Volume 9, Issue 5 (September 2007) 9, 601–609; 10.1111/j.1745-7262.2007.00328.x
Ectopic expression of neurotrophic peptide derived from saposin C increases proliferation and upregulates androgen receptor expression and transcriptional activity in human prostate cancer cells
Yan Ding, Hui-Qing Yuan, Feng Kong, Xiao-Yan Hu, Kai Ren, Jie Cai, Xiao-Ling Wang and Charles Y F Young
1.Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, China 2.Departments of Urology and Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA
Correspondence: Dr Hui-Qing Yuan, Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Wenhua West Road 44, Jinan 250012, China. Fax: +86-531-8838-2019. E-mail: lyuanhq@sdu.edu.cn
Received 9 January 2007; Accepted 6 June 2007.
Abstract |
Aim: To determine the effects of the functional domain of saposin C (neurotrophic peptide [NP]) on androgen receptor (AR) expression and transcriptional activity.
Methods: We constructed DNA vectors expressing NP or a chimeric peptide of the viral TAT transduction domain and NP (TAT-NP) using gene cloning technology. The effects of ectopic expression of NP or TAT-NP on cell growth were examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, transient transfection and reporter gene assays were used to determine the effects of NP on AR expression and activation.
Results: NP stimulated proliferation of androgen responsive LNCaP cells in the absence of androgens. RT-PCR and Western blot analyses showed that ectopic expression of NP resulted in induction of AR gene expression, and that the NP-stimulated expression of AR could be synergistically enhanced in the presence of androgens. Furthermore, reporter gene assay results showed that NP could enhance AR transactivation by increasing androgen-inducible gene reporter activity.
Conclusion: We provided evidence that ectopic expression of saposin C-originated NP could upregulate AR gene expression and activate the AR transcriptional function in an androgen-independent manner in prostate cancer cells.
Keywords: neurotrophic peptide, androgen receptor, saposin C, prostate carcinoma cell lines
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