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Thrombin receptor expression is upregulated in prostate cancer.

AbstractBACKGROUND:
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.
AuthorsVarsha Kaushal, Manish Kohli, Richard A Dennis, Eric R Siegel, Walter W Chiles, Perkins Mukunyadzi
JournalThe Prostate (Prostate) Vol. 66 Issue 3 Pg. 273-82 (Feb 15 2006) ISSN: 0270-4137 [Print] United States
PMID16245281 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright (c) 2005 Wiley-Liss, Inc.
Chemical References
  • RNA, Messenger
  • Receptor, PAR-1
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic (genetics, pathology)
  • Prostatic Hyperplasia (genetics, metabolism, pathology)
  • Prostatic Neoplasms (blood supply, genetics, metabolism, pathology)
  • RNA, Messenger (biosynthesis, genetics)
  • Receptor, PAR-1 (biosynthesis, genetics)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Up-Regulation

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