Gene expression profiling of hypoxia signaling in human hepatocellular carcinoma cells.

CELLS, TISSUES, AND ORGANISMS are said to be hypoxic when they receive less than normal levels of oxygen. Given the central role of oxygen in the production of ATP through oxidative phosphorylation, it is critical for cells and tissues to respond rapidly to hypoxia. The importance of hypoxia signaling is further highlighted by its essential role in mammalian development and several pathological conditions such as cardiovascular disease and cancer (4). The primary response to hypoxia within the cell is the upregulation of proteins and pathways such as glycolytic enzymes and angiogenic factors that ultimately lead to alternative routes of ATP generation and an increased oxygen availability (10). Glycolytic enzymes that are targets for such upregulation include glyceraldehydes-3-phosphate dehydrogenase (GAPDH), pyruvate kinase, and phophofructokinase (27). At the tissue level, there is a stimulation of angiogenesis through the upregulation of growth factors such as vascular endothelial growth factor (VEGF) (19). These responses and others are regulated by a family of transcription