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Title: Transglutaminase activity : tumour growth and metastasis
Author: Knight, C. Rosamund L.
ISNI:       0000 0001 3600 9558
Awarding Body: Nottingham Polytechnic
Current Institution: Nottingham Trent University
Date of Award: 1990
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The aim of this study is to establish the importance of tissue transglutaminase activity in tumour progression and metastasis. Results from metastatic variants, grown "in vitro" and "in vivo", indicated that cytosolic transglutaminase activity was inversely related to metastatic potential. Cytosolic transglutaminase activity was also seen to decrease during the growth of highly metastatic tumours. Particulate transglutaminase activity did not vary significantly between the variants, or during tumour growth. A direct relationship between measured transglutaminase activity and the levels of ε(γ-glutamyl)lysine (a product of transglutaminase activity) was found. This validated the use of an "in vitro" activity assay for transglutaminase, and also suggested that ε(γ-glutamyl)lysine crosslinks are the product of cytosolic transglutaminase activity. Preliminary investigations into the cause of the reduction of cytosolic activity suggested an inactivation of the enzyme. Separation of antigenic transglutaminase protein by anion-exchange indicated the presence of an inactive form of transglutaminase that was clearly separable from the active particulate and cytosolic forms of the enzyme. Unlike neoplastic cells and tissues, the presence of an inactive form could not be demonstrated in control cells or normal liver. Measurement of antigen levels indicated an inverse relationship between the inactive protein and the active cytosolic enzyme, suggesting that the two forms are inter-related. From gel filtration, the molecular weight of the inactive form was found to be greater than both the particulate and cytosolic forms. Partial proteolysis of the inactive form led to its activation and to the appearance of a transglutaminase similar to the cytosolic transglutaminase. Apoptotic envelopes, formed during programmed cell death, were found to contain greater than 80% of the cellular protein crosslink ε(γ-glutamyl)lysine. indicating them to be highly crosslinked structures. A direct correlation was found between cytosolic transglutaminase activity and anootosis. suggesting a role for this enzyme in programmed cell death. A number of physical and immunological similarities between the particulate and cytosolic forms were observed. This suggests that the two forms may not be discrete enzymes, but may be modified products of the same gene.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available