Original Article
Expression and regulation of cyclooxygenase-2 in normal and neoplastic canine keratinocytes
N. Pronovost1, M. M. Suter2, E. Mueller2, J. Sirois3 and M. Doré1*
Squamous cell carcinoma (SCC) is one of the most common cancers in dogs, yet relatively little is known about the molecular events involved in its development.
Increasing evidence implicates cyclooxygenase-2 (COX-2) in the pathogenesis of various cancers in humans and animals. COX-2 overexpression has recently been demonstrated in canine SCCs.
The objective of our study was to characterize the expression and regulation of COX-2 in normal and neoplastic canine keratinocytes (CKs) to provide an in vitro system to investigate the implication of COX-2 in SCC oncogenesis in dogs.
Cell lines derived from normal CKs and neoplastic CKs (SCCs) were cultured in the absence or presence of agonists, and immunoblots, immunocytochemistry, radioimmunoassays and a cell proliferation assay were used to characterize COX-2 expression and action.
Results showed that neoplastic keratinocytes had a higher basal COX-2 expression than normal keratinocytes.
In both cell lines, stimulation with the tumour promoter phorbol 12-myristate 13-acetate induced a time-dependent increase in COX-2 protein, with COX-2 induction being stronger in cancerous SCC than in normal CK cells.
Moreover, SCC cells produced significantly more PGE2 than CK cells, under both baseline and stimulated conditions (P < 0.05). NS-398, a selective COX-2 inhibitor, inhibited prostaglandin (PG)E2 synthesis and decreased proliferation of CK and SCC cells (P < 0.05).
Collectively, our results indicate that the canine neoplastic keratinocyte SCC cell line expresses more COX-2 and produces more PGE2 than the normal keratinocyte CK cell line, thus providing an in vitro system to study the molecular basis of elevated COX-2 expression in SCCs in dogs.
Source: Pronovost, N., Suter, M. M., Mueller, E., Sirois, J. & Doré, M. (2004): Expression and regulation of cyclooxygenase-2 in normal and neoplastic canine keratinocytes. In: Veterinary and Comparative Oncology 2 (4), 222-233.
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