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Updated: May 20, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Rats deficient for p53 are susceptible to spontaneous and carcinogen-induced tumorigenesis
He-Xin Yan1, Hong-Ping Wu, Charles Ashton
1Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA 90033, USA.
Abstract:
The p53 tumor suppressor gene is highly mutated in human cancers. Individuals who inherit one p53 mutant allele are susceptible to a wide range of tumor types, including breast cancer and sarcoma. We recently generated p53 knockout rats through gene targeting in embryonic stem cells. Here we show that rats homozygous for the null allele are prone to early onset spontaneous sarcomas and lymphoma with high incidence of metastases. Heterozygous rats are also highly predisposed to cancer, but with a delayed onset and a wider spectrum of tumor types compared with homozygotes. Importantly, up to 20% of female heterozygotes developed breast cancer and about 70% of the tumors were positive for estrogen receptor. Exposing p53-deficient rats to a low dose of the carcinogen diethylnitrosamine dramatically decreased the latency for sarcoma development and survival time compared with equivalently treated wild-type rats. These unique features make this knockout line a valuable model for investigating human malignancy and in vivo carcinogenicity of chemicals and therapeutic compounds.
Insights
p53 knockout rats develop various cancers, including sarcomas and lymphomas. This new p53-deficient rat model is crucial for studying human cancer and chemical carcinogenicity.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The p53 tumor suppressor gene is frequently mutated in human cancers.
- Inherited p53 mutations predispose individuals to diverse tumor types, such as breast cancer and sarcoma.
Purpose of the Study:
- To characterize a novel p53 knockout rat model for cancer research.
- To investigate the role of p53 in spontaneous and carcinogen-induced tumorigenesis.
Main Methods:
- Generation of p53 knockout rats using gene targeting in embryonic stem cells.
- Phenotypic analysis of homozygous and heterozygous p53-deficient rats.
- Assessment of carcinogen-induced tumor development in p53-deficient and wild-type rats.
Main Results:
- Homozygous p53-deficient rats exhibited early-onset sarcomas and lymphomas with high metastatic incidence.
- Heterozygous rats showed delayed cancer onset with a broader tumor spectrum, including estrogen receptor-positive breast cancer in females.
- Diethylnitrosamine exposure accelerated sarcoma development and reduced survival in p53-deficient rats compared to wild-type.
Conclusions:
- The p53 knockout rat line serves as a valuable preclinical model for human cancers.
- This model is instrumental for studying the in vivo carcinogenicity of chemicals and therapeutic agents.
- The findings highlight the critical role of p53 in preventing spontaneous and induced tumorigenesis.
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