{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:00:42Z","timestamp":1791918042361,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T00:00:00Z","timestamp":1363219200000},"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":[[2013,5]]},"abstract":"Abstract<\/jats:title>\n \n \n Endometrioid endometrial cancer arises through a gradual series of histological changes, each accompanied by specific alterations in gene expression and activity. Activation of the Wnt\u2013\n \u03b2<\/jats:italic>\n \u2010catenin pathway and loss of\n PTEN<\/jats:styled-content>\n activity are frequently observed in endometrial cancers. However, the specific roles played by alterations in these pathways in the initiation and progression of endometrial cancer are currently unclear. Here, we investigated the effects of loss of\n Pten<\/jats:italic>\n and\n Apc<\/jats:italic>\n gene function in the mouse endometrium by employing tissue\u2010specific and inducible mutant alleles, followed by immunohistochemical (\n IHC<\/jats:styled-content>\n ) and loss of heterozygosity (\n LOH<\/jats:styled-content>\n ) analysis of their corresponding cancerous lesions. Loss of the\n Apc<\/jats:italic>\n function in the endometrium leads to cytoplasmic and nuclear\n \u03b2<\/jats:italic>\n \u2010catenin accumulation in association with uterine hyperplasia and squamous cell metaplasia, but without malignant transformation. Loss of\n Pten<\/jats:italic>\n function also resulted in squamous metaplasia but, in contrast to loss of\n Apc<\/jats:italic>\n function, it initiates endometrial cancer. On the other hand, loss of\n Apc<\/jats:italic>\n function in the endometrium accelerates\n Pten<\/jats:italic>\n \u2010driven endometrial tumourigenesis. Analysis of compound heterozygous mice confirmed that somatic loss of the wild\u2010type\n Pten<\/jats:italic>\n allele represents the rate\u2010limiting initiation step in endometrial cancer. Simultaneous loss of\n Pten<\/jats:italic>\n and\n Apc<\/jats:italic>\n resulted in endometrial cancer characterized by earlier onset and a more aggressive malignant behaviour. These observations are indicative of the synergistic action between the Wnt\u2013\n \u03b2<\/jats:italic>\n \u2010catenin and Pten signalling pathways in endometrial cancer onset and progression. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:bold>\n <\/jats:p>","DOI":"10.1002\/path.4160","type":"journal-article","created":{"date-parts":[[2013,1,3]],"date-time":"2013-01-03T09:38:49Z","timestamp":1357205929000},"page":"48-58","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Alterations in Wnt\u2013\n \u03b2<\/i>\n \u2010catenin and Pten signalling play distinct roles in endometrial cancer initiation and progression"],"prefix":"10.1002","volume":"230","author":[{"given":"Marten","family":"van der Zee","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology Erasmus MC University Medical Centre Rotterdam The Netherlands"},{"name":"Department of Pathology Erasmus MC University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yundan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Erasmus MC University Medical Centre Rotterdam The Netherlands"},{"name":"Department of Pathology Erasmus MC University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Erasmus MC University Medical Centre Rotterdam The Netherlands"},{"name":"Department of Pathology Erasmus MC University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Heijmans\u2010Antonissen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Erasmus MC University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia C","family":"Ewing","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus MC University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Franken","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus MC University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco J","family":"DeMayo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P","family":"Lydon","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curt W","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Erasmus MC University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Fodde","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus MC University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen J","family":"Blok","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Erasmus MC University Medical Centre Rotterdam The 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