Effects of p53 mutants derived from lung carcinomas on the p53-responsive element (p53RE) of the MDM2 gene (original) (raw)
- Experimental Oncology
- Published: 01 February 1998
- PV Zacharatos,
- E Manolis,
- JA Ikonomopoulos,
- A Damalas,
- C Lamprinopoulos,
- GZ Rassidakis,
- V Zoumpourlis,
- A Kotsinas,
- AN Rassidakis,
- TD Halazonetis &
- …
- C Kittas
British Journal of Cancer volume 77, pages 374–384 (1998)Cite this article
- 364 Accesses
- 24 Citations
- Metrics details
Abstract
The present study represents a continuation of previous works in which we observed that lung carcinomas co-expressing MDM2 protein and p53 mutants (mt p53) exhibited more aggressive behaviour. In the above studies, we suggested a 'gain of function' mechanism of mt p53 proteins based on the fact that the MDM2 gene possesses a p53-responsive element (MDM2-p53RE). In this study, to prove our hypothesis, we selected 12 cases from a series of 51 bronchogenic carcinomas. In these 12 cases, we examined the ability of the expressed mt p53 to bind the MDM2-p53RE and correlated the findings with MDM2 expression. Furthermore, we constructed four of these p53 mutants and studied their transactivation properties by co-transfecting them with a reporter plasmid carrying MDM2-p53RE in the p53 null non-small-cell lung carcinoma cell line (NSCLC) H1299. We observed mutant p53 protein DNA-binding activity, which depended on the nature and the position of the amino acid substitution. The fact that the cases with DNA-binding activity were accompanied with MDM2 protein isoforms' overexpression is indicative of a 'gain of function' phenotype. This hypothesis was enforced by the findings of the transfection experiments, which revealed that certain p53 mutants enhanced the expression of the luciferase reporter gene either directly or indirectly via a dominant positive effect on the wild-type p53. In conclusion, this work is one first attempt to examine if the deregulation of the p53/MDM2 autoregulatory feedback loop is due to novel properties of certain p53 mutants in the specific environment of a subset of bronchogenic carcinomas.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Similar content being viewed by others
Author information
Authors and Affiliations
- Department of Histology and Embryology, University of Athens, School of Medicine, Greece
VG Gorgoulis
Authors
- VG Gorgoulis
You can also search for this author inPubMed Google Scholar - PV Zacharatos
You can also search for this author inPubMed Google Scholar - E Manolis
You can also search for this author inPubMed Google Scholar - JA Ikonomopoulos
You can also search for this author inPubMed Google Scholar - A Damalas
You can also search for this author inPubMed Google Scholar - C Lamprinopoulos
You can also search for this author inPubMed Google Scholar - GZ Rassidakis
You can also search for this author inPubMed Google Scholar - V Zoumpourlis
You can also search for this author inPubMed Google Scholar - A Kotsinas
You can also search for this author inPubMed Google Scholar - AN Rassidakis
You can also search for this author inPubMed Google Scholar - TD Halazonetis
You can also search for this author inPubMed Google Scholar - C Kittas
You can also search for this author inPubMed Google Scholar
Rights and permissions
About this article
Cite this article
Gorgoulis, V., Zacharatos, P., Manolis, E. et al. Effects of p53 mutants derived from lung carcinomas on the p53-responsive element (p53RE) of the MDM2 gene.Br J Cancer 77, 374–384 (1998). https://doi.org/10.1038/bjc.1998.60
- Issue Date: 01 February 1998
- DOI: https://doi.org/10.1038/bjc.1998.60