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Title: The insulin-like growth factor type 1 receptor and colorectal neoplasia : modelling the somatic evolution of cancers
Author: Allison, Andrew S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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This thesis examines the temporal expression of the Insulin-like growth factor type 1 receptor gene (IGF-IR) in the evolution of human colon cancer. These studies examine IGF-1R expression in human colo-rectal neoplasia by means of Northern blotting and Immunohistochemistry validated by tissue and reagent controls and by Western blotting. The studies show that in the normal human colon, adult stem cells in the basal crypt region expression high IGF-1R levels which decrease to low levels when these cells migrate to and differentiate in the mid and upper crypt regions. In the aberrant crypt focus, the transformed cells express high IGF-1R levels throughout the crypt axis despite showing varying degrees of differentiation. This pattern of high IGF-R expression occurring de novo in colo-rectal neoplasia continues with the neoplastic progression in polyps and cancers. However, reduced IGF-1R expression is seen in some advanced cancer phenotypes-in epithelial-type cancer cells that show a fully polarised morphology during epithelial-mesenchymal transformation (EMT) and in mesenchymal-type cancer cells that show a loss of cell-basement membrane or cell-cell adhesion during invasion. When these invasive cancer cells regain cell-cell adhesion, they reexpress the IGF-1R. These morphological changes account for the low levels of IGF-1R expression seen in advanced invasive cancers in the current study. These studies provide basic insights into how IGF-1R expression in normal cellular development is disrupted in tumour initiation. Additionally, the studies show how the control of IGF-1R expression might also be involved in later stage cancer progression during EMT and invasion.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available