Growth of transgenic RAF-induced lung adenomas is increased in mice with a disrupted PPARbeta/delta gene.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors with essential functions in regulating lipid metabolism. Both the PPARbeta (also referred to as PPARdelta) and PPARgamma 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 PPARbeta and PPARgamma in lung tumorigenesis in a transgenic mouse model of RAF-induced lung adenoma using two different strategies: i) crossing with PPARbeta null mice, and ii) chronic treatment with the PPARgamma 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 PPARgamma activation does not affect lung adenoma growth. These results are relevant with respect to the clinical application of drugs modulating the activity of PPARbeta or PPARgamma.
Müller-Brüsselbach
Sabine
S
Institute of Molecular Biology and Tumor Research (IMT), Philipps University, Marburg, Germany.
Ebrahimsade
Schokufe
S
Jäkel
Jörg
J
Eckhardt
Jenny
J
Rapp
Ulf R
UR
Peters
Jeffrey M
JM
Moll
Roland
R
Müller
Rolf
R
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D047494:PPAR delta / Q000235:genetics* / Q000502:physiology; D048068:PPAR-beta / Q000235:genetics* / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics* / Q000502:physiology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D019076:Transgenes
D007004:Hypoglycemic Agents; D047494:PPAR delta; D048068:PPAR-beta; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D019908:Proto-Oncogene Proteins c-raf