Details

Autor(en) / Beteiligte

• Bility, Moses T.
• Devlin-Durante, Meghann K.
• Blazanin, Nicholas
• Glick, Adam B.
• Ward, Jerrold M.
• Kang, Boo Hyon
• Kennett, Mary J.
• Gonzalez, Frank J.
• Peters, Jeffrey M.

Titel

Ligand activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) inhibits chemically induced skin tumorigenesis

Ist Teil von

• Carcinogenesis (New York), 2008-12, Vol.29 (12), p.2406-2414

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2008

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.