Open AccessImpaired Downregulation Following Erythropoietin Receptor Activation in Non‐Small Cell Lung Carcinoma
Author(s) -
Dunlop Elaine A.,
Maxwell Alexander P.,
Lappin Terence R.J.
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2006-0452
Subject(s) - biology , downregulation and upregulation , erythropoietin , cancer research , receptor , lung , socs2 , small cell lung carcinoma , carcinoma , erythropoietin receptor , lung cancer , microbiology and biotechnology , medicine , endocrinology , small cell carcinoma , cancer , genetics , gene , suppressor
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.