Ligand activation of peroxisome proliferator-activated receptor {beta}/{delta} (PPAR{beta}/{delta}) inhibits chemically induced skin tumorigenesis

Moses T. Bility; Meghann K. Devlin-Durante; Nicholas Blazanin; Adam B. Glick; Jerrold M. Ward; Boo Hyon Kang; Mary J. Kennett; Frank J. Gonzalez; Jeffrey M. Peters
December 2008
Carcinogenesis;Dec2008, Vol. 29 Issue 12, p2406
Academic Journal
Peroxisome proliferator-activated receptor (PPAR)β/δ-null mice exhibit enhanced tumorigenesis in a two-stage chemical carcinogenesis model as compared with wild-type mice. Previous work showed that ligand activation of PPARβ/δ induces terminal differentiation and inhibits proliferation of primary keratinocytes, and this effect does not occur in the absence of PPARβ/δ expression. In the present studies, the effect of ligand activation of PPARβ/δ on skin tumorigenesis was examined using both in vivo and ex vivo skin carcinogenesis models. Inhibition of chemically induced skin tumorigenesis was observed in wild-type mice administered GW0742, and this effect was likely the result of ligand-induced terminal differentiation and inhibition of replicative DNA synthesis. These effects were not found in similarly treated PPARβ/δ-null mice. Ligand activation of PPARβ/δ also inhibited cell proliferation and induced terminal differentiation in initiated/neoplastic keratinocyte cell lines representing different stages of skin carcinogenesis. These studies suggest that topical administration of PPARβ/δ ligands may be useful as both a chemopreventive and/or a chemotherapeutic approach to inhibit skin cancer.


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