Activation of the Jak-Stat- and MAPK-pathways by oncostatin M is not sufficient to cause growth inhibition of human glioma cells.
We have recently described that oncostatin M (OSM), a member of the IL-6 family of cytokines, induces the differentiation of human glioma cells in culture. In order to extend this studies, we analyzed the effect of OSM on other human glioma cell lines including A172, U343-MG and T98G. All of these cell lines express the receptor components of OSM and leukemia inhibitory factor (LIF) gp130, LIFR and the OSM specific OSMRbeta. Therefore, we expected these cell lines to respond to OSM and LIF. Using specific antibodies recognizing proteins of the janus kinase (Jak-)/signal transducers and activator of transcription (Stat-) signaling cascade that has been shown to transduce the signals of the IL-6 cytokines to the nucleus, we could show that Jak1, Jak2 and Tyk2, as well as the Stat proteins Stat1, Stat3 and Stat5b were phosphorylated in all three cell lines by OSM and, at least in part, by LIF. Activation of the Stat proteins was also detected by EMSA which revealed complex formation on the Stat3 DNA-binding element and on a Stat5 binding site. Consistent with our recent findings, OSM treatment also induced the activation of the MAPK erk2 and the tyrosine phosphatase SHP-2 in cells of the A172, T98G and U343-MG cell lines. Although this activation pattern was very close to what we had observed in the GOS3 glioma cells, only T98G showed a growth inhibition in response to OSM while the A172 and the U343-MG cell lines did not respond to OSM treatment in terms of growth inhibition.
Halfter
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H
Clinic of Neurology, Westf. Wilhelms-Universität Münster, Albert-Schweitzer-Str. 33, D-48129, Münster, Germany. halfter@uni-muenster.de
Postert
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C
Friedrich
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M
Ringelstein
E B
EB
Stögbauer
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F
D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D005909:Glioblastoma; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008222:Lymphokines / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008894:Milk Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D008894:Milk Proteins; D009363:Neoplasm Proteins; C508351:OSM protein, human; D010455:Peptides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D015534:Trans-Activators; C010598:leukocyte inhibitory factor; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human; D019950:Mitogen-Activated Protein Kinase 1; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases