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- W2899326405 abstract "1930 HHV-8 is associated with the development of primary effusion lymphoma (PEL) and Kaposi’s sarcoma. Expression of the HHV-8 K1 gene driven by a ubiquitous promoter activates nuclear factor-κB and induces lymph node hyperplasia and lymphomas in transgenic mice. K1 inhibits Fas-mediated apoptosis in several lymphoma cell lines. We report here that, compared with nontransgenic littermates, K1 transgenic mice developed enlarged spleens and lymph nodes and had increased rates of tumor development by the age of 15 months. Histological examination of the enlarged spleens demonstrated enlarged germinal centers or destruction of normal spleen structures and areas with clonal expansion of lymphocytes. Because K1 blocks Fas-mediated apoptosis in human cells, we treated splenocytes from K1 transgenic mice and their nontransgenic littermates with agonist anti-Fas antibody (Jo2) for 24 hours. Next, we examined cell death by DAPI staining followed by microscopic morphological change. K1-positive splenocytes showed significantly lower percentages of cell death compared with K1-negative splenocytes (23 ± 0.6% vs. 50 ± 0.5%, P in vivo transfection approach to introduce Flag- or cMyc-tagged K1 into mice liver. Different strains of HHV-8 are identified by different K1 amino acid sequences. We transfected C57B6 mice with plasmids containing K1 from different strains of HHV-8. The expression of K1 in mouse liver was confirmed by Western blot and immunohistochemistry. Sixteen hours after transfection, mice were challenged with a lethal dose of anti-Fas antibody. Four hours after challenged with anti-Fas antibody, mice were sacrificed and liver tissues were formalin fixed and paraffin embedded. The immunohistochemical staining showed lower percentages of cleaved caspase 3-positive cells in K1-transfected liver tissue compared with vector transfected liver tissue (58 ± 15% vs. 87 ± 9%, P lower mouse death rates after challenge with anti-Fas antibody (P We now hypothesize that K1 contributes to cell survival, lymphoproliferation, and lymphoma and may have a role in HHV-8 related human cancers." @default.
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- W2899326405 date "2007-05-01" @default.
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- W2899326405 title "Preferential survival of mice and cells expressing human herpesvirus-8 K1" @default.
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