Student Number : 9906751K -
MSc dissertation -
School of Molecular and Cell Biology -
Faculty of Science / In addition to its crucial role in cell adhesion, β-catenin is also known to augment
gene expression by forming a complex with lymphoid enhancer factor/T-cell
factor in the nucleus. Unregulated β-catenin expression and/or its increased
nuclear presence can lead to abnormal cell proliferation, tumour invasion and
metastasis. Pertinent is the fact that the actin cytoskeleton is central to the
translocation of several nuclear proteins. This study investigated whether the actin
cytoskeleton influences the nuclear translocation of β-catenin in human
oesophageal squamous cell carcinoma (HOSCC), a metastatic disease of common
occurrence in South Africa. Disruption of the actin cytoskeleton of five
moderately differentiated HOSCC cell lines, with cytochalasin D (cytoD), showed
that the nuclear β-catenin level was unaltered in SNO, WHCO1 and WHCO5, but
decreased in WHCO3 and WHCO6. CytoD treatment did not affect the
cytoplasmic/membrane β-catenin level in these cell lines. Further examination of
the possible association between the actin cytoskeleton and nuclear β-catenin
translocation, required the design and stable transfection, of a vector containing
full-length human β-catenin cDNA into one of the HOSCC lines. Stimulation of
exogenous β-catenin expression in transfected WHCO1 cells did not increase
cellular β-catenin level, nor did the stimulation of endogenous β-catenin
expression with DMSO. In most cases (SNO, WHCO1 and WHCO5) the nuclear
distribution of β-catenin in HOSCC is independent of a functional actin
cytoskeleton, nonetheless there are some exceptions (WHCO3 and WHCO6). The
observed variation within the HOSCC lines is possibly due to specific underlying
event/s particular to the cell line. The stable level of β-catenin expression could be
a consequence of regulatory pathways in WHCO1 compensating for the induced
imbalance of β-catenin expression.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/1796 |
| Date | 16 November 2006 |
| Creators | Dahan, Yael-Leah |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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