Document Detail


Erythropoietin-induced activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK pathways promotes malignant cell behavior in a modified breast cancer cell line.
MedLine Citation:
PMID:  20353997     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Erythropoietin (Epo), the major regulator of erythropoiesis, and its cognate receptor (EpoR) are also expressed in nonerythroid tissues, including tumors. Clinical studies have highlighted the potential adverse effects of erythropoiesis-stimulating agents when used to treat cancer-related anemia. We assessed the ability of EpoR to enhance tumor growth and invasiveness following Epo stimulation. A benign noninvasive rat mammary cell line, Rama 37, was used as a model system. Cell signaling and malignant cell behavior were compared between parental Rama 37 cells, which express few or no endogenous EpoRs, and a modified cell line stably transfected with human EpoR (Rama 37-28). The incubation of Rama 37-28 cells with pharmacologic levels of Epo led to the rapid and sustained increases in phosphorylation of signal transducers and activators of transcription 5, Akt, and extracellular signal-regulated kinase. The activation of these signaling pathways significantly increased invasion, migration, adhesion, and colony formation. The Epo-induced invasion capacity of Rama 37-28 cells was reduced by the small interfering RNA-mediated knockdown of EpoR mRNA levels and by inhibitors of the phosphoinositide 3-kinase/Akt and Ras/extracellular signal-regulated kinase signaling pathways with adhesion also reduced by Janus-activated kinase 2/signal transducers and activators of transcription 5 inhibition. These data show that Epo induces phenotypic changes in the behavior of breast cancer cell lines and establishes links between individual cell signaling pathways and the potential for cancer spread.
Authors:
Zhanzhong Shi; Vivien M Hodges; Elaine A Dunlop; Melanie J Percy; Alexander P Maxwell; Mohamed El-Tanani; Terry R J Lappin
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Publication Detail:
Type:  Journal Article     Date:  2010-03-30
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  8     ISSN:  1557-3125     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-16     Completed Date:  2010-07-12     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  615-26     Citation Subset:  IM    
Copyright Information:
(c) 2010 AACR.
Affiliation:
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / genetics,  metabolism*
Carcinoma / genetics,  metabolism*
Cell Line, Tumor
Cell Movement / drug effects,  physiology
Cell Proliferation
Cell Transformation, Neoplastic / genetics,  metabolism
Enzyme Inhibitors / pharmacology
Erythropoietin / metabolism*,  pharmacology
Extracellular Signal-Regulated MAP Kinases / drug effects,  metabolism
Female
Humans
Janus Kinase 2 / drug effects,  metabolism
Neoplasm Invasiveness / genetics,  physiopathology
Phosphatidylinositol 3-Kinases / drug effects,  metabolism
Phosphorylation / physiology
Proto-Oncogene Proteins c-akt / drug effects,  metabolism
RNA Interference
Rats
Receptors, Erythropoietin / genetics
STAT5 Transcription Factor / drug effects,  metabolism
Signal Transduction / drug effects,  physiology*
Transcriptional Activation / drug effects,  physiology*
Up-Regulation / drug effects,  physiology
ras Proteins / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Receptors, Erythropoietin; 0/STAT5 Transcription Factor; 11096-26-7/Erythropoietin; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.2/JAK2 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.6.5.2/ras Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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