ag-490 and Hodgkin-Disease

ag-490 has been researched along with Hodgkin-Disease* in 2 studies

Other Studies

2 other study(ies) available for ag-490 and Hodgkin-Disease

ArticleYear
Constitutive activation of STAT proteins in the HDLM-2 and L540 Hodgkin lymphoma-derived cell lines supports cell survival.
    Cellular signalling, 2006, Volume: 18, Issue:4

    Survival and proliferation of Hodgkin lymphoma (HL) cells are influenced by many cytokines produced by different cell types in the lymph node microenvironment. STAT, family of transcription factors, are key mediators of cytokine signaling and their perturbation contributes to various human diseases. Electrophoretic mobility shift and phosphoprotein immunoblotting analyses were used to study STAT activation in HL cell lines. We thus observed high levels of constitutively activated STAT1, 3, 5 and 6 in HDLM-2 and L540 cells, which could be correlated with JAK kinase activation. In contrast KM-H2 cells did not display STAT activation. Preventing constitutive STAT activation by specific JAK kinases inhibitors induced apoptosis of HL cell lines and was associated with a strong decrease in the expression of the anti-apoptotic genes IAP-1, IAP-2, Bcl-xL, Bfl1 and Traf1. Silencing of JAKs by specific siRNAs also induced apoptosis of HL cells. Altogether, these results suggest that aberrant STAT activation in Hodgkin cells may promote cell survival and as a consequence facilitate oncogenic transformation.

    Topics: Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cell Survival; Electrophoretic Mobility Shift Assay; Hodgkin Disease; Humans; Immunoprecipitation; Quinazolines; RNA, Small Interfering; Signal Transduction; STAT Transcription Factors; Tumor Cells, Cultured; Tyrphostins

2006
Specific function of STAT3, SOCS1, and SOCS3 in the regulation of proliferation and survival of classical Hodgkin lymphoma cells.
    International journal of cancer, 2006, Mar-15, Volume: 118, Issue:6

    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.

    Topics: Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cell Survival; Electrophoretic Mobility Shift Assay; Enzyme Inhibitors; Hodgkin Disease; Humans; JNK Mitogen-Activated Protein Kinases; Models, Biological; Oligonucleotides; Protein Binding; RNA, Small Interfering; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Transfection; Tyrphostins

2006