Journal Article

Rats deficient for <i>p53</i> are susceptible to spontaneous and carcinogen-induced tumorigenesis

He-Xin Yan, Hong-Ping Wu, Charles Ashton, Chang Tong and Qi-Long Ying

in Carcinogenesis

Volume 33, issue 10, pages 2001-2005
Published in print October 2012 | ISSN: 0143-3334
Published online July 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs238
Rats deficient for p53 are susceptible to spontaneous and carcinogen-induced tumorigenesis

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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.

Journal Article.  3359 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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