{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:00:24Z","timestamp":1760403624934,"version":"build-2065373602"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,4,9]],"date-time":"2013-04-09T00:00:00Z","timestamp":1365465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:p><jats:styled-content>Background:<\/jats:styled-content> The transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) signaling pathway is generally believed to be a potent inhibitor of proliferation. However, many epithelia lacking the essential <jats:italic>Tgfbr2<\/jats:italic> gene still maintain normal tissue homeostasis. Here, transgenic mice expressing <jats:italic>rtTA<\/jats:italic> from the human <jats:italic>keratin 14<\/jats:italic> (<jats:italic>K14<\/jats:italic>) promoter were used to generate an inducible dominant\u2010negative TGF\u2010\u03b2 receptor type II (Tgfbr2) mutant model, which allowed us to distinguish between the primary and secondary effects of TGF\u2010\u03b2 signaling disruption by Doxycycline treatment in K14+ epithelial stem cells. <jats:styled-content>Results:<\/jats:styled-content> We showed that in mice lacking TGF\u2010\u03b2 signaling in K14+ cells, invasive carcinomas developed on the ventral surface of the tip of the tongue, while filiform papillae on the dorsal surface showed different pathological changes from the tip to the posterior of the tongue. In addition, acetylation levels of histone H4 and histone H3 rapidly increased, while pMAPK activity was enhanced and Jagged2 inactivated in lingual epithelia after disruption of TGF\u2010\u03b2 signaling. <jats:styled-content>Conclusions:<\/jats:styled-content> Our results contribute to the understanding of TGF\u2010\u03b2 signaling in regulating homeostasis and carcinogenesis in lingual epithelia. <jats:italic>Developmental Dynamics 242:444\u2013455, 2013<\/jats:italic>. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.23933","type":"journal-article","created":{"date-parts":[[2013,1,30]],"date-time":"2013-01-30T04:36:44Z","timestamp":1359520604000},"page":"444-455","source":"Crossref","is-referenced-by-count":3,"title":["Conditional expression of the dominant\u2010negative TGF\u2010\u03b2 receptor type II elicits lingual epithelial hyperplasia in transgenic 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