Title of article :
p53 hot-spot mutants increase tumor vascularization via ROS-mediated activation of the HIF1/VEGF-A pathway
Author/Authors :
S.A. Khromova، نويسنده , , N.V. and Kopnin، نويسنده , , P.B. and Stepanova، نويسنده , , E.V. and Agapova، نويسنده , , L.S. and Kopnin، نويسنده , , B.P.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2009
Pages :
9
From page :
143
To page :
151
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.
Keywords :
VEGF , p53 mutation , HIF1 , ROS , Tumor angiogenesis
Journal title :
Cancer Letters
Serial Year :
2009
Journal title :
Cancer Letters
Record number :
1813522
Link To Document :
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