Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer.
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 bios...
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2012
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oai:doaj.org-article:9ac73be4b28044339e5ff6ec2ac3344f2021-11-18T08:14:06ZTranscriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer.1932-620310.1371/journal.pone.0046009https://doaj.org/article/9ac73be4b28044339e5ff6ec2ac3344f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049921/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Peroxisome 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.Davide GeniniRamon Garcia-EscuderoGiuseppina M CarboneCarlo V CatapanoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e46009 (2012) |
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Medicine R Science Q Davide Genini Ramon Garcia-Escudero Giuseppina M Carbone Carlo V Catapano Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer. |
description |
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. |
format |
article |
author |
Davide Genini Ramon Garcia-Escudero Giuseppina M Carbone Carlo V Catapano |
author_facet |
Davide Genini Ramon Garcia-Escudero Giuseppina M Carbone Carlo V Catapano |
author_sort |
Davide Genini |
title |
Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer. |
title_short |
Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer. |
title_full |
Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer. |
title_fullStr |
Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer. |
title_full_unstemmed |
Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer. |
title_sort |
transcriptional and non-transcriptional functions of pparβ/δ in non-small cell lung cancer. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/9ac73be4b28044339e5ff6ec2ac3344f |
work_keys_str_mv |
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_version_ |
1718422059808194560 |