Regulation of COX‐2 Expression in Canine Prostate Carcinoma: Increased COX‐2 Expression is Not Related to Inflammation

Abstract

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. Hypothesis: 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‐ç (TNF‐ç), 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‐ç, 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 and Clinical Importance: 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‐ç and IL‐6 and their involved signaling pathways do not stimulate COX‐2 expression in malignant canine prostate cells.