| Literature DB >> 19091459 |
N V Khromova1, P B Kopnin, E V Stepanova, L S Agapova, B P Kopnin.
Abstract
The function of p53 tumor suppressor is often altered in various human tumors predominantly through missense-mutations resulting in accumulation of mutant proteins. We revealed that expression of p53 proteins with amino-acid substitutions at codons 175 (R175H), 248 (R248W), and 273 (R273H), representing the hot-spots of mutations in various human tumors, increased the number of vessels in HCT116 human colon carcinoma xenografts and, as a result, accelerated their growth. Stimulation of tumor angiogenesis was connected with about 2-fold increase in intracellular level of reactive oxygen species (ROS). Antioxidant N-acetyl-l-aspartate (NAC) decreased vessels number in tumors formed by cells with inactivated p53 and inhibited their growth. Effect of ROS on angiogenesis in tumors expressing hot-spot p53 mutants was correlated with their ability to increase a content of HIF1 transcriptional factor responsible for up-regulation of VEGF-A mRNAs.Entities:
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Year: 2008 PMID： 19091459 DOI： 10.1016/j.canlet.2008.10.049
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679