Expression of functional protease-activated receptor 1 in human prostate cancer cell lines.
Functional protease-activated receptors (PAR) are expressed by a variety of malignant cells. In the present study, RT-PCR assays demonstrated the expression of the thrombin receptor PAR-1 mRNA in human prostate cancer cell lines DU 145, LnCAP, and SV40-immortalized human prostate epithelial cell line PNT1A. In contrast, the additional thrombin receptors PAR-3 and PAR-4 were not detected. PAR-1 protein localized to the cellular surface was detected by flow cytometry in all three cell lines. To demonstrate the functional importance of the PAR-1, the effects of different concentrations of thrombin on cell proliferation kinetics were assessed. The treatment of growth-arrested cells with varying concentrations of thrombin demonstrated dose- and time-dependent effects. At low concentration (<0.5 U/ml), thrombin induced proliferation of all prostate-derived cell lines. Thrombin at higher concentration (1.0 U/ml) initially stimulated PNT1A and LnCAP cells to proliferate (time of thrombin application 24 h and 48 h) followed by inhibited growth when assessed after 72 h of incubation. In contrast, 1.0 U/ml thrombin caused earlier inhibition of DU 145 proliferation starting at 48 h of incubation. Our results suggest that PAR-1 mediates the proliferation-modulating effects of thrombin on prostate cancer cells.
Liu
Jian
J
University of Rostock, Medical Faculty, Institute of Clinical Chemistry and Pathobiochemistry, Ernst-Heydemann-Strasse 6, 18057 Rostock, Germany.
Bastian
Manuela
M
Kohlschein
Peter
P
Schuff-Werner
Peter
P
Steiner
Michael
M
D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D013917:Thrombin / Q000008:administration & dosage; D013997:Time Factors; D014018:Tissue Distribution
D012333:RNA, Messenger; D044463:Receptor, PAR-1; D013917:Thrombin