Expression of functional protease-activated receptor 1 in human prostate cancer cell lines

Urol Res. 2003 Jul;31(3):163-8. doi: 10.1007/s00240-003-0309-2. Epub 2003 Mar 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Osmolar Concentration
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Receptor, PAR-1 / genetics
  • Receptor, PAR-1 / metabolism*
  • Thrombin / administration & dosage
  • Time Factors
  • Tissue Distribution


  • RNA, Messenger
  • Receptor, PAR-1
  • Thrombin