Opposing effects of hypoxia on expression of the angiogenic inhibitor thrombospondin 1 and the angiogenic inducer vascular endothelial growth factor.

摘要: Tumor angiogenesis, the development of new blood vessels during malignant progression, is a regulated process that has both genetic and physiological controls. Physiologically, angiogenesis stimulated by decreases in tissue oxygenation ( i.e. , hypoxia). We investigated effect hypoxia on expression two angiogenic factors reported to be genetically by the p53 tumor suppressor gene: ) the angiogenic inhibitor thrombospondin 1 (TSP-1); and b ) the angiogenic inducer vascular endothelial growth factor (VEGF). Analysis rodent cells differ their genotype (p53 +/+ or − /− indicated that vitro exposure simultaneously suppressed TSP-1 induced VEGF expression, regardless genotype. On transformation these with E1A oncogenic H- ras basal level TSP-1 was strongly diminished, whereas could still hypoxia. Consistent findings, sections of tumors derived from transformed and p53 showed protein overlapped regions hypoxia, protein below the limits detection tissue. Using panel of normal/immortalized human cells, it found the ability inhibit depends cell type and/or degree transformation. In contrast, was induced all types examined. Together, these findings suggest hypoxic oncogenic signals could interact microenvironment induce VEGF expression, promoting switch phenotype.