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An estrogen-induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations.

ABSTRACT: Endometrial hyperplasia (EH) is a condition originating from uterine endometrial glands undergoing disordered proliferation including the risk to progress to endometrial adenocarcinoma. In recent years, a steady increase in EH cases among younger women of reproductive age accentuates the demand of therapeutic alternatives, which emphasizes that an improved disease model for therapeutic agents evaluation is concurrently desired. Here, a new hormone-induced EH mouse model was developed using a subcutaneous estradiol (E2)-sustained releasing pellet, which elevates the serum E2 level in mice, closely mimicking the effect known as estrogen dominance with underlying, pathological E2 levels in patients. The onset and progression of EH generated within this model recapitulate a clinically relevant, pathological transformation, beginning with disordered proliferation developing to simple EH, advancing to atypical EH, and then progressing to precancerous stages, all following a chronologic manner. Although a general increase in nuclear progesterone receptor (PR) expression occurred after E2 expression, a total loss in PR was noted in some endometrial glands as disease advanced to simple EH. Furthermore, estrogen receptor (ER) expression in the nucleus of endometrial cells was reduced in disordered proliferation and increased when EH progressed to atypical EH and precancerous stages. This EH model also resembles other pathological patterns found in human disease such as leukocytic infiltration, genetic aberrations in ?-catenin, and joint phosphatase and tensin homolog/paired box gene 2 (PTEN/PAX2) silencing. In summary, this new and comprehensively characterized EH model is cost-effective, easily reproducible, and may serve as a tool for preclinical testing of therapeutic agents and facilitate further investigation of EH.

SUBMITTER: Yang CH

PROVIDER: S-EPMC4529342 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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An estrogen-induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations.

Yang Chieh-Hsiang CH Almomen Aliyah A Wee Yin Shen YS Jarboe Elke A EA Peterson C Matthew CM Janát-Amsbury Margit M MM

Cancer medicine 20150323 7

Endometrial hyperplasia (EH) is a condition originating from uterine endometrial glands undergoing disordered proliferation including the risk to progress to endometrial adenocarcinoma. In recent years, a steady increase in EH cases among younger women of reproductive age accentuates the demand of therapeutic alternatives, which emphasizes that an improved disease model for therapeutic agents evaluation is concurrently desired. Here, a new hormone-induced EH mouse model was developed using a sub ...[more]

PMID: 25809780

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An estrogen-induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations.

Publications

An estrogen-induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations.

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