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Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells
Erythropoietin receptor (EpoR) has been reported to be overexpressed in tumours and has raised safety concerns regarding the use of erythropoiesis-stimulating agents (ESAs) to treat anaemia in cancer patients. To investigate the potential for EpoR to be overexpressed in tumours, we have evaluated hu...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275479/ https://www.ncbi.nlm.nih.gov/pubmed/18349818 http://dx.doi.org/10.1038/sj.bjc.6604220 |
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author | Sinclair, A M Rogers, N Busse, L Archibeque, I Brown, W Kassner, P D Watson, J E V Arnold, G E Nguyen, K C Q Powers, S Elliott, S |
author_facet | Sinclair, A M Rogers, N Busse, L Archibeque, I Brown, W Kassner, P D Watson, J E V Arnold, G E Nguyen, K C Q Powers, S Elliott, S |
author_sort | Sinclair, A M |
collection | PubMed |
description | Erythropoietin receptor (EpoR) has been reported to be overexpressed in tumours and has raised safety concerns regarding the use of erythropoiesis-stimulating agents (ESAs) to treat anaemia in cancer patients. To investigate the potential for EpoR to be overexpressed in tumours, we have evaluated human tumours for amplification of the EPOR locus, levels of EPOR transcripts, and expression of surface EpoR protein. Gene amplification analysis of 1083 solid tumours found that amplification of the EPOR locus was rare with frequencies similar to other non-oncogenes. EPOR transcript levels in tumours and tumour cell lines were low in comparison with bone marrow and were equivalent to, or lower than, levels in normal tissues of tumour origin. Although EpoR mRNA was detected in some tumour lines, no EpoR could be detected on the cell surface using (125)I-Epo binding studies. This may be due to the lack of EpoR protein expression or lack of cell-surface-trafficking factors, such as Jak2. Taken together, we have found no evidence that EpoR is overexpressed in tumours or gets to the surface of tumour cells. This suggests that there is no selective advantage for tumours to overexpress EpoR and questions the functional relevance of EpoR gene transcription in tumours. |
format | Text |
id | pubmed-2275479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-22754792009-09-10 Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells Sinclair, A M Rogers, N Busse, L Archibeque, I Brown, W Kassner, P D Watson, J E V Arnold, G E Nguyen, K C Q Powers, S Elliott, S Br J Cancer Translational Therapeutics Erythropoietin receptor (EpoR) has been reported to be overexpressed in tumours and has raised safety concerns regarding the use of erythropoiesis-stimulating agents (ESAs) to treat anaemia in cancer patients. To investigate the potential for EpoR to be overexpressed in tumours, we have evaluated human tumours for amplification of the EPOR locus, levels of EPOR transcripts, and expression of surface EpoR protein. Gene amplification analysis of 1083 solid tumours found that amplification of the EPOR locus was rare with frequencies similar to other non-oncogenes. EPOR transcript levels in tumours and tumour cell lines were low in comparison with bone marrow and were equivalent to, or lower than, levels in normal tissues of tumour origin. Although EpoR mRNA was detected in some tumour lines, no EpoR could be detected on the cell surface using (125)I-Epo binding studies. This may be due to the lack of EpoR protein expression or lack of cell-surface-trafficking factors, such as Jak2. Taken together, we have found no evidence that EpoR is overexpressed in tumours or gets to the surface of tumour cells. This suggests that there is no selective advantage for tumours to overexpress EpoR and questions the functional relevance of EpoR gene transcription in tumours. Nature Publishing Group 2008-03-25 2008-03-18 /pmc/articles/PMC2275479/ /pubmed/18349818 http://dx.doi.org/10.1038/sj.bjc.6604220 Text en Copyright © 2008 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Translational Therapeutics Sinclair, A M Rogers, N Busse, L Archibeque, I Brown, W Kassner, P D Watson, J E V Arnold, G E Nguyen, K C Q Powers, S Elliott, S Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells |
title | Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells |
title_full | Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells |
title_fullStr | Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells |
title_full_unstemmed | Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells |
title_short | Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells |
title_sort | erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells |
topic | Translational Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275479/ https://www.ncbi.nlm.nih.gov/pubmed/18349818 http://dx.doi.org/10.1038/sj.bjc.6604220 |
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