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- _5 value "Given the multiplicity of mechanisms activating the HIF system in cancer, and the many HIF target genes involved in the angiogenic process, it is tempting to propose a simple system whereby activation of HIF in cancer promotes angiogenesis and hence tumor growth. If true, such a model would strongly support the HIF system as an anticancer target. Several studies have sought to test this model genetically in studies of experimental tumor formation by cells that are defective in particular components of the HIF pathway. The first of these used a series of mouse hepatoma cells that are functionally defective for HIF-1beta and cannot form an active HIF complex. When grown as subcutaneous tumors, the mutant cells manifest a near-total loss of the peri-necrotic enhancement of VEGF gene expression that is apparent in wild-type cells. This was associated with marked reductions in tumor angiogenesis and growth rates106. Similar reductions in growth and vascular density in tumors grown from human colon and breast carcinoma cell lines have been observed after expression of a peptide that antagonizes HIF transcription by abrogating the interaction of HIF-alpha and p300 (ref. 107)." provenance.