Prostate-derived factor as a paracrine and autocrine factor for the proliferation of androgen receptor-positive human prostate cancer cells.
BACKGROUND
The expression of prostate-derived factor (PDF) is significantly elevated in human prostate tumors. We investigate the functional role and signaling of PDF in androgen receptor (AR)-positive human prostate cancer cells.


METHODS
Transient or stable expression of PDF by cDNA transfection, antisense-mediated gene silencing, media conditioned by PDF-elevated cells, and antibody (Ab) neutralization were employed.


RESULTS
Elevated endogenous and exogenous expression of PDF and treatment of PDF-enriched media were associated with increased proliferation and clonogenic growth of the cells. On the contrary, knockdown of PDF or addition of PDF neutralizing Ab resulted in diminished proliferation and reduced anchorage-independent growth. Further, ERK1/2 and p90RSK, but not Smad2/3, were activated in PDF-elevated cells as well as in cells treated with PDF-enriched media, while inhibition of ERK1/2 decreased the growth of those cells.


CONCLUSIONS
PDF promotes AR-positive prostate tumor progression through upregulating cell proliferation via ERK1/2 signal pathway.
Chen
Siu-Ju
SJ
Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Karan
Dev
D
Johansson
Sonny L
SL
Lin
Fen-Fen
FF
Zeckser
Jeffrey
J
Singh
Ajay P
AP
Batra
Surinder K
SK
Lin
Ming-Fong
MF
D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D020868:Gene Silencing; D055436:Growth Differentiation Factor 15; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000096:biosynthesis*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
C410798:AR protein, human; D019485:Bone Morphogenetic Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D011944:Receptors, Androgen; D016212:Transforming Growth Factor beta; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3