RGD Reference Report - p53 Transgenic mice are highly susceptible to 4-nitroquinoline-1-oxide-induced oral cancer. - Rat Genome Database

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p53 Transgenic mice are highly susceptible to 4-nitroquinoline-1-oxide-induced oral cancer.

Authors: Zhang, Z  Wang, Y  Yao, R  Li, J  Lubet, RA  You, M 
Citation: Zhang Z, etal., Mol Cancer Res. 2006 Jun;4(6):401-10.
RGD ID: 8547873
Pubmed: PMID:16778087   (View Abstract at PubMed)
DOI: DOI:10.1158/1541-7786.MCR-06-0028   (Journal Full-text)

In this study, we did a bioassay employing mice with a dominant-negative p53 mutation (p53(Val135/WT)) to assess whether a germ-line p53 mutation predisposed mice toward the development of squamous cell carcinomas (SCC) in the oral cavity. Treatment of the mouse oral cavity with 4-nitroquinoline-1-oxide produced a 66%, 91%, and 20% tumor incidence in the oral cavity, esophagus, and forestomach/stomach, respectively, in p53(Val135/WT) mice. In contrast, only a 25%, 58%, and 4% tumor incidence was observed in oral cavity, esophagus, and forestomach/stomach, respectively, in wild-type littermates (p53(WT/WT)). The most striking difference between p53(Val135/WT) and p53(WT/WT) mice following the carcinogen treatment was the higher prevalence and more rapid development of SSC in p53(Val135/WT) mice than in wild-type mice. To identify the precise genes or pathways involved in these differences during tumor development, we examined gene expression profiles of 4-nitroquinoline-1-oxide-treated normal tongues as well as tongue SCC in p53(Val135/WT) and p53(WT/WT) mice. Microarray and GenMAPP analysis revealed that dominant-negative p53 ((135)Valp53) affects several cellular processes involved in SCC development. Affected processes included apoptosis and cell cycle arrest pathways, which were modulated in both tumor and normal epithelium. These results showed that reduction of p53-dependent apoptosis and increases in cell proliferation might contribute to the observed increase in oral cavity and gastroesophageal malignancies in p53(Val135/WT) mice as well as to the more rapid growth and progression of tumors.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Tp53  (tumor protein p53)

Genes (Mus musculus)
Trp53  (transformation related protein 53)

Genes (Homo sapiens)
TP53  (tumor protein p53)


Additional Information