Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression.

摘要: Many tumor cells produce vascular endothelial growth factor (VEGF), which is thought to be a pivotal mediator of neoangiogenesis. Expression the VEGF gene can induced by promoting phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), activate protein kinase C (PKC). Here we show that in transient transfection assays mutated form murine p53 suppressor (ala135-->val) induces expression mRNA and potentiates TPA stimulated expression. In NIH 3T3 stably overexpress temperature sensitive (ala135-->val), displaying mutant phenotype at 37 degrees wildtype 32.5 C, induction activated PKC strongly synergistic with mutant, but not p53. Mutant specifically increases without affecting other inducible genes. dependent also enhanced human amino acid 175. Thus, our data link p53, most frequently altered tumors, regulation angiogenesis.