期刊
JOURNAL OF PATHOLOGY
卷 222, 期 3, 页码 261-270出版社
WILEY
DOI: 10.1002/path.2761
关键词
adenomyosis; endometrial epithelial cells; epithelial-mesenchymal transition; oestrogen; Slug
资金
- National Science Council [96-2314-B-075-013, 97-2314-B-010-003]
- Taipei Veterans General Hospital [98-C1-167, 99-C1-166, 98-A-093, 99-A-065, 98-C1-050, 98-ER2-008, 99-C1-077, 99-ER2-007]
- Yen-Tjing-Ling Medical Foundation [C1-97-6]
- Ministry of Education, Aim for the Top University Plan [97A-C-T510, 97A-C-P405, 98A-C-T510]
- Department of Health, Center of Excellence for Cancer Research at the Taipei Veterans General Hospital [DOH99-TD-C-111-007]
Adenomyosis is an oestrogen-dependent disease caused by a downward extension of the endometrium into the uterine myometrium. Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties and can be induced by oestrogen. We hypothesized that oestrogen-induced EMT is critical in the pathogenesis of adenomyosis. We first investigated whether EMT occurred in adenomyotic lesions and whether it correlated with serum 17 beta-oestradiol (E2) levels. Immunohistochemistry was performed on adenomyotic lesions and corresponding eutopic endometrium samples from women with adenomyosis. Endometria from women without endometrial disorders were used as a control. In the epithelial component of adenomyotic lesions, vimentin expression was up-regulated and E-cadherin expression was down-regulated compared to the eutopic endometrium, suggesting that EMT occurs in adenomyosis. In adenomyosis, the serum E2 level was negatively correlated with E-cadherin expression in the epithelial components of the eutopic endometrium and adenomyotic lesions, suggesting the involvement of oestrogen-induced EMT in endometrial cells. In oestrogen receptor-positive Ishikawa endometrial epithelial cells, oestrogen induced a morphological change to a fibroblast-like phenotype, a shift from epithelial marker expression to mesenchymal marker expression, increased migration and invasion, and up-regulation of the EMT regulator Slug. Raloxifene, a selective oestrogen receptor modulator, abrogated these effects. To determine the role of oestrogen-induced EMT in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium or adenomyotic lesions from adenomyosis patients into ovariectomized SCID mice. The implantation of endometrium was oestrogen-dependent and was suppressed by raloxifene. Collectively, these data highlight the crucial role of oestrogen-induced EMT in the development of adenomyosis and suggest that raloxifene may be a potential therapeutic agent for adenomyosis patients. (C) Copyright 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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