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Title: Integrin affinity modulation and lung cancer
Author: Buttery, Robert Christians
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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Recent work has shown that the transmembrane protein CD98 is able to influence the affinity with which β1 integrins bind to extracellular ligands. The first part of this thesis presents confocal microscopy and co-immunoprecipitation experiments that confirm the physical juxtaposition of the two proteins within the cell membrane, suggesting a direct functional link between the two. It also demonstrated that cross-linking CD98 stimulates both phosphoinositide 3-kinase intracellular signalling and increased β1 integrin-dependent cellular adhesion. Because of the role of CD98 in integrin affinity modulation, the immunohistochemical expression of CD98 and its ligand, galectin-3, was studied in a variety of human ling diseases including lung cancers. The major finding of this work was a striking distinction between high expression of galectin-3 in non-small cell lung cancer and low expression in small cell lung cancer. This may hag significant implications for the differing clinical behaviours of these two groups of cancers. The final section of this thesis returns to describe experiments aimed at defining the molecular regulators of integrin affinity more clearly. A genetic screen of a cDNA library was undertaken to identify candidate genes coding for proteins able to rescue integrins from the low affinity state induced by the small signalling protein H-Ras. This identified a candidate cDNA 480, recognised to be part of a novel gene Nessie, which codes for a large protein with multiple transmembrane domains. Both 480 and Nessie appear to have the ability to rescue integrin affinity from H-Ras suppression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available