Gene interactions and pathways from curated databases and text-mining
PloS one 2012, PMID: 23049921

Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer.

Genini, Davide; Garcia-Escudero, Ramon; Carbone, Giuseppina M; Catapano, Carlo V

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a nuclear receptor involved in regulation of lipid and glucose metabolism, wound healing and inflammation. PPARβ/δ has been associated also with cancer. Here we investigated the expression of PPARβ/δ and components of the prostaglandin biosynthetic pathway in non-small cell lung cancer (NSCLC). We found increased expression of PPARβ/δ, Cox-2, cPLA(2), PGES and VEGF in human NSCLC compared to normal lung. In NSCLC cell lines PPARβ/δ activation increased proliferation and survival, while PPARβ/δ knock-down reduced viability and increased apoptosis. PPARβ/δ 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 PPARβ/δ expressing cells, while low expressing cells were less or not affected. The effects were also abolished by PPARβ/δ knock-down or incubation with a PPARβ/δ antagonist. Induction of VEGF was due to both binding of PPARβ/δ to the VEGF promoter and PI3K activation through a non-genomic mechanism. We found that PPARβ/δ interacted with the PI3K regulatory subunit p85α leading to PI3K activation and Akt phosphorylation. Collectively, these data indicate that PPARβ/δ might be a central element in lung carcinogenesis controlling multiple pathways and representing a potential target for NSCLC treatment.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Non-Small-Cell Lung, Inflammation, Lung Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

VEGF → PI3K: " Induction of VEGF was due to both binding of PPARß/d to the VEGF promoter and PI3K activation through a non-genomic mechanism "

Manually curated Databases

No curated data.