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Title: Protease activated receptors - investigating their role in oesophageal cancer
Author: O'Kane, William Anthony
ISNI:       0000 0001 3453 1713
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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This thesis investigates the role of a novel subset of the G-protein coupled receptor . family known as protease activated receptors (PARs) in oesophageal cancer. It pays specific attention to the relationship between the activation of these receptors and the matrix degrading enzymes of the matrix metalloproteinase family. Oesophageal adenocarcinoma has become the predominant form of oesophageal cancer in Western populations with a rapi~ rise over the last number of decades. Aetiological studies of this malignancy suggest that gastro-oesophageal reflux disease is the major risk factor. However the agent present in the refluxate which is responsible for this effect remains controversial. It is hypothesised that inappropriate activation of PAR-2 by duodenal thrombin present in the reflux mixture plays a role. The presence of functional PAR-1 and PAR-2 was determined on each of three ~esophageal cancer cell lines; two examples of squamous cell carcinoma and a third cell line initiated from an oesophageal adenocarcinoma. RT-PCR, IHC and calcium mobilisation assays were performed. RT-PCR also demonstrated the expression of PAR-3 mRNA in each of the cell lines. Proliferation assays and wound healing assays examined the effect that activation of both PAR-1 and PAR-2 had on the growth of each cell line. PAR stimulation appeared to halt the growth of the cells compared to the unstimulated control. Gelatin zymography revealed the presence of large quantities of secreted MMP-2 and lesser quantities of MMP-9 in supernatants extracted from the three cell lines. These observations were supported by the use of MMP activity assays and ELiSAs. Invasion assays also implicated MMPs in the invasion of the cell lines and also showed that PAR-2 stimulation of one of the squamous cell lines increased its invasive potential.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available