%0 Journal Article
%T Transcriptional and Non-Transcriptional Functions of PPAR¦Â/¦Ä in Non-Small Cell Lung Cancer
%A Davide Genini
%A Ramon Garcia-Escudero
%A Giuseppina M. Carbone
%A Carlo V. Catapano
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0046009
%X Peroxisome proliferator-activated receptor ¦Â/¦Ä (PPAR¦Â/¦Ä) is a nuclear receptor involved in regulation of lipid and glucose metabolism, wound healing and inflammation. PPAR¦Â/¦Ä has been associated also with cancer. Here we investigated the expression of PPAR¦Â/¦Ä and components of the prostaglandin biosynthetic pathway in non-small cell lung cancer (NSCLC). We found increased expression of PPAR¦Â/¦Ä, Cox-2, cPLA2, PGES and VEGF in human NSCLC compared to normal lung. In NSCLC cell lines PPAR¦Â/¦Ä activation increased proliferation and survival, while PPAR¦Â/¦Ä knock-down reduced viability and increased apoptosis. PPAR¦Â/¦Ä agonists induced Cox-2 and VEGF transcription, suggesting the existence of feed-forward loops promoting cell survival, inflammation and angiogenesis. These effects were seen only in high PPAR¦Â/¦Ä expressing cells, while low expressing cells were less or not affected. The effects were also abolished by PPAR¦Â/¦Ä knock-down or incubation with a PPAR¦Â/¦Ä antagonist. Induction of VEGF was due to both binding of PPAR¦Â/¦Ä to the VEGF promoter and PI3K activation through a non-genomic mechanism. We found that PPAR¦Â/¦Ä interacted with the PI3K regulatory subunit p85¦Á leading to PI3K activation and Akt phosphorylation. Collectively, these data indicate that PPAR¦Â/¦Ä might be a central element in lung carcinogenesis controlling multiple pathways and representing a potential target for NSCLC treatment.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046009