title: β-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/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.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, College of Human Medicine, Grand Rapids, MI, 49503, USA; WCU Biomodulation Major, College of Agriculture and Life Sciences, Seoul National University, Seoul, 151-742, Republic of Korea.
authors.forename: Seo Jin
authors.initials: SJ
authors.lastname: Oh
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Yoo
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Ahn
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.forename: Richard E
authors.initials: RE
authors.lastname: Leach
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
authors.forename: Asgerally T
authors.initials: AT
authors.lastname: Fazleabas
authors.forename: Jeong Mook
authors.initials: JM
authors.lastname: Lim
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
mesh_terms: D062788:Adenomyosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin
keywords: adenomyosis; epithelial-mesenchymal transition; uterus; β-catenin