Abstract
The p53 tumour-suppressor gene is mutated in 60% of human tumours, and the product of the gene acts as a suppressor of cell division. It is thought that the growth-suppressive effects of p53 are mediated through the transcriptional transactivation activity of the protein. Overexpression of the p53 protein results either in arrest in the G1 phase of the cell cycle or in the induction of apoptosis. Both the level of the protein and its transcriptional transactivation activity increase following treatment of cells with agents that damage DNA, and it is thought that p53 acts to protect cells against the accumulation of mutations and subsequent conversion to a cancerous state. The induction of p53 levels in cells exposed to gamma-irradiation results in cell cycle arrest in some cells (fibroblasts) and apoptosis in others (thymocytes). Cells lacking p53 have lost this cell cycle control and presumably accumulate damage-induced mutations that result in tumorigenesis. Thus, the role of p53 in suppressing tumorigenesis may be to rescue the cell or organism from the mutagenic effects of DNA damage. Loss of p53 function accelerates the process of tumorigenesis and alters the response of cells to agents that damage DNA, indicating that successful strategies for radiation therapy may well need to take into account the tissue of origin and the status of p53 in the tumour.
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 Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Levine, A., Perry, M., Chang, A. et al. The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer 69, 409–416 (1994). https://doi.org/10.1038/bjc.1994.76
Issue Date:
DOI: https://doi.org/10.1038/bjc.1994.76
This article is cited by
-
Expression of p53 is significantly associated with recurrence-free survival and overall survival in pleuropulmonary blastoma (PPB): a report from the International Pleuropulmonary Blastoma/DICER1 Registry
Modern Pathology (2021)
-
Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67
International Orthopaedics (2016)
-
Expression of vimentin and survivin in clear cell renal cell carcinoma and correlation with p53
Clinical and Translational Oncology (2015)
-
Liposarcoma: a soft tissue tumor with many presentations
MUSCULOSKELETAL SURGERY (2014)
-
Analysis of P53 mutation and invasion front grading in oral squamous cell carcinomas
Journal of Huazhong University of Science and Technology [Medical Sciences] (2010)