Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP.
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.
Koochekpour
S
S
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA. skooch@lsuhsc.edu
Lee
T-J
TJ
Wang
R
R
Sun
Y
Y
Delorme
N
N
Hiraiwa
M
M
Grabowski
G A
GA
Culig
Z
Z
Minokadeh
A
A
D000728:Androgens / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D013196:Dihydrotestosterone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049231:Saposins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
C410798:AR protein, human; D000728:Androgens; D015850:Interleukin-6; C483345:PSAP protein, human; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D049231:Saposins; D013196:Dihydrotestosterone; D007334:Insulin-Like Growth Factor I; D008156:Luciferases