Ectopic expression of neurotrophic peptide derived from saposin C increases proliferation and upregulates androgen receptor expression and transcriptional activity in human prostate cancer cells / 亚洲男科学杂志(英文版)

ABSTRACT

<p><b>AIM</b>To determine the effects of the functional domain of saposin C (neurotrophic peptide [NP]) on androgen receptor (AR) expression and transcriptional activity.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>