HIFs and tumors--causes and consequences.
For most organisms oxygen is essential fo 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 counter act 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.
Institute of Veterinary Physiology, University of Zürich, Winterthurerstrasse 260, CH-8057 Zürich, Switzerland.
Gisele
G
Höpfl
Omolara
O
Ogunshola
Max
M
Gassmann
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009857:Oncogenes / Q000235:genetics / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D010766:Phosphorylation; D014157:Transcription Factors
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D006133:Growth Substances; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors