Quantitation of the mRNA levels of Epo and EpoR in various tissues in the ovine fetus
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Erythropoietin receptor
Mesonephros
Erythropoietin(EPO),a hematopoietic cytokine,possesses strong antiapoptotic tissue-protective properties.Recently several studies have shown that carbamylated EPO(CEPO) did not bind to the classical EPO receptor(EPOR) and did not show any hematopoietic activity.Nevertheless,CEPO showed tissue protection through its ability to bind to a new hetero-receptor complex comprising both EPOR and common β receptor(βcR) at a potency and efficacy comparable to EPO.Unlike EPO,CEPO has no effect on hematocrit.CEPO showed the antiapoptotic protective effects through its ability to limit both remodeling and the extent of the scar.
Erythropoietin receptor
Cytokine receptor
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Erythropoietin receptor
SOCS2
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Background: Expression of erythropoietin (Epo) is controlled by the transcription factor hypoxia-inducible factor-1α (HIF-1α). Epo signaling via erythropoietin receptor (EpoR) results in stimulation of cell proliferation and upregulation of the antiapoptotic protein bcl-2 followed by inhibition of apoptosis. Epo has previously been demonstrated to be associated with Schwann cell proliferation and a recent clinical case report suggested a role in vestibular schwannoma growth.
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Hypoxia
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Erythropoietin via erythropoietin receptor effectively prevents anemia, giving reasons for a clinical use of erythropoietin in patients with colorectal cancers. However, erythropoietin seems to promote survival of the neoplastic cells in hypoxic environment. The aim of this study was to evaluate immunohistochemically the expression of erythropoietin and erythropoietin receptor in 136 primary colorectal cancers with a correlation to different anatomo-clinical features. Erythropoietin correlated with erythropoietin receptor in colorectal cancers (r = 0.547, P < .00001). Erythropoietin and erythropoietin receptor expressions were statistically higher in adenocarcinomas versus mucinous carcinomas (P = .05 and P = .03, respectively) and in moderately (G2) versus poorly differentiated (G3) tumors (P = .001 and P = .02, respectively). This in vivo study is the first study that provides evidences for the presence of erythropoietin and erythropoietin receptor in human colorectal cancer. The expressions of these proteins strictly depended on grading because the better histological differentiation probably comes from trophic influence of erythropoietin and erythropoietin receptor.
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Recent studies have shown that erythropoietin (EPO) and its specific receptor (EPOR) are expressed in malignant tumors, and EPO was found to promote tumor angiogenesis and proliferation, inhibit tumor cell apoptosis,or regulate sensitivity to chemoradiothrapy. moreover,several clinical researches have also shown that EPO was not associated with improved cancer control or survival. Further,preclinical experiments will have to elucidate the multiple molecular effects of EPO on tumor progression and survival in cancer patients.
Key words:
Erythropoietin; Receptors, Erythropoietin; Neoplasms
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Over the past two decades it has emerged that, in addition to erythropoietic activity, erythropoietin (EPO) has numerous other functions, including neuro-protective, anti-apoptotic, antioxidant, angiogenetic and immunomodulatory ones. EPO interacts with two different forms of its receptor (EPOR): a homodimer receptor, responsible for the erythropoietic effects, and a heterodimer receptor, responsible for the non-erythropoietic effects. The effects on the heterodimer receptor are responsible for EPO-induced prolongation of organ transplant survival in mice and humans. The development of new molecules that selectively target the heterodimer EPOR is allowing to test the effect of long-term treatments, without the possible complications related to the increased hematocrit.
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Abstract Purpose: The use of erythropoietin in head and neck squamous cell carcinoma (HNSCC) has been associated with poor survival. This study examines the protein and mRNA expression of erythropoietin and erythropoietin receptor in HNSCC and their relation to hypoxia, hemoglobin (Hb), and clinical outcome. Experimental Design: The immunohistochemical expression of erythropoietin and erythropoietin receptor was assessed in 151 cases of HNSCC. Expression was compared with the hypoxia-dependent proteins hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase-9 (CA-9) and correlated with clinical outcome. The mRNA expression of erythropoietin and erythropoietin receptor was measured in paired samples of HNSCC. Results: Erythropoietin and erythropoietin receptor were expressed in 95% and 99% of tumors, respectively. Using a weighed expression score, there was a positive correlation between erythropoietin and erythropoietin receptor expression (r = 0.18, P = 0.03). HIF-1α (r = 0.38, P < 0.01) and CA-9 (r = 0.26, P = 0.002) correlated with erythropoietin expression, but there was no correlation with erythropoietin receptor. No correlation was found between Hb and erythropoietin (r = 0.07, P = 0.36) or erythropoietin receptor (r = −0.02, P = 0.8), and no survival difference between high and low erythropoietin or erythropoietin receptor expression (P = 0.59 and P = 0.98, respectively). The mRNA expression of erythropoietin (P = 0.03) but not erythropoietin receptor (P = 0.62) was significantly increased in 11 paired samples of HNSCC. Conclusion: In vivo, the HIF pathway regulates erythropoietin at the mRNA level but not erythropoietin receptor expression in HNSCC. Anemia does not seem to influence the hypoxic microenvironment of tumors sufficiently to alter the expression of erythropoietin. The effects of exogenous erythropoietin may be acting via receptors expressed on tumor cells in vivo, or on vascular cells, which also express the pathway.
Erythropoietin receptor
Hypoxia
SOCS2
Receptor expression
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