Molecular cancer research, 2010-04, Vol.8 (4), p.615-626
2010
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Details
- Autor(en) / Beteiligte
- Titel
- Erythropoietin-induced activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK pathways promotes malignant cell behavior in a modified breast cancer cell line
- Ist Teil von
- Molecular cancer research, 2010-04, Vol.8 (4), p.615-626
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1541-7786eISSN: 1557-3125DOI: 10.1158/1541-7786.MCR-09-0264Titel-ID: cdi_proquest_miscellaneous_733891854
- Format
- –
- Schlagworte
- Animals, Breast Neoplasms - genetics, Breast Neoplasms - metabolism, Carcinoma - genetics, Carcinoma - metabolism, Cell Line, Tumor, Cell Movement - drug effects, Cell Movement - physiology, Cell Proliferation, Cell Transformation, Neoplastic - genetics, Cell Transformation, Neoplastic - metabolism, Enzyme Inhibitors - pharmacology, Erythropoietin - metabolism, Erythropoietin - pharmacology, Extracellular Signal-Regulated MAP Kinases - drug effects, Extracellular Signal-Regulated MAP Kinases - metabolism, Female, Humans, Janus Kinase 2 - drug effects, Janus Kinase 2 - metabolism, Neoplasm Invasiveness - genetics, Neoplasm Invasiveness - physiopathology, Phosphatidylinositol 3-Kinases - drug effects, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation - physiology, Proto-Oncogene Proteins c-akt - drug effects, Proto-Oncogene Proteins c-akt - metabolism, ras Proteins - drug effects, ras Proteins - metabolism, Rats, Receptors, Erythropoietin - genetics, RNA Interference, Signal Transduction - drug effects, Signal Transduction - physiology, STAT5 Transcription Factor - drug effects, STAT5 Transcription Factor - metabolism, Transcriptional Activation - drug effects, Transcriptional Activation - physiology, Up-Regulation - drug effects, Up-Regulation - physiology