Differential Effects of Gonadotropin-Releasing Hormone (GnRH)-I and GnRH-II on Prostate Cancer Cell Signaling and Death
| Autor: | Young Chul Lee, Hubert Vaudry, Hyuk Bang Kwon, Sujata Acharjee, Neon Chul Jung, Hee-Sae Park, Keesook Lee, Da Young Oh, Dong Gyu Bai, Jae Young Seong, Kyungjin Kim, Jian Hua Li, Jung Sun Moon, Kaushik Maiti |
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| Rok vydání: | 2005 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Inositol Phosphates Endocrinology Diabetes and Metabolism Clinical Biochemistry Apoptosis Photoaffinity Labels Gonadotropin-releasing hormone Biology Biochemistry Gonadotropin-Releasing Hormone Endocrinology Internal medicine medicine Humans Reverse Transcriptase Polymerase Chain Reaction Ryanodine receptor Biochemistry (medical) Antagonist Prostatic Neoplasms Ryanodine Receptor Calcium Release Channel Inositol trisphosphate receptor Mechanism of action Calcium medicine.symptom Signal transduction Receptors LHRH hormones hormone substitutes and hormone antagonists Intracellular Signal Transduction |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 90:4287-4298 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2004-1894 |
| Popis: | Context: GnRH is known to directly regulate prostate cancer cell proliferation, but the precise mechanism of action of the peptide is still under investigation.Objective: This study demonstrates differential effects of GnRH-I and GnRH-II on androgen-independent human prostate cancer cells.Results: Both GnRH-I and GnRH-II increased the intracellular Ca2+ concentration ([Ca2+]i) either through Ca2+ influx from external Ca2+ source or via mobilization of Ca2+ from internal Ca2+ stores. Interestingly, the [Ca2+]i increase was mediated by activation of the ryanodine receptor but not the inositol trisphosphate receptor. Trptorelix-1, a novel GnRH-II antagonist but not cetrorelix, a classical GnRH-I antagonist, completely inhibited the GnRH-II-induced [Ca2+]i increase. Concurrently at high concentrations, trptorelix-1 and cetrorelix inhibited GnRH-I-induced [Ca2+]i increase, whereas at low concentrations they exerted an agonistic action, inducing Ca2+ influx. High concentrations of trptorelix-1 but not cetrorelix-induced prostate cancer cell death, probably through an apoptotic process. Using photoaffinity labeling with 125I-[azidobenzoyl-d-Lys6]GnRH-II, we observed that an 80-kDa protein specifically bound to GnRH-II.Conclusions: This study suggests the existence of a novel GnRH-II binding protein, in addition to a conventional GnRH-I receptor, in prostate cancer cells. These data may facilitate the development of innovatory therapeutic drugs for the treatment of prostate cancer. |
| Databáze: | OpenAIRE |
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