References
Query Results -- Details
MGI Accession ID: MGI:3711397
J Number: J:121734
Other Accession IDs:
Title: Dominant-negative but not gain-of-function effects of a p53.R270H mutation in mouse epithelium tissue after DNA damage.
Authors: Wijnhoven SW; Speksnijder EN; Liu X; Zwart E; vanOostrom CT; Beems RB; Hoogervorst EM; Schaap MM; Attardi LD; Jacks T; van Steeg H; Jonkers J; de Vries A
Journal: Cancer Res
Volume: 67
Issue: 10
Date: 2007 May 15
Year: 2007
Pages: 4648-56
Review Status: Peer Reviewed
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.
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