S-Space College of Agriculture and Life Sciences (농업생명과학대학) Dept. of Agricultural Biotechnology (농생명공학부) Theses (Ph.D. / Sc.D._농생명공학부)
Studies on β-catenin Signaling in Adenomyosis Development through Epithelial-Mesenchymal Transition
- 농업생명과학대학 농생명공학부
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 농생명공학부, 2013. 8. 임정묵.
- Adenomyosis is a common gynecological disorder defined by the presence of endometrial glands and stromal within the myometrium. Despite its frequent occurrence, the precise etiology and physiopathology of adenomyosis is still unknown. WNT/β-catenin signaling molecules are important and should be tightly regulated for uterine function. Abnormal activation of β-catenin signaling by mutations in CTNNB1 is a causative factor of endometrial cancer. To investigate the role of β-catenin signaling in adenomyosis, the expression of β-catenin was examined in human adenomyosis by immunohistochemical analysis. The expression of nuclear and cytoplasmic β-catenin was significantly higher in epithelial cells of human adenomyosis compared to control endometrium. To determine if constitutive activation of β-catenin in the murine uterus leads to development of adenomyosis, mice were used which expressed a dominant stabilized β-catenin in the uterus by crossing the PR-Cre mouse with Ctnnb1f(ex3)/+ mice. Uteri of PRcre/+ Ctnnb1f(ex3)/+ mice display 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, which are transcriptional repressors of E-cadherin and an EMT marker, was observed in some epithelial cells of the uterusin PRcre/+ Ctnnb1f(ex3)/+ mice but not in control mice. Vimentin and COUP-TFII, mesenchymal cell markers, was 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, 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.