Hypoxia

All mammalian cells need oxygen. Inadequate oxygen (hypoxia) triggers cellular responses for survival and the maintenance of homeostasis. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1a protein. Despite the ubiquity and importance of hypoxia responses, very little is known about the variation in the global transcriptional response to hypoxia among different cell types and its links to tissue and cell-specific diseases. We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells (RPTECs), breast epithelial cells, smooth muscle (SMs), and endothelial cells (ECs) with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This exaggerated response was associated with a uniquely high level of HIF-1a RNA in renal cells and could be diminished by reducing HIF-1a expression via RNA interference (RNAi). A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in both breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Keywords: stimulus_or_stress_design