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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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Project description:BackgroundCigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated.MethodsThe present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT.ResultsBased on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling.ConclusionsIn summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

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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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