Abstract
Abstract The cellular and molecular mechanisms that underlie promotion by diverse tumor promoting agents remain to be fully elucidated. Studies using Stat1 knockout (KO) mice have shown that they were highly resistant to two-stage skin carcinogenesis using chrysarobin as the promoter. In contrast, Stat1 KO mice treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) as the tumor promoter exhibited no significant differences in tumor formation. To further investigate mechanism(s) whereby Stat1 mediates skin tumor promotion by chrysarobin Stat1 KO mice and wild-type (WT) controls were treated with the respective tumor promoters and Stat1-dependent signaling pathways were evaluated. Mice deficient in Stat1 displayed an attenuated induction of epidermal Cox-2 mRNA and protein as well as reduced PGE2 levels compared to WT controls following topical application of chrysarobin, whereas, mice treated with TPA exhibited no significant differences in Cox-2 levels or PGE2 levels. Other results also suggest that Stat1 may regulate various cytokine/chemokines involved in the inflammatory response following chrysarobin treatment. Preliminary experiments have also shown that Stat1 KO mice exhibit reduced induction of interferon regulatory factor-1 (IRF-1) following chrysarobin treatment, compared to WT controls. In contrast, treatment with TPA caused no significant differences in expression of IRF-1. Collectively, these findings suggest that chrysarobin may elicit a Stat1-dependent signaling response that is dependent on IRF-1, whereas TPA-mediated tumorigenesis is independent of this signaling pathway. These and other ongoing studies aimed at characterizing the role of Stat1 and IRF-1 signaling in chrysarobin-mediated tumor promotion will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2556. doi:1538-7445.AM2012-2556
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