{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T16:10:26Z","timestamp":1700064626192},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,1,11]],"date-time":"2007-01-11T00:00:00Z","timestamp":1168473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Elevated polyamine content and increased ornithine decarboxylase (ODC) activity have been associated with neoplastic growth in numerous animal models and human tissues. Antizyme (AZ) is a negative regulator of polyamine metabolism that inhibits ODC activity, stimulates ODC degradation, and suppresses polyamine uptake. Preliminary evidence, obtained from transgenic mice with tissue specific overexpression of AZ indicates that tumor development can be suppressed by AZ. To extend these studies, we have examined the effect of keratin 5 (K5)\u2010 or K6\u2010driven AZ transgenes on 7,12\u2010dimethylbenz[a]anthracene (DMBA)\/12\u2010<jats:italic>O<\/jats:italic>\u2010tetradecanoylphorbol\u201013\u2010acetate (TPA) chemical carcinogenesis of the skin, in promotion\u2010resistant C57BL\/6 and promotion\u2010sensitive DBA\/2 mice. On both genetic backgrounds, K6\u2010AZ mice showed a reduction in tumor multiplicity, with 85% fewer tumors than wild\u2010type controls on the C57BL\/6 background and 50% fewer tumors on the DBA\/2 background. K5\u2010AZ mice developed 50% fewer tumors than controls on both backgrounds. The percent of mice with tumors and tumor size were also reduced in the K5\u2010AZ and K6\u2010AZ groups. Tumor and TPA\u2010treated skin sections from K6\u2010AZ mice exhibited the strongest AZ expression, with localization mainly in suprabasal keratinocytes. K6\u2010AZ mice also had slightly reduced cell proliferation rates in tumors and TPA\u2010treated skin. The lack of a more pronounced effect on cell proliferation is probably explained by the observation that AZ staining did not colocalize with proliferating cell nuclear antigen (PCNA), a marker for the proliferative compartment. These studies demonstrate a tumor\u2010suppressive effect of AZ in C57BL\/6 and DBA\/2 mice, and confirm the importance of ODC and polyamines in tumor development. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20294","type":"journal-article","created":{"date-parts":[[2007,1,11]],"date-time":"2007-01-11T22:54:27Z","timestamp":1168556067000},"page":"453-465","source":"Crossref","is-referenced-by-count":17,"title":["Mouse skin chemical carcinogenesis is inhibited by antizyme in promotion\u2010sensitive and promotion\u2010resistant genetic backgrounds"],"prefix":"10.1002","volume":"46","author":[{"given":"David J.","family":"Feith","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa M.","family":"Shantz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula 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