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Publication : Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging.

First Author  Hamstra DA Year  2006
Journal  Cancer Res Volume  66
Issue  15 Pages  7482-9
PubMed ID  16885345 Mgi Jnum  J:112095
Mgi Id  MGI:3655534 Doi  10.1158/0008-5472.CAN-06-1405
Citation  Hamstra DA, et al. (2006) Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging. Cancer Res 66(15):7482-9
abstractText  p53 is a key mediator of cellular response to stress, and, although its function has been carefully evaluated in vitro, noninvasive evaluation of the transcriptional activity of p53 in live animals has not been reported. To this end, we developed a transgenic mouse model wherein the firefly luciferase gene expression was dependent on the p53-responsive P2 promoter from the murine double minute 2 (MDM2) gene. Bioluminescence activity following ionizing radiation was shown to be dose, time, and p53 dependent. In addition, expression of both p53 and its activated form as well as the expression of p53 target genes (MDM2 and p21) correlated with bioluminescence activity. Temporal evaluation of p53 activity following ionizing radiation showed a distinct oscillatory pattern, which confirmed the oscillations observed previously in cultured cells. In addition, the kinetics of oscillations were altered by pretreatment with radiation-modifying agents. These results show the use of this mouse model in enhancing our understanding of the transcriptional role of p53 in vivo.
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