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 Bleier Glick, Jerrold M. Ward, Boo Hyon Kang, Mary J. Kennett, Frank J. Gonzalez, Jeffrey Maurice Peters

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 - Dec 15 2008

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Peroxisome Proliferator-Activated Receptors
Carcinogenesis
Ligands
Skin
Keratinocytes
Chemical Models
Topical Administration
Skin Neoplasms
Cell Proliferation
Cell Line
DNA

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Bility, Moses T. ; Devlin-Durante, Meghann K. ; Blazanin, Nicholas ; Glick, Adam Bleier ; Ward, Jerrold M. ; Kang, Boo Hyon ; Kennett, Mary J. ; Gonzalez, Frank J. ; Peters, Jeffrey Maurice. / Ligand activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) inhibits chemically induced skin tumorigenesis. In: Carcinogenesis. 2008 ; Vol. 29, No. 12. pp. 2406-2414.
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Ligand activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) inhibits chemically induced skin tumorigenesis. / Bility, Moses T.; Devlin-Durante, Meghann K.; Blazanin, Nicholas; Glick, Adam Bleier; Ward, Jerrold M.; Kang, Boo Hyon; Kennett, Mary J.; Gonzalez, Frank J.; Peters, Jeffrey Maurice.

In: Carcinogenesis, Vol. 29, No. 12, 15.12.2008, p. 2406-2414.

Research output: Contribution to journalArticle

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AU - Glick, Adam Bleier

AU - Ward, Jerrold M.

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AU - Gonzalez, Frank J.

AU - Peters, Jeffrey Maurice

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