Transforming growth factor β1 increase of hydroxysteroid dehydrogenase proteins is partly suppressed by red clover isoflavones in human primary prostate cancer-derived stromal cells
| Autor: | Xunxian Liu, Julia T. Arnold, Yun-Shang Piao |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
endocrine system Cancer Research medicine.medical_specialty Cell type 3-Hydroxysteroid Dehydrogenases animal structures Stromal cell Immunoblotting Cell Biology Real-Time Polymerase Chain Reaction Estradiol Dehydrogenases Transforming Growth Factor beta1 Downregulation and upregulation Internal medicine medicine Humans Immunoprecipitation Testosterone Hydroxysteroid dehydrogenase Receptor Cells Cultured Cancer Biology Aldo-Keto Reductase Family 1 Member C3 Hydroxysteroid Dehydrogenases Prostate Prostatic Neoplasms General Medicine Prostate-Specific Antigen Isoflavones medicine.anatomical_structure Endocrinology Hydroxyprostaglandin Dehydrogenases Trifolium Stromal Cells Signal transduction Receptors Transforming Growth Factor beta Transforming growth factor |
| Zdroj: | Carcinogenesis. 32:1648-1654 |
| ISSN: | 1460-2180 0143-3334 |
| Popis: | Transforming growth factor β1 (TGF-β1) increases dehydro-epiandrosterone (DHEA) metabolism to androgens and prostate-specific antigen (PSA) in a prostate tissue model where stromal (6S) cells and epithelial (LAPC-4) cells are cocultured. Red clover (RC) isoflavones inhibits transforming growth factor (TGF)-β-induced androgenicity. Mechanisms controlling those activities were explored. Three hydroxysteroid dehydrogenases (HSDs), 3β-HSD, HSD-17β1 and HSD-17β5 involved in metabolizing DHEA to testosterone (TESTO) were investigated. Individual depletion of HSDs in 6S cells significantly reduced TGF-β1/DHEA-induced PSA in LAPC-4 cells in cocultures. Monomer amounts of 3β-HSD were similar without or with TGF-β1 in both cell types but aggregates of 3β-HSD in 6S cells were much higher than those in LAPC-4 cells and were upregulated by TGFβ in 6S cells. Basal and TGF-β1-treated levels of HSD-17β1 and HSD-17β5 in LAPC-4 cells were significantly lower than in 6S cells, whereas levels of HSD-17β1 but not HSD-17β5 were TGFβ inducible. 6S cell HSD genes expression induced by TGFβ or androgen signaling was insignificant to contribute TGF-β1/DHEA-upregulated protein levels of HSDs. RC decreased TGF-β1- upregulation of aggregates of 3β-HSD but not HSD-17β1. Depletion of TGFβ receptors (TGFβ Rs) reduced TGF-β1/DHEA-upregulated HSDs and TESTO. Immunoprecipitation studies demonstrated that TGF-β1 disrupted associations of TGFβ Rs/HSDs aggregates, whereas RC suppressed the dissociations of aggregates of 3β-HSD but not HSD-17β1 from the receptors. Given that TGFβ Rs are recycled with or without ligand, TGF-β1-induced disassociation of the HSDs from TGFβ Rs may increase stability and activity of the HSDs. These data suggest a pathway connecting overproduction of TGFβ with increased PSA in prostate cancer. |
| Databáze: | OpenAIRE |
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