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정재욱 (Jae-Wook Jeong) 저자 이메일 보기
서울대학교, Michigan State University
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조회 3274  인쇄하기 주소복사 트위터 공유 페이스북 공유 
β-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial–mesenchymal transition

Seo Jin Oh,1,2# Jung-Ho Shin,3# Tae Hoon Kim,1 Hee Sun Lee,4 Jung-Yoon Yoo,1 Ji Yeon Ahn,2 Russell R Broaddus,5 Makoto M Taketo,6 John P Lydon,7 Richard E Leach,1,8 Bruce A Lessey,9 Asgerally T Fazleabas,1,2 Jeong Mook Lim2 and Jae-Wook Jeong1,2*

1 Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, College of Human Medicine, Grand Rapids, MI 49503, USA
2 WCU Biomodulation Major, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea
3 Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Guro Hospital, Korea University Medical Centre, Seoul 152-703, Republic of Korea
4 Seoul Rachel Fertility Centre, Seoul 121-805, Republic of Korea
5 Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
6 Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Kono´e-cho, Sakyo, Kyoto 606.8501, Japan
7 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
8 Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group, Grand Rapids, MI 49503, USA
9 Department of Obstetrics and Gynecology, University Medical Group, Greenville Hospital System, Greenville, SC 29605, USA

*Correspondence to: J-W Jeong, Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, 333 Bostwick Avenue NE, Suite 4024, Grand Rapids, MI 49503, USA.

#These authors contributed equally to this study.
 
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 Ctnnb1f(ex3)/+ mice. Uteri of PRcre/+ Ctnnb1f(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 PRcre/+ Ctnnb1f(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 PRcre/+ Ctnnb1f(ex3)/+ mice but not in control mice. Vimentin and COUP-TFII, mesenchymal cell markers, were expressed in some epithelial cells of PRcre/+ Ctnnb1f(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.

Keywords: β-catenin; adenomyosis; epithelial-mesenchymal transition; uterus

논문정보 F1000선정
- 형식: Research article
- 게재일: 2013년 10월 (BRIC 등록일 2014-03-14)
- 연구진: 국내(교신)+국외 연구진태극기
- 분야: Pathology
- 추천: Faculty of 1000 Biology
- 추천사유: F1000Prime Recommendations, Dissents and Comments for [Oh SJ et al., J Pathol 2013, 231(2):210-22]. In F1000Prime, 13 Mar 2014; F1000Prime.com/718021608
광유전학의 과거, 현재와 미래[Neuron]
김윤석
발표: 김윤석 (Stanford University)
일자: 2020년 7월 30일 (목) 오후 02시 (한국시간)
언어: 한국어
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