A potential motor neurone-specific monoclonal antibody (MN-1)
Rogers, A.T., Harrison, R., Blaydes, J., Barnes, J. and Lunt, G.G. (1991) A potential motor neurone-specific monoclonal antibody (MN-1). Biochemical Society Transactions, 19, (3), 49-59.
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Using the thyroid as a model of multistep epithelial tumorigenesis, we have used representative cell lines to correlate the degree of malignant transformation with the functional status of p53 and the integrity of cell-cycle check-points. Three distinct phenotypes were observed: Type I lines, derived from poorly-differentiated human thyroid cancers, expressed high levels of mutant p53 protein; Type II, also poorly-differentiated but derived from rat, showed over-expression of wild-type (wt) p53 with marked cell-cell heterogeneity: Type III, from well-differentiated human cancers, contained uniformly low levels of wt p53. All cell lines containing wt p53 retained a near-normal induction of p53 by DNA damage. However, the ability to undergo growth arrest differed strikingly. Whereas Type I and II lines had lost both G2/M and G1/S check points, Type III cells retained both. In Type III cells, as in diploid human fibroblasts, mutant p53 expression specifically abrogated G1/S check-point function with no other change in phenotype. These data demonstrate 3 mechanisms for evasion of p53 growth control: (i) direct mutation (ii) indirect inactivation, or (iii) 'avoidance' of activation, most probably due to failure to reach a critical threshold of DNA damage.
|Subjects:||R Medicine > R Medicine (General)|
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||20 Jul 2010 15:45|
|Last Modified:||02 Mar 2012 11:54|
|Contributors:||Rogers, A.T. (Author)
Harrison, R. (Author)
Blaydes, J. (Author)
Barnes, J. (Author)
Lunt, G.G. (Author)
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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