TY - JOUR
T1 - Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death
AU - Kaushik, Maiti
AU - Oh, Dayoung
AU - Jung, Sun Moon
AU - Sujata, Acharjee
AU - Jian, Hua Li
AU - Dong, Gyu Bai
AU - Hee-Sae, Park
AU - Keesook, Lee
AU - Young, Chul Lee
AU - Neon, Chul Jung
AU - Kyungjin, Kim
AU - Hubert, Vaudry
AU - Hyuk, Bang Kwon
AU - Jae, Young Seong
PY - 2005/7
Y1 - 2005/7
N2 - 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 Ca 2+ from internal Ca2+ stores. Interestingly, the [Ca 2+]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.
AB - 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 Ca 2+ from internal Ca2+ stores. Interestingly, the [Ca 2+]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.
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U2 - 10.1210/jc.2004-1894
DO - 10.1210/jc.2004-1894
M3 - Article
C2 - 15870130
AN - SCOPUS:23044486562
SN - 0021-972X
VL - 90
SP - 4287
EP - 4298
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 7
ER -