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Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth

Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts. Dihydrotestosterone (DHT) triggered cell growth in steroid-deprived MC3T3 cells, which was associated with a rapid stimulation of SphK1 and activation...

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Published in:	Biochemical and biophysical research communications 2010-01, Vol.391 (1), p.669-673
Main Authors:	Martin, Claire, Lafosse, Jean-Michel, Malavaud, Bernard, Cuvillier, Olivier
Format:	Article
Language:	English
Subjects:	60 APPLIED LIFE SCIENCES ANDROGENS Androgens - metabolism Androgens - pharmacology ANIMAL GROWTH Animals Cell Line CELL PROLIFERATION CHARCOAL CONNECTIVE TISSUE CELLS Dihydrotestosterone - metabolism Dihydrotestosterone - pharmacology ERK1/2 INHIBITION LIPIDS Mice Osteoblasts Osteoblasts - drug effects Osteoblasts - enzymology Osteoblasts - physiology Phosphatidylinositol 3-Kinases - metabolism Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors Phosphotransferases (Alcohol Group Acceptor) - metabolism PI3K Proto-Oncogene Proteins c-akt - metabolism RECEPTORS Receptors, Androgen - metabolism SIGNALS Sphingosine kinase-1 STIMULATION
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container_title	Biochemical and biophysical research communications
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creator	Martin, Claire Lafosse, Jean-Michel Malavaud, Bernard Cuvillier, Olivier
description	Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts. Dihydrotestosterone (DHT) triggered cell growth in steroid-deprived MC3T3 cells, which was associated with a rapid stimulation of SphK1 and activation of both Akt and ERK signaling pathways. This mechanism relied on functional androgen receptor/PI3K/Akt nongenotropic signaling as pharmacological antagonists could block SphK1 stimulation by DHT and its consequences. Finally, SphK1 inhibition not only abrogated DHT-induced ERK activation but also blocked cell proliferation, while ERK inhibition had no impact, suggesting that SphK1 was critical for DHT signaling yet independently of the ERK.
doi_str_mv	10.1016/j.bbrc.2009.11.118
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subjects	60 APPLIED LIFE SCIENCES ANDROGENS Androgens - metabolism Androgens - pharmacology ANIMAL GROWTH Animals Cell Line CELL PROLIFERATION CHARCOAL CONNECTIVE TISSUE CELLS Dihydrotestosterone - metabolism Dihydrotestosterone - pharmacology ERK1/2 INHIBITION LIPIDS Mice Osteoblasts Osteoblasts - drug effects Osteoblasts - enzymology Osteoblasts - physiology Phosphatidylinositol 3-Kinases - metabolism Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors Phosphotransferases (Alcohol Group Acceptor) - metabolism PI3K Proto-Oncogene Proteins c-akt - metabolism RECEPTORS Receptors, Androgen - metabolism SIGNALS Sphingosine kinase-1 STIMULATION
title	Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth
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