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PPAR Research
Volume 2008, Article ID 309469, 16 pages
Review Article

PPAR 𝜸 and MEK Interactions in Cancer

1Department of Medicine II, Klinikum Rechts der Isar, Technical University, 81675 Munich, Germany
2Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel

Received 4 March 2008; Accepted 29 April 2008

Academic Editor: Dipak Panigrahy

Copyright © 2008 Elke Burgermeister and Rony Seger. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Peroxisome proliferator-activated receptor-gamma (PPAR 𝛾 ) exerts multiple functions in determination of cell fate, tissue metabolism, and host immunity. Two synthetic PPAR 𝛾 ligands (rosiglitazone and pioglitazone) were approved for the therapy of type-2 diabetes mellitus and are expected to serve as novel cures for inflammatory diseases and cancer. However, PPAR 𝛾 and its ligands exhibit a janus-face behaviour as tumor modulators in various systems, resulting in either tumor suppression or tumor promotion. This may be in part due to signaling crosstalk to the mitogen-activated protein kinase (MAPK) cascades. The genomic activity of PPAR 𝛾 is modulated, in addition to ligand binding, by phosphorylation of a serine residue by MAPKs, such as extracellular signal-regulated protein kinases-1/2 (ERK-1/2), or by nucleocytoplasmic compartmentalization through the ERK activators MAPK kinases-1/2 (MEK-1/2). PPAR 𝛾 ligands themselves activate the ERK cascade through nongenomic and often PPAR 𝛾 -independent signaling. In the current review, we discuss the molecular mechanisms and physiological implications of the crosstalk of PPAR 𝛾 with MEK-ERK signaling and its potential as a novel drug target for cancer therapy in patients.