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?-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition.

ABSTRACT: Adenomyosis is defined by the presence of endometrial glands and stroma within the myometrium. Despite its frequent occurrence, the precise aetiology and physiopathology of adenomyosis is still unknown. WNT/?-catenin signalling molecules are important and should be tightly regulated for uterine function. To investigate the role of ?-catenin signalling in adenomyosis, the expression of ?-catenin was examined. Nuclear and cytoplasmic ?-catenin expression was significantly higher in epithelial cells of human adenomyosis compared to control endometrium. To determine whether constitutive activation of ?-catenin in the murine uterus leads to development of adenomyosis, mice that expressed a dominant stabilized ?-catenin in the uterus were used by crossing PR-Cre mice with Ctnnb1(f(ex3)/+) mice. Uteri of PR(cre) (/+) Ctnnb1(f(ex3)/+) mice displayed an abnormal irregular structure and highly active proliferation in the myometrium, and subsequently developed adenomyosis. Interestingly, the expression of E-cadherin was repressed in epithelial cells of PR(cre) (/+) Ctnnb1(f(ex3)/+) mice compared to control mice. Repression of E-cadherin is one of the hallmarks of epithelial-mesenchymal transition (EMT). The expression of SNAIL and ZEB1 was observed in some epithelial cells of the uterus in PR(cre) (/+) Ctnnb1(f(ex3)/+) mice but not in control mice. Vimentin and COUP-TFII, mesenchymal cell markers, were expressed in some epithelial cells of PR(cre) (/+) Ctnnb1(f(ex3)/+) mice. In human adenomyosis, the expression of E-cadherin was decreased in epithelial cells compared to control endometrium, while CD10, an endometrial stromal marker, was expressed in some epithelial cells of human adenomyosis. These results suggest that abnormal activation of ?-catenin contributes to adenomyosis development through the induction of EMT.

SUBMITTER: Oh SJ

PROVIDER: S-EPMC4105844 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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β-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition.

Oh Seo Jin SJ Shin Jung-Ho JH Kim Tae Hoon TH Lee Hee Sun HS Yoo Jung-Yoon JY Ahn Ji Yeon JY Broaddus Russell R RR Taketo Makoto M MM Lydon John P JP Leach Richard E RE Lessey Bruce A BA Fazleabas Asgerally T AT Lim Jeong Mook JM Jeong Jae-Wook JW

The Journal of pathology 20131001 2

Adenomyosis is defined by the presence of endometrial glands and stroma within the myometrium. Despite its frequent occurrence, the precise aetiology and physiopathology of adenomyosis is still unknown. WNT/β-catenin signalling molecules are important and should be tightly regulated for uterine function. To investigate the role of β-catenin signalling in adenomyosis, the expression of β-catenin was examined. Nuclear and cytoplasmic β-catenin expression was significantly higher in epithelial cell ...[more]

PMID: 23784889

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?-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition.

Publications

β-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition.

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