Signaling induced by erythropoietin and stem cell factor in UT-7/Epo cells: transient versus sustained proliferation.
UT-7/Epo cells are human factor-dependent erythroleukemic cells, requiring erythropoietin (Epo) for long-term growth. Stem cell factor (SCF) stimulates proliferation of UT-7/Epo only transiently, for three to five days. An investigation of the signal transduction pathways activated by these cytokines in UT-7/Epo cells may identify those signals specifically required for sustained growth. Proliferation assays demonstrate that SCF generates a substantial growth response in UT-7/Epo cells; however, the cells do not multiply or survive past five to seven days. While Epo induces the activation of JAK2 and STAT5, SCF stimulation shows no activation of JAK2 or STATs 1, 3, or 5. The activation of MAPK (p42/44) by SCF was transient, lasting only 30 min, in contrast to Epo, which stimulated phosphorylation of p42/44 for up to 2 h. The expression of the early response genes c-fos, egr1, and cytokine-inducible SH2 protein (CIS) in response to SCF or Epo stimulation demonstrated that the transient expression of p42/44 correlated with the transient expression of c-fos and egr1. In addition, CIS was activated by Epo but not SCF. These data indicate that EpoR, JAK2, and STAT5 activation are not required for the initiation of proliferation of these erythroid cells, that the transient activation of p42/44 correlates with the transient gene expression of c-fos and egr1, and sustained expression of c-fos and egr1 as seen in UT-7/Epo cells continuously grown in Epo may be necessary for long-term proliferation.
Erickson-Miller
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CL
Department of Molecular Virology and Host Defense, SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania, USA. Connie_L_Erickson-Miller@SBPHRD.com
Pelus
L M
LM
Lord
K A
KA
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins; D053614:Janus Kinase 2; D004915:Leukemia, Erythroblastic, Acute; D008894:Milk Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019089:Stem Cell Factor / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D019089:Stem Cell Factor; D015534:Trans-Activators; D014157:Transcription Factors; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases