The EMT­activator ZEB1 is unrelated to platinum drug resistance in ovarian cancer but predictive of survival

Rae, Sophie, Keenan, Joanne, Spillane, Cathy, Blackshields, Gordon, Madden, Stephen and Stordal, Britta K. ORCID: https://orcid.org/0000-0002-7892-951X (2015) The EMT­activator ZEB1 is unrelated to platinum drug resistance in ovarian cancer but predictive of survival. In: 2015 NCRI Cancer Conference, 01-03 Nov 2015, Liverpool, UK. . [Conference or Workshop Item]

PDF - Final accepted version (with author's formatting) Restricted to Repository staff and depositor only Available under License Creative Commons Attribution 4.0. Download (884kB)

Abstract

Background: We have previously shown that IGROVCDDP cells model the resistance phenotype of ovarian cancer patients who have failed platinum/taxane chemotherapy. In this study we show that IGROVCDDP have also undergone epithelial­-mesenchymal transition (EMT). We aim to determine if alterations in EMT-­related genes are related to the drug­-resistance phenotype.
Method: EMT markers, invasion, motility and morphology of the IGROVCDDP and its parent cell line IGROV­1 were investigated. Differentially expressed EMT­-related genes identified by microarray in IGROVCDDP (IGF1R and ZEB1) were investigated by Western blotting and siRNA knockdown. EMT­-related genes were also investigated in publicly available ovarian cancer datasets.
Results: IGROVCDDP cells have decreased expression of E­-Cadherin, increased expression of N-Cadherin and vimentin and have changes in morphology and invasion consistent with EMT.
IGROVCDDP cells have decreased expression of IGF1R and increased expression of ZEB1. Knockdown of IGF1R in IGROV­1 does not lead to cisplatin resistance. Knockdown of ZEB1 in IGROVCDDP also does not lead to cisplatin sensitivity. High ZEB1 expression (HR = 1.29, n = 1928, p=5.41e­05) is a marker of poor overall survival in ovarian cancer patients. In contrast, ZEB1 is not predictive of overall survival in ovarian cancer patients treated with platinum chemotherapy.
Conclusion: The gene alterations of ZEB1 and IGF1R in IGROVCDDP appear to be independent of the platinum­-resistance phenotype. ZEB1 has the potential to be used as biomarker of prognosis in ovarian cancer patients but not of platinum chemoresistance.

Actions (login required)

View Item

Statistics

DownloadsShow export options

Export as CSVXMLJSON

Activity Overview

6 month trend

5Downloads

6 month trend

28Hits

Additional statistics are available via IRStats2.