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Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1)

Yamaguchi, K., Whitlock, N.C., Liggett, J.L., Legendre, A.M., Fry, M.M., Baek, S.J.
Veterinary journal 2008 v.175 no.1 pp. 89-95
dogs, dog diseases, disease prevention, drug therapy, antineoplastic agents, nonsteroidal anti-inflammatory agents, drug evaluation, anticarcinogenic activity, in vitro studies, cell lines, osteosarcoma, molecular genetics, genes, transforming growth factor beta, gene expression regulation, gene induction, inhibitors, carcinogenesis, phylogeny
Nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1), a divergent member of the transforming growth factor β superfamily, was previously identified as a gene induced by several anti-tumorigenic compounds, including NSAIDs and peroxisome proliferator-activated receptor γ (PPARγ) ligands in humans. In this study, canine NAG-1 was characterised from a canine genomic database. Gene induction by some NSAIDs and PPARγ ligands was demonstrated in canine osteosarcoma cell lines. Phylogenetic analysis indicates that canine NAG-1 is more homologous with the corresponding mouse and rat genes than with human NAG-1. Expression of canine NAG-1 was increased by treatment with piroxicam and SC-560 (NSAIDs) and the PPARγ ligand rosiglitazone. This study demonstrates that canine NAG-1 is up-regulated by some anti-tumorigenic compounds in osteosarcoma cell lines and may provide an important target of chemotherapy in canine cancer.