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Vet Pathol 43:656-666 (2006)
© 2006 American College of Veterinary Pathologists

Cyclooxygenase-2 Expression in Normal and Neoplastic Canine Mammary Cell Lines

M. Brunelle, E. A. Sartin, L. G. Wolfe, J. Sirois and M. Doré

Département de pathologie et microbiologie (MB, MD), Centre de recherche en reproduction animale (JS), Faculté de médecine vétérinaire, Université de Montréal, St-Hyacinthe, Québec, Canada; and Department of Pathobiology (EAS, LGW), College of Veterinary Medicine, Auburn University, AL

Mammary cancer is the most common cancer in female dogs. Induction of cyclooxygenase-2 (COX-2), a key enzyme in prostaglandins (PGs) biosynthesis, has been demonstrated in various cancers in humans and dogs, including mammary cancer. The objective of this study was to investigate the expression and regulation of COX-2 in canine mammary epithelial cells. Cell lines derived from normal and neoplastic canine mammary glands were cultured in the absence or presence of phorbol 12-myristate 13-acetate (PMA), and immunoblots, immunocytochemistry, radioimmunoassays, and a cell proliferation assay were used to study COX-2 expression and PGs production. Results showed that the neoplastic cell line CMT12 constitutively overexpressed COX-2 protein whereas other mammary cell lines expressed low to undetectable basal levels of COX-2 protein. Basal PGE2 production was significantly higher (P < .05) in CMT12 compared to other cell lines. Levels of COX-2 protein in CMT12 decreased in a time-dependent manner with serum starvation, and PMA stimulation induced a strong time-dependent increase in COX-2 protein. Treatment of CMT12 cells with NS-398 (a specific COX-2 inhibitor) significantly blocked PGE2 synthesis and reduced cell proliferation (P < .05). These results indicate that some neoplastic canine mammary cell lines constitutively overexpress COX-2, and that COX-2 inhibition decreases PGE2 production and cell proliferation, supporting a role for COX-2 and PGs in canine mammary oncogenesis.

Key words: Cancer; cyclooxygenase; dogs; mammary tumors; prostaglandins.

Request reprints from Dr. M Doré, Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal, C.P. 5000, St-Hyacinthe, Québec J2S 7C6 (Canada). E-mail: monique.dore{at}umontreal.ca






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