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- W4361265849 abstract "<div>Abstract<p>Activation of activator protein 1 (AP-1) and nuclear factor κB (NFκB)–dependent transcription is required for tumor promotion in cell culture models and transgenic mice. Dominant-negative c-Jun (TAM67) blocks AP-1 activation by dimerizing with Jun or Fos family proteins and blocks NFκB activation by interacting with NFκB p65. Two-stage [7,12-dimethylbenz(<i>a</i>)anthracene (DMBA)/12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA)] skin carcinogenesis experiments in a model relevant to human cancer risk, transgenic mice expressing human papillomavirus 16 E7 oncogene (K14-HPV16-E7), show E7-enhanced tumor promotion. A cross to K14-TAM67–expressing mice results in dramatic inhibition of tumor promoter–induced AP-1 luciferase reporter activation and papillomagenesis. Epithelial specific TAM67 expression inhibits tumorigenesis without affecting TPA- or E7-induced hyperproliferation of the skin. Thus, the mouse model enriches for TAM67 targets relevant to tumorigenesis rather than to general cell proliferation or hyperplasia, implicating a subset of AP-1– and/or NFκB-dependent genes. The aim of the present study was to identify target genes responsible for TAM67 inhibition of DMBA-TPA–induced tumorigenesis. Microarray expression analysis of epidermal tissues revealed small sets of genes in which expression is both up-regulated by tumor promoter and down-regulated by TAM67. Among these, cyclooxygenase-2 (Cox-2/Ptgs2) and osteopontin (Opn/Spp1) are known to be functionally significant in driving carcinogenesis. Results identify both Cox-2 and Opn as transcriptional targets of TAM67 with CRE, but not NFκB sites important in the Cox-2 promoter and an AP-1 site important in the Opn promoter. [Cancer Res 2007;67(6):2430–8]</p></div>" @default.
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- W4361265849 date "2023-03-30" @default.
- W4361265849 modified "2023-09-30" @default.
- W4361265849 title "Data from Dominant-Negative Activator Protein 1 (TAM67) Targets Cyclooxygenase-2 and Osteopontin under Conditions in which It Specifically Inhibits Tumorigenesis" @default.
- W4361265849 doi "https://doi.org/10.1158/0008-5472.c.6494877" @default.
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