AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase): Roles in malignancy and endocrine disorders
| Autor: | Trevor M. Penning |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Prostaglandin 030209 endocrinology & metabolism Reductase Endocrine System Diseases Biochemistry Article Epigenesis Genetic 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine Endocrinology Endocrine Gland Neoplasms medicine Humans Prostaglandin-F synthase Enzyme Inhibitors Hydroxysteroid dehydrogenase Aromatase Molecular Biology biology Chemistry Aldo-Keto Reductase Family 1 Member C3 Myeloid leukemia medicine.disease Androgen receptor 030104 developmental biology Cancer research biology.protein Steroids |
| Zdroj: | Mol Cell Endocrinol |
| ISSN: | 0303-7207 |
| Popis: | Aldo-Keto-Reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase (HSD)/prostaglandin (PG) F(2α) synthase) is the only 17β-HSD that is not a short-chain dehydrogenase/reductase. By acting as a 17-ketosteroid reductase, AKR1C3 produces potent androgens in peripheral tissues which activate the androgen receptor (AR) or act as substrates for aromatase. AKR1C3 is implicated in the production of androgens in castration-resistant prostate cancer (CRPC) and polycystic ovarian syndrome; and is implicated in the production of aromatase substrates in breast cancer. By acting as an 11-ketoprostaglandin reductase, AKR1C3 generates 11β-PGb(2α) to activate the FP receptor and deprives peroxisome proliferator activator receptorγ of its putative PGJ(2) ligands. These growth stimulatory signals implicate AKR1C3 in non-hormonal dependent malignancies e.g. acute myeloid leukemia (AML). AKR1C3 moonlights by acting as a co-activator of the AR and stabilizes ubiquitin ligases. AKR1C3 inhibitors have been used clinically for CRPC and AML and can be used to probe its pluripotency. |
| Databáze: | OpenAIRE |
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