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Am J Physiol Regul Integr Comp Physiol 286: R608-R623, 2004; doi:10.1152/ajpregu.00538.2003
0363-6119/04 $5.00
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INVITED REVIEW

HIFs and tumors—causes and consequences

Gisele Höpfl, Omolara Ogunshola, and Max Gassmann

Institute of Veterinary Physiology, University of Zürich, CH-8057 Zürich, Switzerland

For most organisms oxygen is essential for life. When oxygen levels drop below those required to maintain the minimum physiological oxygen requirement of an organism or tissue it is termed hypoxia. To counteract possible deleterious effects of such a state, an immediate molecular response is initiated causing adaptation responses aimed at cell survival. This response is mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimer consisting of an {alpha}- and a {beta}-subunit. HIF-1{alpha} protein is stabilized under hypoxic conditions and therefore confers selectivity to this response. Hypoxia is characteristic of tumors, mainly because of impaired blood supply resulting from abnormal growth. Over the past few years enormous progress has been made in the attempt to understand how the activation of the physiological response to hypoxia influences neoplastic growth. In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.

hypoxia; cancer; oxygen-sensing; oncogenes; vasculature



Address for reprint requests and other correspondence: M. Gassmann, Institute of Veterinary Physiology, Univ. of Zürich, Winterthurerstrasse 260, CH-8057 Zürich, Switzerland (E-mail: maxg{at}access.unizh.ch).




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