Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth

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• 作者：Claire Martin ; Jean-Michel Lafosse ; Bernard Malavaud ; Olivier Cuvillier
• 关键词：Osteoblasts ; Androgens ; Sphingosine kinase-1 ; ERK1/2 ; PI3K
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2010
• 出版时间：1 January 2010
• 年：2010
• 卷：391
• 期：1
• 页码：669-673
• 全文大小：572 K

文摘

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.