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Role of E-cadherin in the serous borderline ovarian tumor and low-grade serous ovarian carcinoma cell invasion

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dc.contributor.author Cheng, Jung-Chien
dc.date.accessioned 2012-12-05T19:48:33Z
dc.date.available 2012-12-05T19:48:33Z
dc.date.copyright 2012 en
dc.date.issued 2012-12-05
dc.identifier.uri http://hdl.handle.net/2429/43651
dc.description.abstract E-cadherin is a membrane glycoprotein located at cell adherens junctions. A switch from E-cadherin to N-cadherin expression has been considered a hallmark of the epithelial-mesenchymal transition (EMT), which is primarily due to the up-regulation of the transcription factors Snail, Slug, Twist and ZEB1. Epithelial ovarian cancer cells with low E-cadherin expression are more invasive, and the absence of E-cadherin expression in ovarian cancer is associated with poor prognosis and survival. Serous borderline ovarian tumors (SBOT) are slow-growing, non-invasive ovarian epithelial neoplasms. SBOT are considered distinct entities that give rise to invasive low-grade serous carcinomas (LGSC), which have a relatively poor prognosis and are unrelated to high-grade serous carcinomas (HGSC). The mechanisms underlying the progression of non-invasive SBOT to invasive LGSC are not understood. We have established short-term cultures of SBOT cells from tumor biopsies and have shown that inactivation of p53, Rb and/or PP2A by the SV40 large T (LT) and small T (ST) antigens allows SBOT cells to acquire characteristics associated with neoplastic progression, including increased cell motility, invasion and EMT. However, the overexpression of N-cadherin does not induce cell invasion in SBOT cells. In this study, using loss- and gain-of-function approaches, we show that p53 acts as a tumor suppressor in the regulation of SBOT and LGSC cell invasion by regulating E-cadherin expression through PI3K/Akt-mediated transcriptional and epigenetic machineries. In high-grade ovarian cancer cultures, it has been shown that epidermal growth factor (EGF) and transforming growth factor-beta (TGF-β) induce cell invasion by activating the EMT. However, the effects of EGF and TGF-β on SBOT and LGSC cell invasion remain unknown. We show that EGF induces SBOT cell invasion by activating the EMT. In addition, our results suggest that there are EMT-independent mechanisms that mediate EGF-induced LGSC cell invasion. Interestingly, we show a dual function for TGF-β in which it induces invasion in SBOT cells by activating the EMT and promotes apoptosis in LGSC cells. Overall, this study demonstrates that the loss of E-cadherin expression in SBOT may play an important role in the transition to invasive LGSC. en
dc.language.iso eng en
dc.publisher University of British Columbia en
dc.relation.ispartof Electronic Theses and Dissertations (ETDs) 2008+ en
dc.title Role of E-cadherin in the serous borderline ovarian tumor and low-grade serous ovarian carcinoma cell invasion en
dc.type Text en
dc.degree.name Doctor of Philosophy - PhD en
dc.degree.discipline Reproductive and Developmental Sciences en
dc.degree.grantor University of British Columbia en
dc.date.graduation 2013-05 en
dc.type.text Thesis/Dissertation en
dc.description.affiliation Medicine, Faculty of
dc.degree.campus UBCV en
dc.description.scholarlevel Graduate en

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