{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:37:39Z","timestamp":1776371859494,"version":"3.51.2"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T00:00:00Z","timestamp":1390435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutation or loss of the genes <jats:italic><jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic> have been implicated in human colorectal cancer (<jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content>), and have been shown to co\u2010occur despite both playing a role in the <jats:styled-content style=\"fixed-case\">PI3<\/jats:styled-content>' kinase (<jats:styled-content style=\"fixed-case\">PI3<\/jats:styled-content>'<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>) pathway. We investigated the role of these genes in intestinal tumour progression <jats:italic>in vivo<\/jats:italic>, using genetically engineered mouse models, with the aim of generating more representative models of human <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content>. Intestinal\u2010specific deletion of <jats:italic>Pten<\/jats:italic> and activation of an oncogenic allele of <jats:italic>Kras<\/jats:italic> was induced in wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) mice and mice with a predisposition to adenoma development (<jats:italic>Apc<jats:sup>fl\/+<\/jats:sup><\/jats:italic>). The animals were euthanized when they became symptomatic of a high tumour burden. Histopathological examination of the tissues was carried out, and immunohistochemistry used to characterize signalling pathway activation. Mutation of <jats:italic>Pten<\/jats:italic> and <jats:italic>Kras<\/jats:italic> resulted in a significant life\u2010span reduction of mice predisposed to adenomas. Invasive adenocarcinoma was observed in these animals, with evidence of activation of the <jats:styled-content style=\"fixed-case\">PI3<\/jats:styled-content>'<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content> pathway but no metastasis. However, mutation of <jats:italic>Pten<\/jats:italic> and <jats:italic>Kras<\/jats:italic> in <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> animals not predisposed to adenomas led to perturbed homeostasis of the intestinal epithelium and the development of hyperplastic polyps, dysplastic sessile serrated adenomas and metastasizing adenocarcinomas with serrated features. These studies demonstrate synergism between <jats:italic>Pten<\/jats:italic> and <jats:italic>Kras<\/jats:italic> mutations in intestinal tumour progression, in an autochthonous and immunocompetent murine model, with potential application to preclinical drug testing. In particular, they show that <jats:italic>Pten<\/jats:italic> and <jats:italic>Kras<\/jats:italic> mutations alone predispose mice to the spectrum of serrated lesions that reflect the serrated pathway of <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content> progression in humans. Published by John Wiley &amp; Sons, Ltd. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.pathsoc.org.uk\">www.pathsoc.org.uk<\/jats:ext-link><\/jats:p>","DOI":"10.1002\/path.4312","type":"journal-article","created":{"date-parts":[[2013,11,29]],"date-time":"2013-11-29T10:29:08Z","timestamp":1385720948000},"page":"27-38","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["<i><scp>PTEN<\/scp><\/i> loss and <i><scp>KRAS<\/scp><\/i> activation leads to the formation of serrated adenomas and metastatic carcinoma in the mouse intestine"],"prefix":"10.1002","volume":"233","author":[{"given":"Emma J","family":"Davies","sequence":"first","affiliation":[{"name":"Cardiff School of Biosciences Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Marsh Durban","sequence":"additional","affiliation":[{"name":"Cardiff School of Biosciences 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