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Nonsteroidal Antiinflammatory Drug Activated Gene (NAG‐1) as a Chemopreventive Target in Canine Tumorigenesis
Author(s) -
Whitlock Nichelle Chantil,
Yamaguchi Kiyoshi,
Baek Seung
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a420-a
Subject(s) - carcinogenesis , gene , sulindac , biology , cancer research , piroxicam , gene expression , osteosarcoma , complementary dna , microbiology and biotechnology , nonsteroidal , pharmacology , medicine , pathology , biochemistry , alternative medicine
Nonsteroidal anti‐inflammatory drug (NSAID)‐activated gene (NAG‐1), a divergent member of the transforming growth factor‐β (TGF‐β) superfamily, was previously identified as a gene induced by several anti‐tumorigenic compounds, including NSAIDs and peroxisome proliferator‐activated receptor γ (PPARγ) ligands. NAG‐1 was also found to have anti‐tumorigenic and/or pro‐apoptotic activities in several types of human cancer cells. However, canine NAG‐1 has yet to be characterized. In this report, we show that the properties of NAG‐1 expression exist in canine osteosarcoma. The predicted NAG‐1 cDNA sequence encodes a conserved nine cysteine residues and a RXXR site in the middle of the pro‐peptide. Phylogenetic analysis indicated that canine NAG‐1 was more homologous with mouse and rat than with human. The NAG‐1 protein was detected in canine liver, lung, and kidney tissues. We also found that, as reported previously for human NAG‐1, expression of canine NAG‐1 is increased by treatment with some NSAIDs, including piroxicam and SC‐560. In addition, the PPARγ ligand rosiglitazone also increased NAG‐1 expression, as assessed by reverse transcription‐PCR. This study demonstrates that, like human NAG‐1, canine NAG‐1 is up‐regulated by NSAIDs as well as anti‐tumorigenic compounds in osteosarcoma and may provide an important role of NAG‐1 in prevention of canine cancers.