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

Zhongqiu Zhang, Yian Wang, Ruisheng Yao, Ronald A. Lubet, Ming You

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

In this study, we did a bioassay employing mice with a dominant-negative p53 mutation (p53Val135/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 (p53WT/WT). The most striking difference between p53Val135/WT and p53WT/WT mice following the carcinogen treatment was the higher prevalence and more rapid development of SSC in p53Val135/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 p53Val135/WT and p53WT/WT mice. Microarray and GenMAPP analysis revealed that dominant-negative p53 (135Valp53) 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 p53Val135/WT mice as well as to the more rapid growth and progression of tumors.

Original languageEnglish (US)
Pages (from-to)401-410
Number of pages10
JournalMolecular Cancer Research
Volume4
Issue number6
DOIs
StatePublished - Jun 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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