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- W2094192074 abstract "p53 alterations in human tumors often involve missense mutations that may confer dominant-negative or gain-of-function properties. Dominant-negative effects result in inactivation of wild-type p53 protein in heterozygous mutant cells and as such in a p53 null phenotype. Gain-of-function effects can directly promote tumor development or metastasis through antiapoptotic mechanisms or transcriptional activation of (onco)genes. Here, we show, using conditional mouse technology, that epithelium-specific heterozygous expression of mutant p53 (i.e., the p53.R270H mutation that is equivalent to the human hotspot R273H) results in an increased incidence of spontaneous and UVB-induced skin tumors. Expression of p53.R270H exerted dominant-negative effects on latency, multiplicity, and progression status of UVB-induced but not spontaneous tumors. Surprisingly, gain-of-function properties of p53.R270H were not detected in skin epithelium. Apparently, dominant-negative and gain-of-function effects of mutant p53 are highly tissue specific and become most manifest upon stabilization of p53 after DNA damage." @default.
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- W2094192074 date "2007-05-15" @default.
- W2094192074 modified "2023-10-04" @default.
- W2094192074 title "Dominant-Negative but not Gain-of-Function Effects of a <i>p53.R270H</i> Mutation in Mouse Epithelium Tissue after DNA Damage" @default.
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- W2094192074 doi "https://doi.org/10.1158/0008-5472.can-06-4681" @default.
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