Induction of Signalling in Non-Erythroid Cells by Pharmacological Levels of ErythropoietinDunlop E.A. · Percy M.J. · Boland M.P. · Maxwell A.P. · Lappin T.R.
aCentre for Cancer Research and Cell Biology, Queen’s University Belfast, bHaematology Department, and cNephrology Research Group, Belfast City Hospital, Belfast, UK
Erythropoiesis is maintained by the hormone erythropoietin (Epo) binding to its cognate receptor (EpoR) on erythroid progenitor cells. The Epo-EpoR interaction initiates a signal transduction process that regulates the survival, growth and differentiation of these cells. Originally perceived as highly lineage-restricted, Epo is now recognised to have pleiotropic effects extending beyond the maintenance of red cell mass. Functional interactions between Epo and EpoR have been demonstrated in numerous cells and tissues. EpoR expression on neoplastic cells leads to concern that recombinant human erythropoietin, used to treat anaemia in cancer patients, may augment tumour growth. Here we demonstrate that EPO, at pharmacological concentrations, can activate three major signalling cascades, viz. the Jak2/STAT5, Ras/ERK and PI3K/Akt pathways in non-small cell lung carcinoma (NSCLC) cell lines. EpoR synthesis is normally under the control of GATA-1, but NSCLC cells exhibit decreased GATA-1 levels compared to GATA-2, -3 and -6, suggesting that GATA-1 is not essential for EpoR production. The increased Epo-induced signalling was not associated with a growth advantage for the NSCLC cells.
Prof. T.R. Lappin
Department of Haematology, Centre for Cancer Research and Cell Biology
Queen’s University Belfast, U Floor, Tower Block, Belfast City Hospital
Lisburn Road, Belfast, BT9 7AB (UK)
Tel. +44 2890 263718, Fax +44 2890 263927, E-Mail email@example.com
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 0, Number of References : 29
Vol. 3, No. 1-2, Year 2006 (Cover Date: May 2006)
Journal Editor: Nitsch, R.M. (Zürich)
ISSN: 1660–2854 (print), 1660–2862 (Online)
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