B-catenin expression and associated signalling in moderately differentiated human oesophageal squamous carcinoma cell lines

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dc.contributor.author McCutcheon, Lindsay Jean Gordon
dc.date.accessioned 2009-04-01T12:37:14Z
dc.date.available 2009-04-01T12:37:14Z
dc.date.issued 2009-04-01T12:37:14Z
dc.identifier.uri http://hdl.handle.net/10539/6861
dc.description.abstract β-catenin links membrane-bound cadherins to the actin cytoskeleton, regulating cellular adhesion, and consequently metastasis. Abnormal stabilization of free, cytoplasmic β-catenin enhances its transcriptional activities. Factors affecting the adhesive and signalling roles of β-catenin may be important in metastatic diseases such as oesophageal squamous cell carcinoma (SCC). This study focuses on the expression of β-catenin in moderately-differentiated oesophageal SCCs and the impact of three signalling pathways on this. The majority of β-catenin’s expression within moderately-differentiated oesophageal SCCs, under standard in vitro conditions, was associated with the plasma membrane, rather than in the cytoplasm. This indicates that β-catenin’s role is skewed towards cell-cell adhesion, rather than its signalling activities. Lithium, a Wnt pathway mimic, elevated cytoplasmic β-catenin concentrations. Membrane concentrations subsequently increased, possibly through E-cadherin sequestration of excess cytoplasmic β-catenin. TGF-β1, alone or together with lithium, did not alter β- catenin expression. EGF transiently increased cytoplasmic β-catenin, but did not alter total concentration. However, together with lithium, EGF increased stabilized cytoplasmic β-catenin concentrations, whilst decreasing membraneassociated β-catenin levels. This indicates that EGF/lithium signals synergistically provoke β-catenin redistribution. This may be induced by posttranslational modification through tyrosine phosphorylation of plasma membrane-associated β- catenin as the concentration of tyrosine, but not serine, phosphorylated β-catenin was increased by these signals. Thus, although the adhesive role of β-catenin appears intact, exogenous signals by EGF and lithium can alter, through tyrosine phosphorylation, the signalling role of β-catenin whilst reducing its adhesive role and thus, may potentiate the metastatic properties of these cells. en
dc.language.iso en en
dc.title B-catenin expression and associated signalling in moderately differentiated human oesophageal squamous carcinoma cell lines en
dc.type Thesis en

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    Thesis (Ph.D.)--University of the Witwatersrand, 1972.

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