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Ligand activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) inhibits chemically induced skin tumorigenesis
- Source :
- Carcinogenesis. 29:2406-2414
- Publication Year :
- 2008
- Publisher :
- Oxford University Press (OUP), 2008.
-
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.
- Subjects :
- chemistry.chemical_classification
Cancer Research
Cell growth
Cellular differentiation
Peroxisome proliferator-activated receptor
General Medicine
Biology
GW0742
medicine.disease_cause
Cell biology
medicine.anatomical_structure
chemistry
Biochemistry
medicine
Peroxisome proliferator-activated receptor delta
Keratinocyte
Receptor
Carcinogenesis
Subjects
Details
- ISSN :
- 14602180 and 01433334
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi...........fcd52a1688bfeb99fd330a20a023ff79