2024-03-28T13:08:52Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/50492021-06-14T11:25:09Zcom_10261_79com_10261_1col_10261_332
DIGITAL.CSIC
author
Grau, Raquel
author
Punzón, Carmen
author
Fresno, Manuel
author
Íñiguez, Miguel Ángel
funder
Ministerio de Educación y Ciencia (España)
funder
European Commission
funder
Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (España)
funder
Instituto de Salud Carlos III
funder
Esteve
funder
Comunidad de Madrid
funder
Fundación Ramón Areces
funder
European Commission
2008-06-12T14:48:12Z
2008-06-12T14:48:12Z
2005-12-13
Biochem. J. (2006) 395 (81–88)
0264-6021
http://hdl.handle.net/10261/5049
1470-8728
http://dx.doi.org/10.13039/501100004587http://dx.doi.org/10.13039/100012818http://dx.doi.org/10.13039/100008054http://dx.doi.org/10.13039/501100000780
Recent evidence indicates that PPAR (peroxisome-proliferator-activated receptor) a ligands possess anti-inflammatory and antitumoural properties owing to their inhibitory effects on the expression of genes that are involved in the inflammatory response. However, the precise molecular mechanisms underlying these effects are poorly understood. In the present study, we show that tumour promoter PMA-mediated induction of genes that are significantly associated with inflammation, tumour growth and metastasis, such as COX-2 (cyclo-oxygenase 2) and VEGF (vascular endothelial growth factor), is inhibited by PPARa ligands in the human colorectal carcinoma cell line SW620. PPARa activators LY-171883 and WY-14,643 were able to diminish transcriptional induction of COX-2 and VEGF by inhibiting AP-1 (activator protein-1)-mediated transcriptional activation induced by PMA or by c-Jun overexpression. The actions of these ligands on AP-1 activation and COX-2 and VEGF transcriptional induction were found to be dependent on PPARa expression. Our studies demonstrate the existence of a negative cross-talk between the PPARa- and AP-1-dependent signalling pathways in these cells. PPARa interfered with at least two steps within the pathway leading to AP-1 activation. First, PPARa activation impaired AP-1 binding to a consensus DNA sequence. Secondly, PPARa ligands inhibited c-Jun transactivating activity. Taken together, these findings provide new insight into the anti-inflammatory and anti-tumoural properties of PPARa activation, through the inhibition of the induction of AP-1-dependent genes that are involved in inflammation and tumour progression
eng
openAccess
Peroxisome-proliferator-activated receptor a (PPARa)
Cyclo-oxygenase 2 (COX-2)
LY-171883
SW620 cell
Vascular endothelial growth factor (VEGF)
WY-14,643
Peroxisome-proliferator-activated receptor a agonists inhibit cyclo-oxygenase 2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1
artículo
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
URL
https://digital.csic.es/bitstream/10261/5049/1/MAI%c3%b1iguez_BiochemJ_81.pdf
File
MD5
aa9a4b6f38ecda1ab95572c2b506f50a
381845
application/pdf
MAIñiguez_BiochemJ_81.pdf
URL
https://digital.csic.es/bitstream/10261/5049/4/MAI%c3%b1iguez_BiochemJ_81.pdf.txt
File
MD5
264d6138b41a479d343d3c476a140d33
52974
text/plain
MAIñiguez_BiochemJ_81.pdf.txt