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EZH2 and Endometrial Cancer Development: Insights from a Mouse Model
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 delet...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909840/ https://www.ncbi.nlm.nih.gov/pubmed/35269532 http://dx.doi.org/10.3390/cells11050909 |
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author | Fang, Xin Ni, Nan Wang, Xiaofang Tian, Yanan Ivanov, Ivan Rijnkels, Monique Bayless, Kayla J. Lydon, John P. Li, Qinglei |
author_facet | Fang, Xin Ni, Nan Wang, Xiaofang Tian, Yanan Ivanov, Ivan Rijnkels, Monique Bayless, Kayla J. Lydon, John P. Li, Qinglei |
author_sort | Fang, Xin |
collection | PubMed |
description | 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 Pten(d/d); Ezh2(d/d) mice compared with that of Pten(d/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 Pten(d/d); Ezh2(d/d) mice during disease progression. Hence, these results reveal dual roles of EZH2 in endometrial cancer development. |
format | Online Article Text |
id | pubmed-8909840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89098402022-03-11 EZH2 and Endometrial Cancer Development: Insights from a Mouse Model Fang, Xin Ni, Nan Wang, Xiaofang Tian, Yanan Ivanov, Ivan Rijnkels, Monique Bayless, Kayla J. Lydon, John P. Li, Qinglei Cells Article 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 Pten(d/d); Ezh2(d/d) mice compared with that of Pten(d/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 Pten(d/d); Ezh2(d/d) mice during disease progression. Hence, these results reveal dual roles of EZH2 in endometrial cancer development. MDPI 2022-03-07 /pmc/articles/PMC8909840/ /pubmed/35269532 http://dx.doi.org/10.3390/cells11050909 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fang, Xin Ni, Nan Wang, Xiaofang Tian, Yanan Ivanov, Ivan Rijnkels, Monique Bayless, Kayla J. Lydon, John P. Li, Qinglei EZH2 and Endometrial Cancer Development: Insights from a Mouse Model |
title | EZH2 and Endometrial Cancer Development: Insights from a Mouse Model |
title_full | EZH2 and Endometrial Cancer Development: Insights from a Mouse Model |
title_fullStr | EZH2 and Endometrial Cancer Development: Insights from a Mouse Model |
title_full_unstemmed | EZH2 and Endometrial Cancer Development: Insights from a Mouse Model |
title_short | EZH2 and Endometrial Cancer Development: Insights from a Mouse Model |
title_sort | ezh2 and endometrial cancer development: insights from a mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909840/ https://www.ncbi.nlm.nih.gov/pubmed/35269532 http://dx.doi.org/10.3390/cells11050909 |
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