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Meek DW.. Tumour suppression by p53: a role for the DNA damage response? Nat Rev Cancer 9: 714-723

Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
Nature Reviews Cancer (Impact Factor: 29.54). 10/2009; 9(10):714-23. DOI: 10.1038/nrc2716
Source: PubMed

ABSTRACT Loss of p53 function occurs during the development of most, if not all, tumour types. This paves the way for genomic instability, tumour-associated changes in metabolism, insensitivity to apoptotic signals, invasiveness and motility. However, the nature of the causal link between early tumorigenic events and the induction of the p53-mediated checkpoints that constitute a barrier to tumour progression remains uncertain. This Review considers the role of the DNA damage response, which is activated during the early stages of tumour development, in mobilizing the tumour suppression function of p53. The relationship between these events and oncogene-induced p53 activation through the ARF pathway is also discussed.

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    • "Our findings and results of other studies of the role of CTAs in the regulation of proliferation and apoptoo sis in tumor cells provide the grounds for suggesting that the CTA expression in MEFs may be associated with cell response to various stress factors, as in celluu lar aging and exposure to cytostatic mitomycin C. It is known that various damaging factors (heat shock, radiation, hypoxia, and DNAAdamaging factors) actii vate p533dependent pathways that promote cell cycle arrest to start the repair or apoptosis of injured cells (Riley et al., 2008; Meek, 2009; Suvorova et al., 2012; Eichhorn et al., 2013). Cytostatic effect of protein p53 is mediated by uppregulation of expression of the proo tein regulator of the cell cycle, p21 Cip1 . "
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    • "We also further analyzed the known p53 target Eda2r, because it was the most significantly regulated gene in each of the four separate experiments, indicating the importance of this gene in the p53-mediated response in the brain. The early activation of p53 at 2 h postirradiation was first demonstrated by western blotting using an antibody against the phosphorylated form of p53 at the serine 15 residue (Fig. 4A), which is the main target of the DNA damage response to radiation (Meek, 2009). Next, we performed qRT- PCR on brains from control and 1 Gy X-irradiated p53 +/+ , p53 "
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    • "Therefore, exploring the complex formations of DNA with OPFRs is considered as an important step to provide valuable information about the genotoxicity and carcinogenicity of OPFRs. p53 is a short-lived transcription factor that has been most extensively studied in its capacity to mediate innate tumor suppression (Vousden and Lane, 2007; Meek, 2009). In animal models, loss or mutation of p53 predisposes to a range of spontaneous and induced tumors (Iwakuma and Lozano, 2007), highlighting its protective role as a barrier to tumor development. "
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