Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP.

Abstract:

:Androgen-regulated genes (ARG) are implicated in normal and neoplastic growth of the prostate. Recently, we reported genomic amplification and/or overexpression of a previously known neurotrophic factor, prosaposin, in androgen-independent (AI) or metastatic prostate cancer (PCa) cells and tissues. Prosaposin and/or its known active molecular derivatives (e.g., saposin C) function as a pluripotent growth factor with diverse biological activities that favor malignant phenotypes in PCa cells. In addition, prosaposin or saposin C upregulates androgen receptor (AR) and AR-target genes (i.e., prostate-specific antigen, Probasin) expression and activity in LNCaP cells. Here, we examined prosaposin as an ARG. We report that DHT treatment of LNCaP cells increases prosaposin expression. In addition, we demonstrate androgen-responsiveness of prosaposin promoter and AR occupancy to a hormone-responsive element located in the proximal region of the prosaposin promoter. Our data for the first time identify prosaposin as an ARG. This observation, together with the pleiotropic growth factor activity of prosaposin, might suggest a role for this molecule in AR-dependent progression of prostate cancer at its early or late AI-state.

journal_name

J Cell Biochem

authors

Koochekpour S,Lee TJ,Wang R,Sun Y,Delorme N,Hiraiwa M,Grabowski GA,Culig Z,Minokadeh A

doi

10.1002/jcb.21207

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

631-41

issue

3

eissn

0730-2312

issn

1097-4644

journal_volume

101

pub_type

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