Proprotein convertases regulate activity of prostate epithelial cell differentiation markers and are modulated in human prostate cancer cells.
Prostate derived factor (PDF) is a member of transforming growth factor-beta (TGF-beta) superfamily proteins involved in differentiation of the prostate epithelium. Proprotein convertases (PCs) such as furin are thought to mediate the processing of TGF-beta superfamily. In the present study, we demonstrated for the first time that human prostate cancer cell lines differentially synthesize and secret prostate derived factor (PDF), and that PDF secreted by LNCaP is processed by PCs. Exposure of LNCaP cells to the decanoyl-Arg-Val-Lys-Arg-chloromethylketone (CMK), a synthetic furin-like protease inhibitor, inhibited PDF processing and resulted in the loss of luminal cell phenotype and induction of basal cell phenotype in LNCaP cells as demonstrated by alternations in the expression of cytokeratins 8, 14, 18, and 19, markers of prostate epithelial cell differentiation. These results suggest that proprotein convertases may be involved in the regulation of prostate epithelial cell differentiation, and may be an important target of prostate cancer therapy.
Uchida
Katsunori
K
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63100, USA.
Chaudhary
Lala R
LR
Sugimura
Yoshiki
Y
Adkisson
Huston D
HD
Hruska
Keith A
KA
D000943:Antigens, Differentiation / Q000378:metabolism*; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins; D002454:Cell Differentiation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D055436:Growth Differentiation Factor 15; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D043484:Proprotein Convertases; D011467:Prostate / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013381:Subtilisins / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D019485:Bone Morphogenetic Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D008565:Membrane Proteins; D011480:Protease Inhibitors; D013196:Dihydrotestosterone; D043484:Proprotein Convertases; D013381:Subtilisins; D017430:Prostate-Specific Antigen