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Title: Potential clinical applications of antibodies against the minichromosome maintenance (MCM) proteins
Author: Freeman, Arya Alexander
ISNI:       0000 0001 3483 7739
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2001
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The minichromosome maintenance (MCM) proteins are a family of closely related proteins with striking sequence homology. First identified in Saccharomyces cerevisiae, MCM proteins have also been characterised in Xenopm and human cells, and form part of the pre-replication complex (PRC) essential for eukaryotic DNA replication. Assembly of the PRC "licenses" progression of the cell from G1 to S phase of the cell cycle, whilst its dissociation in S phase limits the replication of DNA to once per cycle. Recent cell line studies describing the presence of MCM proteins throughout the cell cycle, and their rapid down-regulation in differentiating and quiescent cells, have suggested the use of antibodies against MCM proteins as sensitive and specific markers of proliferating cells. In this thesis, the potential utility of antibodies against the MCM proteins for the identification and accurate discrimination of dysplastic cells from reactive cell populations has been investigated in a range of histological and cytological specimens. The expression of MCM proteins was initially characterised in a range of tissues from different anatomical locations. The finding that MCM proteins are expressed in up to 90% of cells from dysplastic and neoplastic lesions, but restricted to the basal compartment of normal stratified epithelia, suggests that dysplastic cells remain in cycle due to deregulation of normal controls over cell proliferation. Using this principle, antibodies against MCM proteins have been shown to facilitate the identification of dysplastic and neoplastic cells in cytological preparations from the lung, colon and bladder and to aid their distinction from cells showing reactive or degenerative changes. Potential applications have also been identified in the differential diagnosis of inflammatory and malignant lesions with similar morphological appearances. Furthermore, MCM expression has been shown to provide useful prognostic information about the likely biological behaviour of neoplasms with indeterminate morphological features, including meningiomas and testicular Leydig cell tumours.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Neoplasms; Tumours