IL-6 induces expression of the Fli-1 proto-oncogene via STAT3.
Induction of gene expression by IL-6 has become an area of intense interest due to the role this cytokine plays in mediating aspects of inflammation, cellular differentiation, and proliferation. The ETS family of transcription factors represents a group of positive and negative regulators of transcription, that are differentially expressed in a cell and tissue specific manner. The ETS protein Fli-1 is known to induce differentiation in the erythroblastic leukemia cell line K562 along megakaryocytic developmental pathways. Here we show that IL-6 treatment of K562 induces the expression of Fli-1 via the STAT3 transcription factor. Upregulation of Fli-1 expression can be abrogated by the addition of AG490, a chemical inhibitor of JAK kinases, and by transfecting the cells with a dominant negative STAT3 expression construct.
Hodge
David R
DR
Intramural Research Support Program, NCI Cancer Research and Development Center at Frederick, Bld. 560, Rm. 31-76, Frederick, MD 21702, USA.
Li
Dapei
D
Qi
Sheng Mei
SM
Farrar
William L
WL
D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D020014:K562 Cells; D008533:Megakaryocytes / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000090063:Proto-Oncogene Mas; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015850:Interleukin-6; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one