title: Specific function of STAT3, SOCS1, and SOCS3 in the regulation of proliferation and survival of classical Hodgkin lymphoma cells.
abstract: The essential regulators in the pathogenesis of classical Hodgkin lymphoma (cHL) are still largely unknown. The malignant Hodgkin/Reed-Sternberg (HRS) cells of cHL secrete various cytokines leading to the activation of signaling pathways such as the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. In this study, we investigate the role of distinct JAK/STAT pathway components in the regulation of proliferation and survival of cHL cell lines. Electrophoretic mobility shift assay and western blot analysis revealed that the activation status of STAT family members varies in different cHL cell lines. Tyrosine kinase inhibitors of the JAK/STAT pathway blocked the activation of most of the STAT family members. This was accompanied with a strong antiproliferative effect and enhanced death of the treated cHL cell lines. Specific downregulation of STAT3 by siRNA expression decreased cell proliferation and induced apoptosis. Overexpression of SOCS1 and SOCS3 resulted in a proliferation arrest of cells with limited endogenous amount of these negative regulators, but not in cells that already express high amounts of SOCS1 and SOCS3. Our findings highlight the importance of STAT3 in cHL transformation and suggest SOCS1 and SOCS3 as potential targets for therapeutic intervention in distinct forms of cHL.
authors.affiliation: Georg-Speyer-Haus, Institute for Biomedical Research, 60596 Frankfurt, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Baus
authors.forename: Edith
authors.initials: E
authors.lastname: Pfitzner
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008954:Models, Biological; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D034741:RNA, Small Interfering; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D048031:JNK Mitogen-Activated Protein Kinases