Hypoxia-inducible factor-1α is a positive factor in solid tumor growth

HE Ryan, M Poloni, W McNulty, D Elson, M Gassmann… - Cancer research, 2000 - AACR
HE Ryan, M Poloni, W McNulty, D Elson, M Gassmann, JM Arbeit, RS Johnson
Cancer research, 2000AACR
Deficiencies in oxygenation are widespread in solid tumors. The transcription factor hypoxia-
inducible factor (HIF)-1α is an important mediator of the hypoxic response of tumor cells and
controls the up-regulation of a number of factors important for solid tumor expansion,
including the angiogenic factor vascular endothelial growth factor (VEGF). We have isolated
two cell lines nullizygous for HIF-1α, one from embryos genetically null for HIF-1α, and the
other from embryos carrying loxP-flanked alleles of the gene, which allows for cre-mediated …
Abstract
Deficiencies in oxygenation are widespread in solid tumors. The transcription factor hypoxia-inducible factor (HIF)-1α is an important mediator of the hypoxic response of tumor cells and controls the up-regulation of a number of factors important for solid tumor expansion, including the angiogenic factor vascular endothelial growth factor (VEGF). We have isolated two cell lines nullizygous for HIF-1α, one from embryos genetically null for HIF-1α, and the other from embryos carrying loxP-flanked alleles of the gene, which allows for cre-mediated excision. The loss of HIF-1α negatively affects tumor growth in these two sets of H-ras-transformed cell lines, and this negative effect is not due to deficient vascularization. Despite differences in VEGF expression, vascular density is similar in wild-type and HIF-1α-null tumors. The evidence from these experiments indicates that hypoxic response via HIF-1α is an important positive factor in solid tumor growth and that HIF-1α affects tumor expansion in ways unrelated to its regulation of VEGF expression.
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