{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:08:39Z","timestamp":1777100919343,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"1-2","license":[{"start":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T00:00:00Z","timestamp":1590019200000},"content-version":"vor","delay-in-days":110,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA103830"],"award-info":[{"award-number":["R01 CA103830"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA185207"],"award-info":[{"award-number":["R01 CA185207"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE024392"],"award-info":[{"award-number":["R01 DE024392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Oral cancer causes significant global mortality and has a five\u2010year survival rate of around 64%. Poor prognosis results from late\u2010stage diagnosis, highlighting an important need to develop better approaches to detect oral premalignant lesions (OPLs) and identify which OPLs are at highest risk of progression to oral squamous cell carcinoma (OSCC). An appropriate animal model that reflects the genetic, histologic, immunologic, molecular and gross visual features of human OSCC would aid in the development and evaluation of early detection and risk assessment strategies. Here, we present an experimental<jats:italic>PIK3CA\u00a0+\u00a04NQO<\/jats:italic>transgenic mouse model of oral carcinogenesis that combines the PIK3CA oncogene mutation with oral exposure to the chemical carcinogen 4NQO, an alternate experimental transgenic mouse model with PIK3CA as well as E6 and E7 mutations, and an existing wild\u2010type mouse model based on oral exposure to 4NQO alone. We compare changes in dorsal and ventral tongue gross visual appearance, histologic features and molecular biomarker expression over a time course of carcinogenesis. Both transgenic models exhibit cytological and architectural features of dysplasia that mimic human disease and exhibit slightly increased staining for Ki\u201067, a cell proliferation marker. The PIK3CA\u00a0+\u00a04NQO model additionally exhibits consistent lymphocytic infiltration, presents with prominent dorsal and ventral tongue tumours, and develops cancer quickly relative to the other models. Thus, the PIK3CA\u00a0+\u00a04NQO model recapitulates the multistep genetic model of human oral carcinogenesis and host immune response in carcinogen\u2010induced tongue cancer, making it a useful resource for future OSCC studies.<\/jats:p>","DOI":"10.1111\/iep.12347","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T08:03:40Z","timestamp":1590048220000},"page":"45-54","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A PIK3CA transgenic mouse model with chemical carcinogen exposure mimics human oral tongue tumorigenesis"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9918-4062","authenticated-orcid":false,"given":"Melody T.","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Bioengineering Rice University Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean G.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences University of Texas School of Dentistry Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Luis","family":"Callejas\u2010Valera","sequence":"additional","affiliation":[{"name":"Cancer Biology Research Center Sanford Research Sioux Falls SD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann M.","family":"Gillenwater","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery M.D. Anderson Cancer Center University of Texas Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca R.","family":"Richards\u2010Kortum","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadarajah","family":"Vigneswaran","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences University of Texas School of Dentistry Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_7_3_1","unstructured":"HowladerN NooneAM KrapchoM et al. (2019)SEER Cancer Statistics Review (CSR) 1975\u20132016.Bethesda MD. Available at:https:\/\/seer.cancer.gov\/csr\/1975_2016\/(Accessed: 5 December 2018)."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coms.2014.01.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1758-7_37"},{"issue":"3","key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/ijc.28754","article-title":"Potentially malignant disorders of the oral cavity: Current practice and future directions in the clinic and laboratory","volume":"136","author":"Dionne KR","year":"2014","journal-title":"Int J 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