Peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR) signaling pathways in melanoma cells: promising new therapeutic targets?
Peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for a multitude of cellular functions including cell proliferation, cell differentiation, immune responses and apoptosis. Ligands and other agents influencing the PPAR and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in a variety of human cancers. Use of these compounds may represent a potential novel strategy to prevent melanoma pathogenesis and to inhibit melanoma progression. We recently showed that 1,25-dihydroxyvitamin D3 and some of the investigated PPAR ligands inhibited proliferation of the human melanoma cell line MeWo. In addition to this, our results gave an indication of an interconnection of the PPAR and VDR signaling pathways at the level of cross-regulation of their respective transcription factor mRNA levels. The provided link between VDR and PPAR may play an important role in treatment and prevention of melanoma. This review summarizes the currently available data on the roles of the PPARs and the VDR in pathogenesis and progression of melanoma as well as their role as promising future therapeutic targets.
Sertznig
Pit
P
Department of Dermatology, University Hospital Aachen, Pauwelsstr. 30, 52074 Aachen, Germany. psertznig@ukaachen.de
Seifert
Markus
M
Tilgen
Wolfgang
W
Reichrath
Jörg
J
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008545:Melanoma / Q000378:metabolism* / Q000628:therapy; D051379:Mice; D008954:Models, Biological; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000628:therapy
D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D018167:Receptors, Calcitriol