Journal article
Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo
TJ Phesse, KB Myant, AM Cole, RA Ridgway, H Pearson, V Muncan, GR Van Den Brink, KH Vousden, R Sears, LT Vassilev, AR Clarke, OJ Sansom
Cell Death and Differentiation | Published : 2014
DOI: 10.1038/cdd.2014.15
Abstract
Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely abrogated the immediate wave of apoptosis following both ionizing irradiation and cisplatin treatment, recapitulating the phenotype of p53 deficiency ..
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Awarded by Biotechnology and Biological Sciences Research Council
Funding Acknowledgements
This work was funded by Cancer Research UK, AICR, BBSRC and NH&MRC of Australia (#603127). We thank Dave Gillespie and Lye Mun Tho for pCHK1 antibody and protocol, Colin Nixon for Histology, and Genotyping/Biological Services.