Hypoxia inducible factor-2α in cancer

Poorly oxygenated ( hypoxic) tumors are frequently more aggressive compared to corresponding tumors that are better oxygenated. Adaptation to hypoxia is primarily mediated by two closely related hypoxia inducible transcription factor complexes, HIF-1 and HIF-2, which become stabilized and activated at low oxygen levels. Whether HIF-1 and HIF-2 have different roles in tumorigenesis is an open question and an issue we discuss. With focus on HIF-2, we summarize reported phenotypical changes of HIF genetic models and HIF expression patterns during normal development, in adult non - malignant tissues and in tumors. We further address the much - discussed subject of target gene preferences between HIF-1 and HIF-2, given that both transcription factors bind to the same DNA motif. Finally, we also discuss the observations that the oxygen - sensitive HIF-2 alpha subunit is accumulated and active under non - hypoxic conditions as exemplified by HIF-2 alpha expressing tumor macrophages and neuroblastoma cells located in seemingly well - vascularized tumor regions and how this phenomenon is related to tumor aggressiveness.