Regulation of COX-2 expression in canine prostate carcinoma: increased COX-2 expression is not related to inflammation.
BACKGROUND
Cyclooxygenase-2 (COX-2) expression has been documented in human and canine prostate carcinoma (PCA). Canine PCA is a histologically heterogeneous tumor, sometimes including inflammatory infiltrates. However, it is unknown whether COX-2 expression in canine PCA is related to the histologic type of tumor, to the presence of inflammation, or to both. Moreover, little is known about the mechanisms regulating COX-2 expression in neoplastic tissue.


OBJECTIVE
COX-2 expression is related to the presence of inflammation in canine PCA and correlates with the degree of tumor differentiation.


METHODS
The expression of COX-2 was examined in 28 cases of canine PCA by immunohistochemistry. In addition, a neoplastic and a nonneoplastic canine prostatic cell line were used to investigate the effects of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), phorbol 12-myristate 13-acetate (PMA), epithelial growth factor (EGF), and specific signal transduction pathway inhibitors on COX-2 expression.


RESULTS
Twenty-four of the 28 prostate tumors showed COX-2 expression. The presence of inflammatory infiltrates in tumor tissue was associated with lower COX-2 expression scores. In vitro, TNF-alpha, IL-6, and EGF increased COX-2 expression in nonneoplastic cells but not in PCA cells, where baseline expression was high. COX-2 expression in PCA cells could be suppressed by means of specific phosphatidyl inositol-3 kinase (PI3K), protein kinase C (PKC), or inhibitor of extracellular signal-related kinase (ERK/MAPK) inhibitors.


CONCLUSIONS
COX-2 is expressed in canine PCA; however, expression is not related to the presence of inflammatory infiltrates. This conclusion is further supported by the finding that the cytokines TNF-alpha and IL-6 and their involved signaling pathways do not stimulate COX-2 expression in malignant canine prostate cells.
L'Eplattenier
Henry F
HF
Department of Clinical Sciences of Companion Animals, University of Utrecht, Utrecht, The Netherlands. leplatth@zonnet.nl
Lai
Chen Li
CL
van den Ham
René
R
Mol
Jan
J
van Sluijs
Frederick
F
Teske
Erik
E
D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004283:Dog Diseases / Q000201:enzymology*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D007249:Inflammation / Q000201:enzymology*; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C