Date of Award
2009
Degree Type
Thesis
Degree Name
Master of Science
Program
Biochemistry
Supervisor
David Rodenhiser
Second Advisor
Alan Tuck
Third Advisor
Mellissa Mann
Abstract
Epithelial-mesenchymal transition (EMT) has been implicated in the process of
breast cancer metastasis, and ZEB2 has been implicated in EMT. Some evidence exists
suggesting that epigenetic DNA methylation modifications may be involved in EMT;
however, the specific contribution of DNA methylation to ZEB2 regulation is poorly
understood. I hypothesize that aberrant hypomethylation of the ZEB2 promoter results in
increasedexpressionofZEB2incellsthathavegonethroughEMT. Iobserveddecreased
ZEB2 promoter methylation and increased ZEB2 expression in vitro in mesenchymal-like /
breast cancer cells. Functional assays performed by treating cells with epigenetic inhibitors revealed ZEB2 demethylation that correlated with ZEB2 re-expression in a cell line sub-population. As well, a region flanking the ZEB2 gene was defined as having promoter activity, and this activity was sensitive to in vitro DNA methylation. These results support my hypothesis that DNA methylation may be involved in the regulation of ZEB2 expression.
Recommended Citation
Pilon, Jenna Marie, "EPIGENETIC REGULATION OF ZEB2 IN BREAST CANCER" (2009). Digitized Theses. 4004.
https://ir.lib.uwo.ca/digitizedtheses/4004