Establishing the Role of PPARβ/δ in Carcinogenesis.
The role of the nuclear hormone receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) in carcinogenesis is controversial because conflicting studies indicate that it both inhibits and promotes tumorigenesis. In this review, we focus on recent studies on PPARβ/δ including the significance of increased or decreased PPARβ/δ expression in cancers; a range of opposing mechanisms describing how PPARβ/δ agonists, antagonists, and inverse agonists regulate tumorigenesis and/or whether there may be cell context-specific mechanisms; and whether activating or inhibiting PPARβ/δ is feasible for cancer chemoprevention and/or therapy. Research questions that need to be addressed are highlighted to establish whether PPARβ/δ can be effectively targeted for cancer chemoprevention.
Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: jmp21@psu.edu.
Jeffrey M
JM
Peters
Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA.
Frank J
FJ
Gonzalez
Institute of Molecular Biology and Tumor Research, Center for Tumor Biology and Immunology, Philipps University, Hans-Meerwein-Straße 3, 35043 Marburg, Germany.
Rolf
R
Müller
D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D047494:PPAR delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048068:PPAR-beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
D047494:PPAR delta; D048068:PPAR-beta
cancer; chemoprevention; mechanisms; peroxisome proliferator-activated receptor-β/δ; transcription factor