The University of Southampton
University of Southampton Institutional Repository

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

Evasion of p53-mediated growth control occurs by three alternative mechanisms in transformed thyroid epithelial cells
Evasion of p53-mediated growth control occurs by three alternative mechanisms in transformed thyroid epithelial cells
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.
0950-9232
49-59
Wyllie, F.S.
c03ebe9e-072e-422e-8e72-7f18907a9c17
Haughton, M.F.
3ff17211-f87e-47fe-839e-9dbdaf57f66e
Blaydes, J.P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Schlumberger, M.
0426090b-5421-4ace-8f3a-1aaa6261e183
Wynford-Thomas, D.
e2abffc0-8c45-4681-b36b-6f1e0fba8ec7
Wyllie, F.S.
c03ebe9e-072e-422e-8e72-7f18907a9c17
Haughton, M.F.
3ff17211-f87e-47fe-839e-9dbdaf57f66e
Blaydes, J.P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Schlumberger, M.
0426090b-5421-4ace-8f3a-1aaa6261e183
Wynford-Thomas, D.
e2abffc0-8c45-4681-b36b-6f1e0fba8ec7

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.

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.

This record has no associated files available for download.

More information

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
ORCID for J.P. Blaydes: ORCID iD orcid.org/0000-0001-8525-0209

Catalogue record

Date deposited: 20 Jul 2010 15:35
Last modified: 23 Jul 2022 01:47

Export record

Contributors

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×