| First Author | Li MY | Year | 2010 |
| Journal | Am J Respir Cell Mol Biol | Volume | 43 |
| Issue | 6 | Pages | 674-83 |
| PubMed ID | 20081051 | Mgi Jnum | J:179957 |
| Mgi Id | MGI:5304655 | Doi | 10.1165/rcmb.2009-0349OC |
| Citation | Li MY, et al. (2010) Roles of peroxisome proliferator-activated receptor-alpha and -gamma in the development of non-small cell lung cancer. Am J Respir Cell Mol Biol 43(6):674-83 |
| abstractText | Peroxisome proliferator-activated receptor (PPAR)-alpha and PPARgamma participate in cell proliferation and apoptosis. Few studies have simultaneously investigated both PPARalpha and PPARgamma in lung cancers in vivo. The roles of PPARalpha and -gamma were investigated in the development of pulmonary tumors induced in the adult A/J mouse by treatment with 4-(methylnitrosamino)-l-(3-pyridyl)-lbutanone (NNK). Compared with the normal lung tissues, PPARgamma expression was much higher in the NNK-induced lung tumor tissues. However, PPARgamma transcriptional activity, and the levels of two major endogenous PPARgamma ligands, 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, were significantly lower in the NNK-treated lung tissues. The ligand changes in mice were confirmed in human lung cancer tissues. Along with the alteration of PPARgamma and its endogenous ligands, the level of PPARalpha and its activity were increased in the NNK-induced mouse lung tumors. Treatment of mice with the synthetic PPARgamma ligand, pioglitazone, significantly inhibited the formation of mouse lung tumors induced by NNK. Our study demonstrated that the reduction of endogenous PPARgamma ligands and increased PPARalpha occurred before the formation of lung tumors, indicating that the molecular changes play a role in lung carcinogenesis. The results suggest that the enhancement of PPARgamma activity with its ligands, and the suppression of PPARalpha with its inhibitors, may prevent the formation of lung tumors, as well as accelerate the therapy of lung cancer. Our findings may also reveal the possibility of using the level of endogenous PPARgamma ligands and the activities of PPARgamma or PPARalpha as tumor markers for lung cancer. |
