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Evasion of p53-mediated growth control occurs by three alternative mechanisms in transformed thyroid epithelial cells

Wyllie, F.S., Haughton, M.F., Blaydes, J.P., Schlumberger, M. and Wynford-Thomas, D. (1995) Evasion of p53-mediated growth control occurs by three alternative mechanisms in transformed thyroid epithelial cells Oncogene, 10, (1), pp. 49-59.

Record type: Article

Abstract

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.

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Published date: 5 January 1995

Identifiers

Local EPrints ID: 150591
URI: http://eprints.soton.ac.uk/id/eprint/150591
ISSN: 0950-9232
PURE UUID: c3b8b40f-2f94-4c33-856f-66deec9412be

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Date deposited: 20 Jul 2010 15:35
Last modified: 18 Jul 2017 12:57

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Contributors

Author: F.S. Wyllie
Author: M.F. Haughton
Author: J.P. Blaydes
Author: M. Schlumberger
Author: D. Wynford-Thomas

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