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Prosaposin upregulates AR and PSA expression and activity in prostate cancer cells (LNCaP)
Author(s) -
Koochekpour Shahriar,
Lee TaeJin,
Wang Ruoxiang,
Culig Zoran,
Delorme Nathalie,
Caffey Soren,
Marrero Luis,
Aguirre Jennifer
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20513
Subject(s) - lncap , androgen receptor , prostate cancer , bicalutamide , signal transduction , transfection , cancer research , androgen , biology , reporter gene , protein kinase b , endocrinology , medicine , microbiology and biotechnology , gene expression , cell culture , cancer , gene , biochemistry , hormone , genetics
BACKGROUND Prosaposin overexpression and/or genomic amplification have been demonstrated in androgen‐independent (AI) prostate cancer cell lines and tissues. Here, we explored the possibility for a functional relationship between prosaposin and androgen receptor (AR) in LNCaP cells. METHODS The effect of prosaposin or its active molecular derivatives (e.g., saposin C) on expression and activity of androgen receptor (AR) and prostate‐specific antigen (PSA) was examined by using immunoblotting, RT‐PCR, transfection, and reporter gene assays, immunofluorescence staining, and inhibitors of signal transduction pathways. RESULTS Prosaposin or saposin C, in an AI‐manner, (a) increased AR mRNA and protein expression and nuclear AR content and its phosphorylation state; (b) increased PSA mRNA and protein expression; and (c) upregulated PSA‐ and an androgen‐inducible probasin (PB)‐reporter gene activity in LNCaP and AR‐transfected PC‐3 cells. Induction of PSA expression and reporter activity was substantially blocked or prevented with the antiandrogen bicalutamide, pertussis toxin, or inhibitors of MAPK‐ and PI3K/Akt‐signaling pathways, indicating an androgen‐agonistic effect for saposin C that involves AR and multiple signaling pathways. CONCLUSIONS The results for the first time introduce prosaposin as an androgen‐agonist in prostate cancer cells. This finding, together with the growth‐promoting effect and overexpression of prosaposin, may support a growth advantage to AI prostate cancer cells. Prostate © 2006 Wiley‐Liss, Inc.