Activation of the thromboxane A2 pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage.
OBJECTIVE
We investigated the potential involvement of the thromboxane A(2) (TXA(2)) pathway in human prostate cancer (PCa).


METHODS
Expression of cyclooxygenase-2 (COX-2), TXA(2) synthase (TXS), and TXA(2) receptors (TPRs), the main actors of the TXA(2) pathway, was analyzed on serial tissue sections from 46 human PCa specimens.


RESULTS
The expression levels of COX-2, TXS, and TPRs were significantly higher in malignant than in corresponding nontumoral prostatic epithelial cells. Increased immunoreactivity for these antigens was also observed in high-grade prostate intraepithelial neoplasia (HGPIN) glands. COX-2, TXS, and TPR proteins usually displayed a coordinated overexpression pattern in PCa lesions, as assessed in serial tissue sections. Increased levels of these proteins in the tumors were all significantly associated with higher Gleason scores and pathologic stages.


CONCLUSIONS
Proteins specifically involved in the TXA(2) pathway are up-regulated in human PCa and their level of expression is associated with tumor extraprostatic extension and loss of differentiation. Our study is the first to examine simultaneously all key proteins involved in this pathway including TXA(2) receptors and results suggest that the TXA(2) pathway may be a potential target for PCa prevention/therapy.
Dassesse
Thibaut
T
Metastasis Research Laboratory, Center of Experimental Cancer Research, University of Liège, B-4000 Liège, Belgium.
de Leval
Xavier
X
de Leval
Laurence
L
Pirotte
Bernard
B
Castronovo
Vincent
V
Waltregny
David
D
D000368:Aged; D002454:Cell Differentiation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000473:pathology*; D021381:Protein Transport; D017482:Receptors, Thromboxane / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000378:metabolism
D008565:Membrane Proteins; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013930:Thromboxane-A Synthase