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[Cancer Research 60, 4010-4015, August 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Hypoxia-inducible Factor-1{alpha} Is a Positive Factor in Solid Tumor Growth

Heather E. Ryan, Michelle Poloni, Wayne McNulty, David Elson, Max Gassmann, Jeffery M. Arbeit and Randall S. Johnson1

Department of Biology, University of California, San Diego, California 92093 [H. E. R., M. P., W. M., R. S. J.]; Cancer Genetics Program, University of California, San Francisco Comprehensive Cancer Center, San Francisco, California 94143 [D. E., J. M. A.]; and Institute of Physiology, University of Zurich-Irchel, CH-8057 Zurich, Switzerland [M. G.]

Deficiencies in oxygenation are widespread in solid tumors. The transcription factor hypoxia-inducible factor (HIF)-1{alpha} 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-1{alpha}, one from embryos genetically null for HIF-1{alpha}, and the other from embryos carrying loxP-flanked alleles of the gene, which allows for cre-mediated excision. The loss of HIF-1{alpha} 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-1{alpha}-null tumors. The evidence from these experiments indicates that hypoxic response via HIF-1{alpha} is an important positive factor in solid tumor growth and that HIF-1{alpha} affects tumor expansion in ways unrelated to its regulation of VEGF expression.




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