The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells
| Autor: | Maryam Ghotbaddini, Joann B. Powell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty endocrine system Polychlorinated Dibenzodioxins Transcription Genetic medicine.drug_class Health Toxicology and Mutagenesis lcsh:Medicine Ligands Article 03 medical and health sciences Prostate cancer 0302 clinical medicine Internal medicine Cell Line Tumor androgen receptor LNCaP TCDD/dioxin medicine Cytochrome P-450 CYP1A1 Humans heterocyclic compounds Castration reproductive and urinary physiology 030304 developmental biology 0303 health sciences biology Chemistry AhR lcsh:R Public Health Environmental and Occupational Health Prostatic Neoplasms medicine.disease Androgen Aryl hydrocarbon receptor prostate cancer Androgen receptor stomatognathic diseases Endocrinology Receptors Aryl Hydrocarbon Hormone receptor Receptors Androgen 030220 oncology & carcinogenesis Cancer cell biology.protein Tumor promotion castration-resistant Signal Transduction |
| Zdroj: | International Journal of Environmental Research and Public Health, Vol 12, Iss 7, Pp 7506-7518 (2015) International Journal of Environmental Research and Public Health Volume 12 Issue 7 Pages 7506-7518 |
| ISSN: | 1660-4601 |
| Popis: | The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR). TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR) expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models. |
| Databáze: | OpenAIRE |
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