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.

Carcinogenesis
|July 14, 2012
PubMed

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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