{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:21:07Z","timestamp":1791310867702,"version":"4.3.1"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,8,17]]},"abstract":"<jats:p>\n                    Activator protein-1 (AP-1) is a transcription factor that consists of either a Jun-Jun homodimer or a Jun-Fos heterodimer. Transactivation of AP-1 is required for tumor promoter-induced transformation in mouse epidermal JB6 cells and for progression in mouse and human keratinocytes. Until now, the question of whether AP-1 transactivation is required for carcinogenesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    has remained unanswered, as has the issue of functionally significant target genes. To address these issues we have generated a transgenic mouse in which transactivation mutant\n                    <jats:italic>c-jun<\/jats:italic>\n                    (TAM67), under the control of the human keratin-14 promoter, is expressed specifically in the basal cells of the epidermis where tumor induction is initiated. The keratin-14\u2013TAM67 transgene was expressed in the epidermis, tongue, and cervix, with no apparent abnormalities in any tissue or organ. TAM67 expression blocked 12-\n                    <jats:italic>O<\/jats:italic>\n                    -tetradecanoylphorbol 13-acetate (TPA, phorbol 12-tetradecanoate 13-acetate) induction of the AP-1-regulated luciferase in AP-1 luciferase\/TAM67 mice, but did not inhibit induction of candidate AP-1 target genes, collagenase-1 or stromelysin-3. More interestingly, TAM67 expression did not inhibit TPA-induced hyperproliferation. In two-stage skin carcinogenesis experiments, the transgenic animals showed a dramatic inhibition of papilloma induction. We conclude that transactivation of a subset of AP-1-dependent genes is required for tumor promotion and may be targeted for cancer prevention.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.17.9827","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"9827-9832","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":321,"title":["Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion"],"prefix":"10.1073","volume":"96","author":[{"given":"Matthew R.","family":"Young","sequence":"first","affiliation":[{"name":"Basic Research Laboratory and Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute, Frederick, MD 21702; Transgenic Mouse Facility, National Institute of Allergy and Infectious Diseases, Frederick, MD 21702; Department of Medicine, Program of Immunobiology, University of Vermont, Burlington, VT 05405; and Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory and Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute, Frederick, MD 21702; Transgenic Mouse Facility, National Institute of Allergy and Infectious Diseases, Frederick, MD 21702; Department of Medicine, Program of Immunobiology, University of Vermont, Burlington, VT 05405; and Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Rinc\u00f3n","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory and Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute, Frederick, MD 21702; Transgenic Mouse Facility, National Institute of Allergy and Infectious Diseases, Frederick, MD 21702; Department of Medicine, Program of Immunobiology, University of Vermont, Burlington, VT 05405; and Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory and Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute, Frederick, MD 21702; Transgenic Mouse Facility, National Institute of Allergy and Infectious Diseases, Frederick, MD 21702; Department of Medicine, Program of Immunobiology, University of Vermont, Burlington, VT 05405; and Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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