血管内皮生长因子
生物
转录因子
癌症研究
缺氧(环境)
缺氧诱导因子
缺氧诱导因子1
生长因子
血管生成
血管内皮生长因子A
空单元格
细胞培养
内科学
内分泌学
基因
化学
血管内皮生长因子受体
遗传学
医学
受体
有机化学
氧气
作者
Heather E. Ryan,Michelle Poloni,Wayne McNulty,David A. Elson,Max Gassmann,Jeffery M. Arbeit,Randall S. Johnson
出处
期刊:PubMed
日期:2000-08-01
卷期号:60 (15): 4010-5
被引量:280
摘要
Deficiencies in oxygenation are widespread in solid tumors. The transcription factor hypoxia-inducible factor (HIF)-1alpha 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-1alpha, one from embryos genetically null for HIF-1alpha, and the other from embryos carrying loxP-flanked alleles of the gene, which allows for cre-mediated excision. The loss of HIF-1alpha 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-1alpha-null tumors. The evidence from these experiments indicates that hypoxic response via HIF-1alpha is an important positive factor in solid tumor growth and that HIF-1alpha affects tumor expansion in ways unrelated to its regulation of VEGF expression.
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