Premium
Effects of Lung Carcinogens on PPARgamma Activity in A549 Cell Line
Author(s) -
Carrasco Nestor,
Tennis Meredith,
Nield Lori
Publication year - 2015
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.29.1_supplement.576.8
Subject(s) - peroxisome proliferator activated receptor gamma , agonist , chemistry , endogeny , receptor , cancer research , endocrinology , medicine , downregulation and upregulation , transcription factor , peroxisome proliferator activated receptor , biology , biochemistry , gene
PPARgamma (PPARG) is a transcription factor that associates with retinoic acid receptor to enhance transcription of genes regulating pathways of adipogenesis, macrophage programming, growth, and inflammation. PPARg agonists are effective at preventing lung cancer in mice and cause regression of human pre‐neoplastic lung lesions. However, the mechanisms by which PPARg prevents lung cancer progression are not completely understood. Herein, we examined the effects of endogenous and exogenous PPAR agonists on expression of PPARg‐regulated genes (E‐cadherin and Ptgs2) in human lung cancer A549 cells. We treated cells with the endogenous PPARg agonist 15‐PGJ2and exogenous agonists pioglitazone (Pio) and iloprost. We also tested acrolein (component of cigarette smoke) and 4‐hydroxynonenol (4‐HNE; increased in the lungs of smokers). These molecules are chemically related to 15‐Deoxy‐Δ12,14‐prostaglandin J2 (15‐PGJ2), and 4‐HNE has been shown to enhance PPARg activity. We found that Pio, iloprost, and 15‐PGJ2increased expression of E‐cadherin at 24h and 48h of exposure. HPGD expression was increased at 24 h with Pio, iloprost, 15‐Deoxy‐Δ12,14‐prostaglandin J2, and 4‐HNE, but returned to baseline by 48 h. NFκB protein is down‐regulated in the presence of PPARg, but its gene expression increased with Pio, iloprost, 15‐Deoxy‐Δ12,14‐prostaglandin J2, and acrolein exposure at 24 h, indicating that decreased protein leads to increased transcription. The peak of agonist‐induced expression effects occurs by 24 h. Increases in expression of the Pio off‐target regulated gene HPGD with agonists other than Pio indicates that regulation of these genes is more complicated than was previously thought.