Pharmacogenomics - PhD and honours Projects - Epithelial-to-mesenchymal transition in human breast cancer
Epithelial-to-mesenchymal transition in human breast cancer
Project Type
PhD
Summary
Epithelial-to-Mesenchymal Transition (EMT) is a process whereby stationary (sessile) epithelial cells, or epithelial cancer cells (carcinoma cells) dramatically alter their phenotype to adopt the mesenchymal characteristics of motility, invasiveness, and resistance to cell death (apoptosis) caused by lack of extracellular matrix (anoikis). They lose their apico-basal polarity and adopt a front-back polarity. Recent studies have shown that distant metastases closely resemble to original primary tumour, suggesting that the changes required for all these activities should be reversed, and indeed the opposite transition (mesenchymal-to-epithelial transition (MET) has been described in development and cancer. The honours student will use a series of pharmacological inhibitors to determine the signal transduction pathways which are important for the EGFR-induced EMT. Pathways known to stimulated by EGF will be targeted, and effects measured by immunocytochemistry and quantitative RT-PCR. Ultimately, the importance of a specific pathway will be tested by the introduction of dominant negative or constitutively active expression constructs.