Melatonin elicits nuclear exclusion of the human androgen receptor and attenuates its activity
| Autor: | Zippora Lupowitz, Zoran Culig, Georg Bartsch, Nava Zisapel, Galit Levy-Rimler, Avi Rimler, Helmut Klocker, Haim Matzkin |
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| Rok vydání: | 2001 |
| Předmět: |
Agonist
Male medicine.medical_specialty medicine.drug_class Urology Blotting Western Biology Transfection Melatonin Prostate cancer Internal medicine LNCaP medicine Androgen Receptor Antagonists Tumor Cells Cultured Humans Nandrolone RNA Messenger Cell Nucleus Reverse Transcriptase Polymerase Chain Reaction Prostatic Neoplasms Androgen medicine.disease Immunohistochemistry Androgen receptor Endocrinology Oncology Receptors Androgen Dihydrotestosterone Cancer research medicine.drug |
| Zdroj: | The Prostate. 49(2) |
| ISSN: | 0270-4137 |
| Popis: | Background The androgen receptor (AR) promotes growth and functionality of androgen sensitive benign and cancer tissues. The pineal hormone melatonin is an androgen protagonist in vivo and in vitro. The interference of melatonin in the AR cascade was explored. Methods The effects of melatonin on AR expression, level, agonist and androgen-response element (ARE) binding, reporter gene activity and intracellular localization were explored in prostate cancer LNCaP cell line. Results Melatonin increased immunoreactive AR cells in the absence and presence of dihydrotestosterone. Despite this increase and maintenance of AR agonist binding capacity, the androgen-induced reporter gene activity and suppression of AR-mRNA were attenuated. Immunocytochemical analysis and subcellular fractionation studies revealed nuclear exclusion of AR by melatonin. Conclusions The melatonin-mediated nuclear exclusion of the AR may explain the attenuation of AR activity in the prostate cancer cells. This is the first demonstration of a hormone-induced mislocalization of the AR in prostate epithelial cells and may represent a novel route for regulating AR activity. Prostate 49:145–154, 2001. © 2001 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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