%0 Journal Article
%T Hypoxia and oxidative stress in breast cancer: Hypoxia signalling pathways
%A Christopher W Pugh
%A Jonathan Gleadle
%A Patrick H Maxwell
%J Breast Cancer Research
%D 2001
%I BioMed Central
%R 10.1186/bcr313
%X Oxygen homeostasis is of critical importance for all mammalian cells, because too much oxygen results in toxicity and too little impairs metabolism. Maintenance of oxygen levels within tight limits is essential throughout life, but is particularly important during periods of rapid cellular proliferation, both in normal development and neoplasia. Control of oxygen levels in the tissues of an animal occurs through a combination of gene regulatory, biochemical and physiological mechanisms. The present review focuses on the considerable advances that have been made during the past decade in our understanding of the gene regulatory processes involved.An important insight into the molecular basis of oxygen homeostasis arose through studies on the control of erythropoietin expression. The hormone erythropoietin is central to the feedback loop that regulates tissue oxygenation. By increasing red cell production in response to tissue hypoxia, erythropoietin increases tissue oxygen delivery, thereby mitigating the original stimulus. Interestingly, erythropoietin levels can also be increased by iron chelation. Erythropoietin levels are principally controlled by transcriptional regulation of erythropoietin gene expression by a hypoxically regulated enhancer that is located 3' to the gene. It was initially considered likely that regulation of erythropoietin gene transcription by hypoxia represents a special case. However, early studies following the identification of the erythropoietin hypoxically regulated enhancer demonstrated that it was a paradigm for a central mechanism of oxygen-regulated gene expression operative in most, if not all, cell types [1]. Subsequently, HIF was identified as the novel transcription factor that operates this enhancer; it too was found to be widely expressed and operative [2,3]. Although the activity of many transcription factors, including fos, jun and p53, is affected by tissue oxygenation, thereby influencing gene regulation, it has become incr
%K angiogenesis
%K hypoxia-inducible factor
%K oxygen
%K tumour
%K von Hippel¨CLindau
%U http://breast-cancer-research.com/content/3/5/313