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), 49-59.

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Description/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.

Item Type: Article
ISSNs: 0950-9232 (print)
1476-5594 (electronic)
Related URLs:
Subjects: R Medicine > R Medicine (General)
Divisions: University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
ePrint ID: 150591
Date Deposited: 20 Jul 2010 15:35
Last Modified: 27 Mar 2014 19:10
URI: http://eprints.soton.ac.uk/id/eprint/150591

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