Original Article

Overexpression of protease-activated receptors-1,-2, and-4 (PAR-1, -2, and -4) in prostate cancer†

  1. Peter C. Black1,
  2. Gregory J. Mize1,2,
  3. Peter Karlin1,2,
  4. Daniel L. Greenberg2,3,
  5. Sarah J. Hawley5,
  6. Lawrence D. True4,
  7. Robert L. Vessella1,
  8. Thomas K. Takayama1,2,*

Article first published online: 20 MAR 2007

DOI: 10.1002/pros.20503

Issue

The Prostate

The Prostate

Volume 67, Issue 7, pages 743–756, 15 May 2007

Additional Information

How to Cite

Black, P. C., Mize, G. J., Karlin, P., Greenberg, D. L., Hawley, S. J., True, L. D., Vessella, R. L. and Takayama, T. K. (2007), Overexpression of protease-activated receptors-1,-2, and-4 (PAR-1, -2, and -4) in prostate cancer. Prostate, 67: 743–756. doi: 10.1002/pros.20503

Author Information

  1. 1

    Department of Urology, University of Washington, Seattle, Washington

  2. 2

    Department of Biochemistry, University of Washington, Seattle, Washington

  3. 3

    Department of Medicine, University of Washington, Seattle, Washington

  4. 4

    Department of Pathology, University of Washington, Seattle, Washington

  5. 5

    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington

*Box 357350, 1959 NE Pacific St., Seattle, WA 98195-7350.

  1. †

    Peter C. Black and Gregory J. Mize contributed equally to the study.

Publication History

  1. Issue published online: 28 MAR 2007
  2. Article first published online: 20 MAR 2007
  3. Manuscript Accepted: 12 JUL 2006
  4. Manuscript Received: 16 MAY 2006

Funded by

  • Department of Defense. Grant Number: DAMD17-03-01-0039
  • National Institutes of Health. Grant Number: HL16919
  • SMT Foundation

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Keywords:

  • PAR-1;
  • PAR-2;
  • PAR-4;
  • LNCaP;
  • prostate cancer

Abstract

BACKGROUND

Although protease-activated receptors (PARs) have been described to play a role in different malignancies, their expression and biological activity in prostate cancer are mostly unknown.

METHODS

PAR expression in radical prostatectomy specimens was investigated by immunohistochemistry (IHC, 40 patients) and RT-PCR. Their role in LNCaP prostate cancer cell migration and Rac1/Cdc42 signaling was assessed with Boyden chamber analysis and Western blot, respectively.

RESULTS

PAR mRNA expression was higher in cancer, and protein expression was increased in PAR-1 (45%), PAR-2 (42%), and PAR-4 (68%), compared to normal glands. Increased PAR-1 (periglandular stroma) was associated with higher rates of biochemical recurrence (median follow-up, 5 years; P = 0.006). LNCaP migration was enhanced twofold and Rac1/Cdc42 signaling was activated by stimulation of PAR-1 and PAR-2.

CONCLUSIONS

PARs are overexpressed in prostate cancer and may serve as potential predictors of recurrence. The data suggest potential role of PARs in autocrine and paracrine mechanisms of prostate cancer. Prostate 67: 743–756, 2007. © 2007 Wiley-Liss, Inc.

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