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The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression

Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. An additional endometrial cancer mouse model is generated by ablation of Pten (either as heterozygotes or by conditional uterine ablation). To determine the interplay b...

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Autores principales: Kim, Tae Hoon, Franco, Heather L., Jung, Sung Yun, Qin, Jun, Broaddus, Russell R., Lydon, John P., Jeong, Jae-Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013686/
https://www.ncbi.nlm.nih.gov/pubmed/20418913
http://dx.doi.org/10.1038/onc.2010.126
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author Kim, Tae Hoon
Franco, Heather L.
Jung, Sung Yun
Qin, Jun
Broaddus, Russell R.
Lydon, John P.
Jeong, Jae-Wook
author_facet Kim, Tae Hoon
Franco, Heather L.
Jung, Sung Yun
Qin, Jun
Broaddus, Russell R.
Lydon, John P.
Jeong, Jae-Wook
author_sort Kim, Tae Hoon
collection PubMed
description Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. An additional endometrial cancer mouse model is generated by ablation of Pten (either as heterozygotes or by conditional uterine ablation). To determine the interplay between Mig-6 and the PTEN/PI3K signaling pathway during endometrial tumorigenesis, we have generated mice with Mig-6 and Pten conditionally ablated in progesterone receptor positive cells (PR(cre/+)Mig-6(f/f)Pten(f/f) ; Mig-6(d/d)Pten(d/d)). The ablation of both Mig-6 and Pten dramatically accelerated the development of endometrial cancer compared to single ablation of either gene. The epithelium of Mig-6(d/d)Pten(d/d) mice showed a significant decrease in the number of apoptotic cells compared to Pten(d/d) mice. The expression of the estrogen-induced apoptotic inhibitors Birc1 was significantly increased in the Mig-6(d/d)Pten(d/d) mice. We identified ERK2 as a MIG-6 interacting protein by co-immunoprecipitation and demonstrated that the level of ERK2 phosphorylation was increased upon Mig-6 ablation either singly or in combination with Pten ablation. These results suggest that Mig-6 exerts a tumor suppressor function in endometrial cancer by promoting epithelial cell apoptosis through the down-regulation of the estrogen-induced apoptosis inhibitors Birc1 and the inhibition of ERK2 phosphorylation.
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spelling pubmed-40136862014-05-08 The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression Kim, Tae Hoon Franco, Heather L. Jung, Sung Yun Qin, Jun Broaddus, Russell R. Lydon, John P. Jeong, Jae-Wook Oncogene Article Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. An additional endometrial cancer mouse model is generated by ablation of Pten (either as heterozygotes or by conditional uterine ablation). To determine the interplay between Mig-6 and the PTEN/PI3K signaling pathway during endometrial tumorigenesis, we have generated mice with Mig-6 and Pten conditionally ablated in progesterone receptor positive cells (PR(cre/+)Mig-6(f/f)Pten(f/f) ; Mig-6(d/d)Pten(d/d)). The ablation of both Mig-6 and Pten dramatically accelerated the development of endometrial cancer compared to single ablation of either gene. The epithelium of Mig-6(d/d)Pten(d/d) mice showed a significant decrease in the number of apoptotic cells compared to Pten(d/d) mice. The expression of the estrogen-induced apoptotic inhibitors Birc1 was significantly increased in the Mig-6(d/d)Pten(d/d) mice. We identified ERK2 as a MIG-6 interacting protein by co-immunoprecipitation and demonstrated that the level of ERK2 phosphorylation was increased upon Mig-6 ablation either singly or in combination with Pten ablation. These results suggest that Mig-6 exerts a tumor suppressor function in endometrial cancer by promoting epithelial cell apoptosis through the down-regulation of the estrogen-induced apoptosis inhibitors Birc1 and the inhibition of ERK2 phosphorylation. 2010-04-26 2010-07-01 /pmc/articles/PMC4013686/ /pubmed/20418913 http://dx.doi.org/10.1038/onc.2010.126 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Kim, Tae Hoon
Franco, Heather L.
Jung, Sung Yun
Qin, Jun
Broaddus, Russell R.
Lydon, John P.
Jeong, Jae-Wook
The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression
title The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression
title_full The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression
title_fullStr The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression
title_full_unstemmed The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression
title_short The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression
title_sort synergistic effect of mig-6 and pten ablation on endometrial cancer development and progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013686/
https://www.ncbi.nlm.nih.gov/pubmed/20418913
http://dx.doi.org/10.1038/onc.2010.126
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