One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive\r\nhematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma\r\n(RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial\r\nand sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream\r\nmolecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression\r\nof solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays\r\na critical role in the development and progression of tumours in general, it is of special significance in the case of\r\nRCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers,\r\nincluding RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because\r\nthe rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in\r\nRCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current\r\nknowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are\r\nequivocal and insufficient to draw a definitive conclusion.
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