Erythropoietin promotes MCF-7 breast cancer cell migration by an ERK/mitogen-activated protein kinase-dependent pathway and is primarily responsible for the increase in migration observed in hypoxia.

Abstract	Recent studies indicate that cancer cells express erythropoietin receptor (EpoR). In this study, we have shown that erythropoietin (Epo) activates the mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), and promotes migration in MCF-7 breast cancer cells. Epo-stimulated MCF-7 cell migration was blocked by the MEK inhibitor PD098059 and by dominant negative MEK-1, indicating an essential role for ERK. When MCF-7 cells were exposed to hypoxia (1.0% O(2)) for 3 h, the Epo mRNA level increased 2.4 +/- 0.5-fold, the basal level of ERK activation increased, and cell migration increased 2.0 +/- 0.1-fold. Soluble EpoR and Epo-neutralizing antibody significantly inhibited hypoxia-induced MCF-7 cell migration, suggesting a major role for autocrine EpoR cell signaling. MCF-7 cell migration under hypoxic conditions was also inhibited by PD098059. These experiments identify a novel pathway by which exogenously administered Epo, and Epo that is produced locally by cancer cells under hypoxic conditions, may stimulate cancer cell migration.
Authors	Robin D Lester, Minji Jo, W Marie Campana, Steven L Gonias
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 280 Issue 47 Pg. 39273-7 (Nov 25 2005) ISSN: 0021-9258 [Print] United States
PMID	16207704 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Flavonoids Protein Kinase Inhibitors RNA, Messenger RNA, Neoplasm Receptors, Erythropoietin Recombinant Proteins Erythropoietin 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Topics	Breast Neoplasms (pathology, physiopathology) Cell Hypoxia (physiology) Cell Line, Tumor Cell Movement (drug effects, physiology) Erythropoietin (antagonists & inhibitors, genetics, metabolism, pharmacology) Female Flavonoids (pharmacology) Humans MAP Kinase Signaling System (drug effects) Neutralization Tests Protein Kinase Inhibitors (pharmacology) RNA, Messenger (genetics, metabolism) RNA, Neoplasm (genetics, metabolism) Receptors, Erythropoietin (metabolism) Recombinant Proteins

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