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To determine whether E-cadherin was a cause or consequence of OSE metaplasia, we expressed this cell-adhesion molecule in simian virus 40-immortalized OSE cells. In these cells the exogenous E-cadherin, all three catenins, and F-actin localized at sites of cell\u2013cell contact, indicating the formation of functional adherens junctions. Unlike the parent OSE cell line, which had undergone a typical mesenchymal transformation in culture, E-cadherin-expressing cells contained cytokeratins and the tight-junction protein occludin. They also formed cobblestone monolayers in two-dimensional culture and simple epithelia in three-dimensional culture that produced CA125 and shed it into the culture medium. CA125 is a normal epithelial-differentiation product of the oviduct, endometrium, and endocervix, but not of normal OSE. It is also a tumor antigen that is produced by ovarian neoplasms and by metaplastic OSE. Thus, E-cadherin restored some normal characteristics of OSE, such as keratin, and it also induced epithelial-differentiation markers associated with weakly preneoplastic, metaplastic OSE and OSE-derived primary carcinomas. The results suggest an unexpected role for E-cadherin in ovarian neoplastic progression.<\/jats:p>","DOI":"10.1073\/pnas.96.11.6249","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:52Z","timestamp":1027680052000},"page":"6249-6254","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":203,"title":["E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium"],"prefix":"10.1073","volume":"96","author":[{"given":"Nelly","family":"Auersperg","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC Canada V6H 3V5; Department of Anatomy, University of British Columbia, Vancouver, BC Canada V6T 1Z3; and Department of Anatomy and Cell Biology, University of North Dakota, Grand Forks, ND 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