Ligand activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) 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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2406-2414
Number of pages9
JournalCarcinogenesis
Volume29
Issue number12
DOIs
StatePublished - 2008

All Science Journal Classification (ASJC) codes

  • Cancer Research

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    Bility, M. T., Devlin-Durante, M. K., Blazanin, N., Glick, A. B., Ward, J. M., Kang, B. H., Kennett, M. J., Gonzalez, F. J., & Peters, J. M. (2008). Ligand activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) inhibits chemically induced skin tumorigenesis. Carcinogenesis, 29(12), 2406-2414. https://doi.org/10.1093/carcin/bgn219