Thrombin receptor expression is upregulated in prostate cancer

Prostate. 2006 Feb 15;66(3):273-82. doi: 10.1002/pros.20326.


Background: Aberrant expression of protease-activated receptors (PARs) has been associated with increased angiogenesis, tumor growth, and metastasis of various cancers. We assessed the status of PAR1 expression in prostate cancer.

Methods: The study compared the abundance levels of PAR1 RNA and protein using real-time reverse-transcriptase polymerase chain reaction and immunoblotting in freshly resected prostate tissues from early localized-stage disease (n=9) to those from patients with advanced metastatic disease (n=7). PAR1 expression and localization was evaluated using immunohistochemical staining of prostate specimens with benign prostatic hyperplasia (n=27), early- (n=32) and advanced-stage (n=22) prostate cancer. Association analyses of PAR1 expression with expression of VEGF-family of growth factors, their receptors, and clinicopathological characteristics of the patients were also performed.

Results: PAR1 RNA expression in advanced-stage prostate was 2.39-fold higher (P=0.024) and its protein expression was 2.75-fold higher (P=5.89x10(-5)) when compared with early-stage prostate cancer. PAR1 expression was localized to endothelial cells in vascular network of prostate tumor areas. The expression of PAR1 correlated statistically significantly with advanced disease stage (P=0.0006) and pre-operative PSA levels (P=0.005) in these samples.

Conclusions: These findings demonstrate that PAR1 expression is increased in prostate cancer. Its predominant expression in vascular network suggests that it may play a direct and crucial role in angiogenesis and could be a relevant target for therapeutic interventions to control or to prevent disease progression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, PAR-1 / biosynthesis*
  • Receptor, PAR-1 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Up-Regulation


  • RNA, Messenger
  • Receptor, PAR-1