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dc.contributor.authorMcCarthy, Brian A.
dc.contributor.authorYang, Liqun
dc.contributor.authorDing, Jane
dc.contributor.authorRen, MingQiang
dc.contributor.authorKing, William
dc.contributor.authorElSalanty, Mohammed
dc.contributor.authorZakhary, Ibrahim
dc.contributor.authorSharawy, Mohamed
dc.contributor.authorCui, Hongjuan
dc.contributor.authorDing, Han-Fei
dc.date.accessioned2012-10-26T16:40:53Z
dc.date.available2012-10-26T16:40:53Z
dc.date.issued2012-05-29en_US
dc.identifier.citationBMC Cancer. 2012 May 29; 12:203en_US
dc.identifier.issn1471-2407en_US
dc.identifier.pmid22642622en_US
dc.identifier.doi10.1186/1471-2407-12-203en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/723
dc.description.abstractBackground: Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines.
dc.description.abstractMethods: We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines.
dc.description.abstractResults: Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells.
dc.description.abstractConclusions: These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.
dc.rightsCopyright ©2012 McCarthy et al.; licensee BioMed Central Ltd.en_US
dc.subjectResearch Articleen_US
dc.titleNF-kB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumorsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3407530en_US
dc.contributor.corporatenameGHSU Cancer Center
dc.contributor.corporatenameDepartment of Pathology
dc.contributor.corporatenameDepartment of Oral Biology
refterms.dateFOA2019-04-10T00:40:26Z
html.description.abstractBackground: Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines.
html.description.abstractMethods: We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines.
html.description.abstractResults: Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells.
html.description.abstractConclusions: These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.


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