstane-3a,17b-diol.
AKR1C3 is also involved in estrogen metabolism converting estrone to 17b-estradiol as well as progesterone metabolism converting prostaglandin D2 to 9a,11b-prostaglandin F2a.
AKR1C3 has the capability of regulating the trans-activation of various nuclear receptors including androgen receptor, estrogen receptor, and peroxisome proliferator activated receptor (PPARG) by regulating the ligand availability for the nuclear receptors.
Homology A member of the of AKR1C family proteins; AKR1C1, AKR1C2, AKR1C3, AKR1C4 in human, and AKR1C9 in rat.

Mutations

Note Mutation of AKR1C3 has not been identified.

Implicated in

Note
  
Entity Various cancers
Note Elevated levels of AKR1C3 expression are implicated in leukemia cell differentiation, prostate cancer (in both androgen-dependent and androgen-independent prostate cancer), and endometrial cancer. Expression of AKR1C3 was detected in a patient with myelodysplastic syndrome (MDS, refractory anemia) with progression to acute myelogenous leukemia. Overexpression of AKR1C3 in a human promyelocytic leukemia cell line, HL-60, rendered cells more resistant to all-trans retinoic acid (ATRA) and 1a,25-dihydroxyvitamin D3 induced cell differentiation.
  
  
Entity Prostate cancer
Disease Immunohistochemical staining of human prostate tissues detected negative or low levels of AKR1C3 expression in normal prostate epithelial cells. Strong positive AKR1C3 immunoreactivity was demonstrated in primary and androgen-independent prostate cancers. Variable increases in AKR1C3 expression were also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy, and urothelial cell metaplasia.
  
  
Entity Endometrial cancer
Disease Quantitative transcriptosome analysis using real-time polymerase chain reaction, AKR1C3 mRNA expression was shown to be elevated in endometrial cancer versus adjacent normal endometrium.
  
  
Entity Breast tumor
Disease Expression of AKR1C3 mRNA was reduced in breast tumor as compared to adjacent normal breast tissue. Immunohistochemstry revealed that the ductal epithelial cells and stromal cells of the breast express AKR1C3. In myoepithelial cells of the breast, immunoreactive AKR1C3 was absent in normal tissues, whereas strong AKR1C3 staining was apparent in cells surrounding the neoplastic epithelium of ductal carcinoma in situ.
  

Bibliography

Paracrine-stimulated gene expression profile favors estradiol production in breast tumors.
Amin SA, Huang CC, Reierstad S, Lin Z, Arbieva Z, Wiley E, Saborian H, Haynes B, Cotterill H, Dowsett M, Bulun SE
Molecular and cellular endocrinology. 2006 ; 253 (1-2) : 44-55.
PMID 16735089
 
The aldo-keto reductase AKR1C3 is a novel suppressor of cell differentiation that provides a plausible target for the non-cyclooxygenase-dependent antineoplastic actions of nonsteroidal anti-inflammatory drugs.
Desmond JC, Mountford JC, Drayson MT, Walker EA, Hewison M, Ride JP, Luong QT, Hayden RE, Vanin EF, Bunce CM
Cancer research. 2003 ; 63 (2) : 505-512.
PMID 12543809
 
Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the human prostate by in situ hybridization and immunocytochemistry.
El-Alfy M, Luu-The V, Huang XF, Berger L, Labrie F, Pelletier G
Endocrinology. 1999 ; 140 (3) : 1481-1491.
PMID 10067877
 
Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma.
Fung KM, Samara EN, Wong C, Metwalli A, Krlin R, Bane B, Liu CZ, Yang JT, Pitha JV, Culkin DJ, Kropp BP, Penning TM, Lin HK
Endocrine-related cancer. 2006 ; 13 (1) : 169-180.
PMID 16601286
 
Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling.
Ji Q, Aoyama C, Nien YD, Liu PI, Chen PK, Chang L, Stanczyk FZ, Stolz A
Cancer research. 2004 ; 64 (20) : 7610-7617.
PMID 15492289
 
Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma.
Lewis MJ, Wiebe JP, Heathcote JG
BMC cancer. 2004 ; 4 : page 27.
PMID 15212687
 
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.
Lin HK, Jez JM, Schlegel BP, Peehl DM, Pachter JA, Penning TM
Molecular endocrinology (Baltimore, Md.). 1997 ; 11 (13) : 1971-1984.
PMID 9415401
 
Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemia.
Mahadevan D, DiMento J, Croce KD, Riley C, George B, Fuchs D, Mathews T, Wilson C, Lobell M
American journal of hematology. 2006 ; 81 (10) : 779-786.
PMID 16838325
 
In situ androgen producing enzymes in human prostate cancer.
Nakamura Y, Suzuki T, Nakabayashi M, Endoh M, Sakamoto K, Mikami Y, Moriya T, Ito A, Takahashi S, Yamada S, Arai Y, Sasano H
Endocrine-related cancer. 2005 ; 12 (1) : 101-107.
PMID 15788642
 
Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in the human prostate and mammary gland.
Pelletier G, Luu-The V, El-Alfy M, Li S, Labrie F
Journal of molecular endocrinology. 2001 ; 26 (1) : 11-19.
PMID 11174850
 
Aldo-keto reductase (AKR) 1C3: role in prostate disease and the development of specific inhibitors.
Penning TM, Steckelbroeck S, Bauman DR, Miller MW, Jin Y, Peehl DM, Fung KM, Lin HK
Molecular and cellular endocrinology. 2006 ; 248 (1-2) : 182-191.
PMID 16417966
 
AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer.
Rizner TL, Smuc T, Rupreht R, Sinkovec J, Penning TM
Molecular and cellular endocrinology. 2006 ; 248 (1-2) : 126-135.
PMID 16338060
 
Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer.
Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP
Cancer research. 2006 ; 66 (5) : 2815-2825.
PMID 16510604
 

Citation

This paper should be referenced as such :
Lin, HK
AKR1C3 (aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II))
Atlas Genet Cytogenet Oncol Haematol. 2008;12(4):267-268.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/AKR1C3ID612ch10p15.html


External links

Nomenclature
Cards
AtlasAKR1C3ID612ch10p15.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)8644
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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