Influences of the p53 Status on Hypoxia-induced Gene Expression

摘要: The p53 tumor-suppressor gene is one of the most frequently mutated genes in human cancers, and its genetic alterations may play critical roles oncogenesis, tumor progression, angiogenesis. To clarify influence status on hypoxia-inducible expression, we first performed transfection assays with a hypoxia-responsive vector carrying 5 elements upstream CMV minimal promoter driving transcription luciferase various cell lines wild-type (wt) or mutant (mut) p53. As result, hypoxia responsiveness considerably varied between lines, could not obtain clear evidence that factor-1 (HIF-1) mediated expression wt-p53 cells was lower than mut-p53. It interesting SaOS2 (p53 null) showed highest activities under both aerobic hypoxic conditions among tested cells. Next, to elucidate effects endogenous wt- mut-p53s, assay Northern blot analysis for VEGF were by using isogenic variants HT1080 differing their status. mRNA apparently variant mutations alleles parental line harboring wt-p53, implying some types constitutively accumulated can decrease basal hypoxia-induced expressions addition wt-p53.