Cancer Prevention Research Nonsteroidal Anti-inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis in Transgenic Mice

Abstract

The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inhibits gastrointestinal tumorigenesis in NAG-1 transgenic mice (C57/BL6 background). In the present study, we investigated whether the NAG-1 protein would alter urethane-induced pulmonary lesions in NAG-1 transgenic mice on an FVB background (NAG-1). NAG-1 mice had both decreased number and size of urethane-induced tumors, compared with control littermates (NAG-1 = 16 ± 4 per mouse versus control = 20 ± 7 per mouse, P < 0.05). Urethane-induced pulmonary adenomas and adenocarcinomas were observed in control mice; however, only pulmonary adenomas were observed in NAG-1 mice. Urethane-induced tumors from control littermates and NAG-1 mice highly expressed proteins in the arachidonic acid pathway (cyclooxygenases 1/2, prostaglandin E synthase, and prostaglandin E2 receptor) and highly activated several kinases (phospho-Raf-1 and phosphorylated extracellular signal-regulated kinase 1/2). However, only urethane-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation was decreased in NAG-1 mice. Furthermore, significantly increased apoptosis in tumors of NAG-1 mice compared with control mice was observed as assessed by caspase-3/7 activity. In addition, fewer inflammatory cells were observed in the lung tissue isolated from urethane-treated NAG-1 mice compared with control mice. These results paralleled in vitro assays using humanA549 pulmonary carcinoma cells. Less phosphorylated p38MAPKwas observed in cells overexpressing NAG-1 compared with control cells. Overall, our study revealed for the first time that the NAG-1 protein inhibits urethane-induced tumor formation, probably mediated by the p38 MAPK pathway, and is a possible new target for lung cancer

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@inproceedings{Cekanova2009CancerPR, title={Cancer Prevention Research Nonsteroidal Anti-inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis in Transgenic Mice}, author={Maria Cekanova and Seong-Ho Lee and Robert L. Donnell and Mugdha Sukhthankar and Thomas E. Eling and Susan M . Fischer and Seung Joon Baek}, year={2009} }