{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T11:56:24Z","timestamp":1792410984668,"version":"4.4.0"},"reference-count":79,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007904","name":"Texas A&amp;M University","doi-asserted-by":"publisher","award":["T3 grant"],"award-info":[{"award-number":["T3 grant"]}],"id":[{"id":"10.13039\/100007904","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD087236"],"award-info":[{"award-number":["R01HD087236"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R24HD102061"],"award-info":[{"award-number":["R24HD102061"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI152050"],"award-info":[{"award-number":["R21AI152050"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Enhancer of zeste homolog 2 (EZH2), a core component of polycomb repressive complex 2, plays an important role in cancer development. As both oncogenic and tumor suppressive functions of EZH2 have been documented in the literature, the objective of this study is to determine the impact of Ezh2 deletion on the development and progression of endometrial cancer induced by inactivation of phosphatase and tensin homolog (PTEN), a tumor suppressor gene frequently dysregulated in endometrial cancer patients. To this end, we created mice harboring uterine deletion of both Ezh2 and Pten using Cre recombinase driven by the progesterone receptor (Pgr) promoter. Our results showed reduced tumor burden in Ptend\/d; Ezh2d\/d mice compared with that of Ptend\/d mice during early carcinogenesis. The decreased Ki67 index in EZH2 and PTEN-depleted uteri versus that in PTEN-depleted uteri indicated an oncogenic role of EZH2 during early tumor development. However, mice harboring uterine deletion of both Ezh2 and Pten developed unfavorable disease outcome, accompanied by exacerbated epithelial stratification and heightened inflammatory response. The observed effect was non-cell autonomous and mediated by altered immune response evidenced by massive accumulation of intraluminal neutrophils, a hallmark of endometrial carcinoma in Ptend\/d; Ezh2d\/d mice during disease progression. Hence, these results reveal dual roles of EZH2 in endometrial cancer development.<\/jats:p>","DOI":"10.3390\/cells11050909","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T10:21:16Z","timestamp":1646648476000},"page":"909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["EZH2 and Endometrial Cancer Development: Insights from a Mouse Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Xin","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Rijnkels","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla J.","family":"Bayless","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, 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 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. 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