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Studying the Effects of p120 and Kaiso-Mediated Gene Regulation on Epithelial-to-Mesenchymal-Transition

<p> Downregulation of E-cadherin is a frequent event in epithelial cancers and it correlates
with weakened cell-cell adhesion and the induction of an epithelial-to-mesenchymal transition (EMT). It is postulated that E-cadherin downregulation liberates the catenin p120 and allows p120's translocation to the nucleus where it interacts with and functionally regulates the novel BTB/POZ transcription factor, Kaiso. Kaiso mediates transcriptional repression of various tumourigenesis-associated genes via methylated CpG dinucleotides or a sequence-specific Kaiso binding site (KBS). The Kaiso/p120 interaction has been detected in E-cadherin expressing cells of various origins, but is seldom detected in N-cadherin expressing cells or cells that have undergone EMT. We hypothesize that p120 and Kaiso play a role in EMT by modulating the expression of EMT-associated genes. We demonstrated that TGF-β-induced EMT occurs in a dose- and time-dependent manner in NMuMG cells but not in FHL-124 cells. In both cells lines, the Kaiso/p120 interaction occurred irrelevant of EMT induction by TGF-β. In NMuMG cells, the expression of p120 increased with EMT induction, while the expression of
Kaiso remained unchanged. Finally, misexpression of Kaiso and p120 in mammary
epithelial cells affected TGF-β-mediated EMT induction by delaying the upregulation of the positive mesenchymal markers, N-cadherin and α-SMA.</p> / Thesis / Master of Science (MSc)

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/21666
Date11 1900
CreatorsAlmardini, Mai
ContributorsDaniel, Juliet, Biology
Source SetsMcMaster University
Languageen_US
Detected LanguageEnglish
TypeThesis

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