HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

OPEN ACCESS ARTICLE

This Article Free via Open Access: OA OA Full Text Full Text (PDF) OA All Versions of this Article: 2006-0452v1 25/2/380    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dunlop, E. A. Articles by Lappin, T. R.J. Search for Related Content PubMed PubMed Citation Articles by Dunlop, E. A. Articles by Lappin, T. R.J.

CANCER STEM CELLS

Impaired Downregulation Following Erythropoietin Receptor Activation in Non-Small Cell Lung Carcinoma

^aHaematology Research Group, Centre for Cancer Research and Cell Biology, and
^bNephrology Research Group, Queen's University, Belfast, United Kingdom

Key Words. Erythropoietin • Receptor • Lung carcinoma • Downregulation

Correspondence: Elaine A. Dunlop, Ph.D., Haematology Research Laboratory, University Floor, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, United Kingdom. Telephone: 44-2890-263718; Fax: 44-2890-263927; e-mail: e.dunlop{at}qub.ac.uk

Received on July 20, 2006; accepted for publication on October 6, 2006.

First published online in STEM CELLS EXPRESS  October 12, 2006.


Recent evidence confirms the presence of erythropoietin receptors on a variety of cancer cells. This has raised concerns about the use of erythropoiesis-stimulating agents in the treatment of cancer-related anemia. Having previously identified expression of functional erythropoietin receptors in a non-small cell lung carcinoma cell line, H838, which activated key signaling pathways in response to erythropoietin stimulation, we now demonstrate impaired downregulation of the erythropoietin receptor in these tumor cells. The erythropoietin receptor is not ubiquitinated following erythropoietin stimulation in this cancer cell line, and there is no turnover of the receptor in either unstimulated or stimulated cells. Compounding this blunted response is impaired SOCS3 induction downstream of erythropoietin stimulation and an extremely delayed SOCS1 response. If this finding in non-small cell lung carcinoma is a widespread phenomenon, then impaired erythropoietin receptor downregulation and degradation in tumor cells has clinical implications for those patients receiving erythropoiesis-stimulating agents for cancer-related anemia.

This article has been cited by other articles:

				J. H. Lin, E. J. Kim, A. Bansal, J. Seykora, S. K. Richardson, X.-Y. Cha, S. Zafar, S. Nasta, M. Wysocka, B. Benoit, et al. Clinical and in vitro resistance to bexarotene in adult T-cell leukemia: loss of RXR-{alpha} receptor Blood, September 15, 2008; 112(6): 2484 - 2488. [Abstract] [Full Text] [PDF]

				M. O. Arcasoy Erythropoiesis-Stimulating Agent Use in Cancer: Preclinical and Clinical Perspectives Clin. Cancer Res., August 1, 2008; 14(15): 4685 - 4690. [Abstract] [Full Text] [PDF]

				C. A. Blau Erythropoietin in Cancer: Presumption of Innocence? Stem Cells, August 1, 2007; 25(8): 2094 - 2097. [Abstract] [Full Text] [PDF]

				T. R. J. Lappin, A. P. Maxwell, and P. G. Johnston In Reply Oncologist, August 1, 2007; 12(8): 1032 - 1034. [Full Text] [PDF]

				T. R. Lappin, A. P. Maxwell, and P. G. Johnston Warning Flags for Erythropoiesis-Stimulating Agents and Cancer-Associated Anemia Oncologist, April 1, 2007; 12(4): 362 - 365. [Full Text] [PDF]