AKR1C3 (aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II))
2007-11-01 Hsueh Kung Lin AffiliationDepartment of Urology, University of Oklahoma Health Sciences Center, 920 Stanton L Young Blvd, WP3150, Oklahoma City, Oklahoma 73104, USA
Identity
HGNC
LOCATION
10p15.1
LOCUSID
ALIAS
DD3,DDX,HA1753,HAKRB,HAKRe,HSD17B5,PGFS,hluPGFS
FUSION GENES
DNA/RNA
Transcription
1170 bp mRNA; transcript has been detected in brain, lung, liver, small intestine, mammary gland, uterus, prostate, testis.
Proteins
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.
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
Entity name
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 name
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 name
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 name
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16735089 | 2006 | Paracrine-stimulated gene expression profile favors estradiol production in breast tumors. | Amin SA et al |
| 12543809 | 2003 | 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 et al |
| 10067877 | 1999 | 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 et al |
| 16601286 | 2006 | 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 et al |
| 15492289 | 2004 | Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling. | Ji Q et al |
| 15212687 | 2004 | Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma. | Lewis MJ et al |
| 9415401 | 1997 | 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 et al |
| 16838325 | 2006 | Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemia. | Mahadevan D et al |
| 15788642 | 2005 | In situ androgen producing enzymes in human prostate cancer. | Nakamura Y et al |
| 11174850 | 2001 | Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in the human prostate and mammary gland. | Pelletier G et al |
| 16417966 | 2006 | Aldo-keto reductase (AKR) 1C3: role in prostate disease and the development of specific inhibitors. | Penning TM et al |
| 16338060 | 2006 | AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer. | Rizner TL et al |
| 16510604 | 2006 | Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. | Stanbrough M et al |
Other Information
Locus ID:
NCBI: 8644
MIM: 603966
HGNC: 386
Ensembl: ENSG00000196139
Variants:
dbSNP: 8644
ClinVar: 8644
TCGA: ENSG00000196139
COSMIC: AKR1C3
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000196139 | ENST00000380554 | P42330 |
| ENSG00000196139 | ENST00000439082 | A0A0A0MSS8 |
| ENSG00000196139 | ENST00000602997 | S4R3D5 |
| ENSG00000196139 | ENST00000605149 | S4R3Z2 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA443560 | Breast Neoplasms | Disease | ClinicalAnnotation | associated | 23116553 | ||
| PA449212 | daunorubicin | Chemical | VariantAnnotation | associated | PK | 20837989 | |
| PA449383 | docetaxel | Chemical | ClinicalAnnotation | associated | 23116553 | ||
| PA449412 | doxorubicin | Chemical | ClinicalAnnotation, Pathway, VariantAnnotation | associated | PK | 20837989, 21048526, 23116553 | |
| PA449563 | exemestane | Chemical | ClinicalAnnotation | associated | PK | 27111237 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38122923 | 2024 | Inhibition of aldo-keto reductase 1C3 overcomes gemcitabine/cisplatin resistance in bladder cancer. | 2 |
| 38349266 | 2024 | AKR1C3 silencing inhibits autophagy-dependent glycolysis in thyroid cancer cells by inactivating ERK signaling. | 0 |
| 38122923 | 2024 | Inhibition of aldo-keto reductase 1C3 overcomes gemcitabine/cisplatin resistance in bladder cancer. | 2 |
| 38349266 | 2024 | AKR1C3 silencing inhibits autophagy-dependent glycolysis in thyroid cancer cells by inactivating ERK signaling. | 0 |
| 36413758 | 2023 | Availability of aldo-keto reductase 1C3 and ATP-binding cassette B1 as therapeutic targets for alleviating paclitaxel resistance in breast cancer MCF7 cells. | 1 |
| 36841845 | 2023 | Influence of aldo-keto reductase 1C3 polymorphisms in early-onset female psoriasis patients. | 0 |
| 36901944 | 2023 | Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer. | 4 |
| 36920042 | 2023 | AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway. | 7 |
| 37344179 | 2023 | In Vitro Evaluation of the Reductase Activities of Human AKR1C3 Allelic Variants. | 1 |
| 38003379 | 2023 | Keratinocytes Exposed to Blue or Red Light: Proteomic Characterization Showed Cytoplasmic Thioredoxin Reductase 1 and Aldo-Keto Reductase Family 1 Member C3 Triggered Expression. | 1 |
| 38188684 | 2023 | Aldo-keto reductase family member C3 (AKR1C3) promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α. | 1 |
| 36413758 | 2023 | Availability of aldo-keto reductase 1C3 and ATP-binding cassette B1 as therapeutic targets for alleviating paclitaxel resistance in breast cancer MCF7 cells. | 1 |
| 36841845 | 2023 | Influence of aldo-keto reductase 1C3 polymorphisms in early-onset female psoriasis patients. | 0 |
| 36901944 | 2023 | Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer. | 4 |
| 36920042 | 2023 | AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway. | 7 |
Citation
Hsueh Kung Lin
AKR1C3 (aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II))
Atlas Genet Cytogenet Oncol Haematol. 2007-11-01
Online version: http://atlasgeneticsoncology.org/gene/612/akr1c3
