{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:15:22Z","timestamp":1779203722036,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,4,18]],"date-time":"2012-04-18T00:00:00Z","timestamp":1334707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies suggest that peroxisome proliferator\u2010activated receptor gamma (PPAR\u03b3) agonists may have cancer chemopreventive activity. Other studies have shown that loss of epidermal PPAR\u03b3 results in enhanced chemical carcinogenesis in mice <jats:italic>via<\/jats:italic> unknown mechanisms. However, ultraviolet B (UVB) exposure represents the primary etiological agent for skin cancer formation and the role of PPAR\u03b3 in photobiology and photocarcinogenesis is unknown. In previous studies, we demonstrated that UVB irradiation of cells results in the formation of oxidized glycerophosphocholines that exhibit PPAR\u03b3 ligand activity. We therefore hypothesized that PPAR\u03b3 would prove to be a chemopreventive target in photocarcinogenesis. We first showed that UVB irradiation of mouse skin causes generation of PPAR\u03b3 agonist species <jats:italic>in vivo<\/jats:italic>. We then generated SKH\u20101 hairless, albino mice deficient in epidermal <jats:italic>Pparg<\/jats:italic> (<jats:italic>Pparg<\/jats:italic>\u2212\/\u2212<jats:sup>epi<\/jats:sup>) using a cytokeratin 14 driven Cre\u2010LoxP strategy. Using a chronic model of UVB photocarcinogenesis, we next showed that <jats:italic>Pparg<\/jats:italic>\u2212\/\u2212<jats:sup>epi<\/jats:sup> mice exhibit an earlier onset of tumor formation, increased tumor burden and tumor progression. Increased tumor burden in <jats:italic>Pparg<\/jats:italic>\u2212\/\u2212<jats:sup>epi<\/jats:sup> mice was accompanied by a significant increase in epidermal hyperplasia and p53 positive epidermal cells in surrounding skin lacking tumors. After acute UVB irradiation, <jats:italic>Pparg<\/jats:italic>\u2212\/\u2212<jats:sup>epi<\/jats:sup> mice exhibited an augmentation of both UVB\u2010induced Caspase 3\/7 activity and inflammation. Increased apoptosis and inflammation was also observed after treatment with the PPAR\u03b3 antagonist GW9662. With chronic UVB irradiation, <jats:italic>Pparg<\/jats:italic>\u2212\/\u2212<jats:sup>epi<\/jats:sup> mice exhibited a sustained increase in erythema and transepidermal water loss relative to wildtype littermates. This suggests that PPAR\u03b3 agonists could have possible chemopreventive activity in non\u2010melanoma skin cancer.<\/jats:p>","DOI":"10.1002\/ijc.27562","type":"journal-article","created":{"date-parts":[[2012,4,3]],"date-time":"2012-04-03T13:24:47Z","timestamp":1333459487000},"source":"Crossref","is-referenced-by-count":29,"title":["Mice lacking epidermal PPAR\u03b3 exhibit a marked augmentation in photocarcinogenesis associated with increased UVB\u2010induced apoptosis, inflammation and barrier dysfunction"],"prefix":"10.1002","volume":"131","author":[{"given":"Ravi P.","family":"Sahu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia C.","family":"DaSilva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Badri","family":"Rashid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kellie 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