Growth of transgenic RAF-induced lung adenomas is increased in mice with a disrupted PPARbeta/delta gene
Müller-Brüsselbach, S.; Ebrahimsade, S.; Jäkel, Jörg.; Eckhardt, J.; Rapp, U.R.; Peters, J.M.; Moll, R.; Müller, R.
International Journal of Oncology 31(3): 607-611
2007
ISSN/ISBN: 1019-6439 PMID: 17671688 Document Number: 614019
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors with essential functions in regulating lipid metabolism. Both the PPARSS (also referred to as PPAR delta) and PPAR gamma subtype have been reported to either attenuate or potentiate tumorigenesis in a number of different models of intestinal and skin carcinogenesis. In the present study, we have addressed the role of PPARSS and PPAR gamma in lung tumorigenesis in a transgenic mouse model of RAF-induced lung adenoma using two different strategies: i) crossing with PPARSS null mice, and ii) chronic treatment with the PPAR gamma agonist rosiglitazone. Histological examination revealed a significant enhancement of tumor growth in mice lacking one or both alleles of Pparb, but no significant effect in response to rosiglitazone. These observations indicate i) that RAF-induced lung tumorigenesis is attenuated in mice with a disrupted Pparb gene, and ii) that chronic PPAR gamma activation does not affect lung adenoma growth. These results are relevant with respect to the clinical application of drugs modulating the activity of PPARSS or PPAR gamma.