Differential expression of inducible nitric oxide synthase and peroxisome proliferator-activated receptor gamma in non-small cell lung carcinoma

Abstract 

Both inducible nitric oxide synthase (iNOS) and peroxisome proliferator-activated receptor gamma (PPARγ) are closely associated with the development of human cancer. Although the expression of iNOS has been studied in non-small cell lung carcinoma (NSCLC), the level of PPARγ has not been examined in tumorous and non-tumorous tissues from NSCLC. The present study analysed the levels of both iNOS and PPARγ in NSCLC tissues and in lung cell lines. The possible role of these two molecules in the carcinogenesis of lung cancer was investigated. The expression of iNOS was significantly higher in the tumorous tissues than in the non-tumorous ones. In contrast to this pattern of iNOS protein expression, the level of PPARγ was much lower in the tumorous tissues than in the non-tumorous samples. A similar result was also obtained in vitro using human lung cancer cell lines and normal lung cells. Immunohistochemical examination revealed that PPARγ expression in the non-tumorous tissues was more likely to be located in the nucleus whereas it was present in both the nucleus and cytoplasm of the tumorous tissues. The intensity of iNOS expression was stronger in the nucleus than in the cytoplasm of the tumorous tissues. More than 50% of the cases tested did not express iNOS protein in the non-tumorous tissues. Statistical analysis indicated a negative correlation between iNOS and PPARγ levels in the NSCLC tissues. In conclusion, this study demonstrated differing expressions for iNOS and PPARγ in NSCLC tissues. Since activated PPARγ is able to inhibit the expression of iNOS and the generation of iNOS is particularly associated with the inflammatory and environmental factors of lung cancer risk, this discrepant expression pattern may be associated with the pathogenesis of NSCLC.

Keywords:  Lung cancer, Inducible nitric oxide synthase, Peroxisome proliferator-activated receptor gamma