标题：Associations of saposin C, Src, and androgen receptor upregulate the expression and function of androgen receptor in human prostate cancer cells.
作者：Ding Y;Wang X;Xu A;Xu X;Tian K;Young CY;Yuan H
作者机构：[Ding, Y] Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China, School of 更多
通讯作者地址：[Yuan, HQ]Shandong Univ, Sch Med, Dept Biochem & Mol Biol, 44 Wenhua Xi Rd, Jinan 250012, Peoples R China.
来源：Journal of Cellular Biochemistry
关键词：SAPOSIN C; ANDROGEN RECEPTOR; SRC; PROSTATE CARCINOMA CELLS
摘要：We previously demonstrated that ectopic expression of neurotrophic peptide (NP) derived from saposin C promotes androgen receptor (AR) expression and transactivation in human prostate cancer cells. This prompted us to investigate how NP or saposin C can function in cells. We constructed plasmids expressing saposin C or a chimeric peptide of a viral TAT transduction domain and saposin C (TAT-saposin C) with His-tag. Intracellular localization of saposin C and NP was predominantly shown in transfected cells, while TAT-saposin C was detected around membrane and in cytosol by immunofluorescence staining. Furthermore, induction of the AR expression and activation of the AR transcriptional function were observed in cells transfected with saposin C or TAT-saposin C, compared to control cells transfected with an empty plasmid. The effects of saposin C and TAT-saposin C on AR activity were examined in the presence of inhibitors of GPCR, MAPK1/2, and PI3K/Akt. Interestingly, we found that these inhibitors only affect AR activities in cells with TAT-saposin C expression but not with saposin C expression. Immunostaining images showed that co-localization of saposin C, Src, and the AR occurred in transfected cells. Physical interactions of saposin C/NP, Src, and the AR were then demonstrated by co-immunoprecipitation assays. Blockage of Src activity by specific inhibitor led to a decrease in the saposin C-mediated enhancement of AR transactivity, suggesting that intracellular expression of saposin C caused stimulation of AR expression and activity by associations with Src in LNCaP cells. This effect may not be mediated by GPCR.