Linked Life Data

19439667

Source:http://linkedlifedata.com/resource/pubmed/id/19439667

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pubmed-article:19439667pubmed:abstractTextNormal endometrial function requires a balance of progesterone (P4) and estrogen (E2) effects. An imbalance caused by increased E2 action and/or decreased P4 action can result in abnormal endometrial proliferation and, ultimately, endometrial adenocarcinoma, the fourth most common cancer in women. We have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of progesterone receptor (PR) and steroid receptor coactivator (SRC-1) action in the uterus. Here, we demonstrate that absence of Mig-6 in mice results in the inability of P4 to inhibit E2-induced uterine weight gain and E2-responsive target genes expression. At 5 months of age, the absence of Mig-6 results in endometrial hyperplasia. Ovariectomized Mig-6(d/d) mice exhibit this hyperplastic phenotype in the presence of E2 and P4 but not without ovarian hormone. Ovariectomized Mig-6(d/d) mice treated with E2 developed invasive endometrioid-type endometrial adenocarcinoma. Importantly, the observation that endometrial carcinomas from women have a significant reduction in MIG-6 expression provides compelling support for an important growth regulatory role for Mig-6 in the uterus of both humans and mice. This demonstrates the Mig-6 is a critical regulator of the response of the endometrium to E2 in regulating tissue homeostasis. Since Mig-6 is regulated by both PR and SRC-1, this identifies a PR, SRC-1, Mig-6 regulatory pathway that is critical in the suppression of endometrial cancer.lld:pubmed
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pubmed-article:19439667pubmed:authorpubmed-author:GiudiceLinda...lld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:LesseyBruce...lld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:TsaiSophia...lld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:ZhangYu-WenYWlld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:Vande...lld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:YoungSteven...lld:pubmed
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pubmed-article:19439667pubmed:authorpubmed-author:LydonJohn PJPlld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:WhiteLisa DLDlld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:LeeHee SunHSlld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:LeeKevin YKYlld:pubmed
pubmed-article:19439667pubmed:authorpubmed-author:JeongJae-Wook...lld:pubmed
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