دورية أكاديمية
Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells.
العنوان: | Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells. |
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المؤلفون: | Krysov, S, Dias, S, Paterson, A, Mockridge, CI, Potter, KN, Smith, K-A, Ashton-Key, M, Stevenson, FK, Packham, G |
سنة النشر: | 2012 |
المجموعة: | Queen Mary University of London: Queen Mary Research Online (QMRO) |
مصطلحات موضوعية: | Blotting, Western, Cell Cycle, Cell Membrane, Cell Proliferation, Humans, Immunoenzyme Techniques, Immunoglobulin M, Leukemia, Lymphocytic, Chronic, B-Cell, MAP Kinase Kinase 1, MAP Kinase Kinase 2, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-myc, RNA, Messenger, Real-Time Polymerase Chain Reaction, Tumor Cells, Cultured |
الوصف: | Although long considered as a disease of failed apoptosis, it is now clear that chronic lymphocytic leukemia (CLL) cells undergo extensive cell division in vivo, especially in progressive disease. Signaling via the B-cell receptor is thought to activate proliferation and survival pathways in CLL cells and also has been linked to poor outcome. Here, we have analyzed the expression of the proto-oncoprotein MYC, an essential positive regulator of the cell cycle, after stimulation of surface IgM (sIgM). MYC expression was rapidly increased after sIgM stimulation in a subset of CLL samples. The ability of sIgM stimulation to increase MYC expression was correlated with sIgM-induced intracellular calcium fluxes. MYC induction was partially dependent on the MEK/ERK signaling pathway, and MYC and phosphorylated ERK1/2 were both expressed within proliferation centers in vivo. Although stimulation of sIgD also resulted in ERK1/2 phosphorylation, responses were relatively short lived compared with sIgM and were associated with significantly reduced MYC induction, suggesting that the kinetics of ERK1/2 activation is a critical determinant of MYC induction. Our results suggest that ERK1/2-dependent induction of MYC is likely to play an important role in antigen-induced CLL cell proliferation. |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | 170 - 179 |
اللغة: | English |
العلاقة: | Blood; https://qmro.qmul.ac.uk/xmlui/handle/123456789/93591Test |
DOI: | 10.1182/blood-2011-07-370403 |
الإتاحة: | https://doi.org/10.1182/blood-2011-07-370403Test https://qmro.qmul.ac.uk/xmlui/handle/123456789/93591Test |
رقم الانضمام: | edsbas.A700D04 |
قاعدة البيانات: | BASE |
DOI: | 10.1182/blood-2011-07-370403 |
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