The effect of PPARγ ligands on UV- or chemically-induced carcinogenesis in mouse skin

Guobin He, Stephanie Muga, Philippe Thuillier, Ronald A. Lubet, Susan M. Fischer

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand activated transcription factor. There have been suggestions that PPARγ ligands may have utility in preventing tumor development in rodent mammary glands and colon. The recent finding that mice lacking one allele of the PPARγ gene were significantly more susceptible to 7,12-dimethylbenz[a] anthracene (DMBA)-induced skin carcinogenesis compared to wild-type mice highlights mouse skin as another potential organ in which PPARγ ligands may be effective as chemopreventive agents. In this study, we assessed the effect of two PPARγ ligands (rosiglitazone and troglitazone) on UV and DMBA/12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse skin carcinogenesis, two of the most commonly used mouse skin carcinogenesis models. Unexpectedly, neither rosiglitazone (dietary 200 ppm) nor troglitazone (topical 100 μg) significantly inhibited UV-induced skin tumor development in SKH-1 hairless mice. Likewise, dietary rosiglitazone did not statistically significantly inhibit DMBA/TPA-induced skin tumor development. Interestingly, dietary troglitazone significantly inhibited basal level keratinocyte proliferation as shown by 5-bromo-2′-deoxyuridine (BrdU) labeling, but it had no effect on TPA-induced epidermal cell proliferation. Northern blot analysis showed that PPARγ expression was extremely low in normal mouse epidermis and was virtually undetectable in skin tumors. Collectively, our data suggest that PPARγ ligands may not be useful In the prevention of chemically or UV-induced skin tumors.

Original languageEnglish (US)
Pages (from-to)198-206
Number of pages9
JournalMolecular Carcinogenesis
Volume43
Issue number4
DOIs
StatePublished - Aug 1 2005

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Keywords

  • Chemoprevention
  • Rosiglitazone
  • Skin carcinogenesis
  • Troglitazone

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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