Premium
Induction of PPARβ and prostacyclin (PGI 2 ) synthesis by Raf signaling: failure of PGI 2 to activate PPARβ
Author(s) -
Fauti Tanja,
MüllerBrüsselbach Sabine,
Kreutzer Mihaela,
Rieck Markus,
Meissner Wolfgang,
Rapp Ulf,
Schweer Horst,
Kömhoff Martin,
Müller Rolf
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.05055.x
Subject(s) - prostacyclin , peroxisome proliferator activated receptor , nuclear receptor , receptor , chemistry , arachidonic acid , agonist , microbiology and biotechnology , medicine , endocrinology , biology , biochemistry , enzyme , transcription factor , gene
A role for the nuclear receptor peroxisome proliferator‐activated receptor‐β (PPARβ) in oncogenesis has been suggested by a number of observations but its precise role remains elusive. Prostaglandin I 2 (PGI 2 , prostacyclin), a major arachidonic acid (AA) derived cyclooxygenase (Cox) product, has been proposed as a PPARβ agonist. Here, we show that the 4‐hydroxytamoxifen (4‐OHT) mediated activation of a C‐Raf‐estrogen receptor fusion protein leads to the induction of both the PPARβ and Cox‐2 genes, concomitant with a dramatic increase in PGI 2 synthesis. Surprisingly, however, 4‐OHT failed to activate PPARβ transcriptional activity, indicating that PGI 2 is insufficient for PPARβ activation. In agreement with this conclusion, the overexpression of ectopic Cox‐2 and PGI 2 synthase (PGIS) resulted in massive PGI 2 synthesis but did not activate the transcriptional activity of PPARβ. Conversely, inhibition of PGIS blocked PGI 2 synthesis but did not affect the AA mediated activation of PPARβ. Our data obtained with four different cell types and different experimental strategies do not support the prevailing opinion that PGI 2 plays a significant role in the regulation of PPARβ.