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β ‐Catenin activation contributes to the pathogenesis of adenomyosis through epithelial–mesenchymal transition
Author(s) -
Oh Seo Jin,
Shin JungHo,
Kim Tae Hoon,
Lee Hee Sun,
Yoo JungYoon,
Ahn Ji Yeon,
Broaddus Russell R,
Taketo Makoto M,
Lydon John P,
Leach Richard E,
Lessey Bruce A,
Fazleabas Asgerally T,
Lim Jeong Mook,
Jeong JaeWook
Publication year - 2013
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4224
Subject(s) - adenomyosis , myometrium , endometrium , catenin , wnt signaling pathway , mesenchymal stem cell , epithelial–mesenchymal transition , vimentin , stromal cell , biology , cadherin , immunohistochemistry , pathology , cancer research , uterus , microbiology and biotechnology , endocrinology , signal transduction , medicine , cell , transition (genetics) , gene , biochemistry , genetics
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 / 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 cells of human adenomyosis compared to control endometrium. To determine whether constitutive activation of β ‐catenin in the murine uterus leads to development of adenomyosis, mice that expressed a dominant stabilized β ‐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 β ‐catenin contributes to adenomyosis development through the induction of EMT . Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.