Heat shock protein 90 inhibitors repress latent membrane protein 1 (LMP1) expression and proliferation of Epstein-Barr virus-positive natural killer cell lymphoma.

Heat shock protein 90 inhibitors repress latent membrane protein 1 (LMP1) expression and proliferation of Epstein-Barr virus-positive natural killer cell lymphoma.
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DOI:
10.1371/journal.pone.0063566
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Tsurumi T
Tsurumi T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Murata T;Iwata S;Siddiquey MN;Kanazawa T;Goshima F;Kawashima D;Kimura H;Tsurumi T

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EB病毒(EBV)LMP 1是潜伏感染中表达的主要癌蛋白。它作为TNFR家族成员发挥功能,组成性激活细胞信号,如NFκB、MAPK、JAK/STAT和AKT。我们在此筛选了小分子抑制剂和分离的HSP 90抑制剂,Radicicol和17-AAG,作为不仅在EBV阳性SNK 6自然杀伤(NK)细胞淋巴瘤细胞中,而且在B和T细胞中抑制LMP 1表达和细胞增殖的候选物。免疫缺陷NOD/Shi-scid/IL-2 R γnull(NOG)小鼠的肿瘤形成也受到抑制。这些结果表明,热休克蛋白90抑制剂可以作为EBV阳性恶性肿瘤患者的替代治疗。
Epstein-Barr virus (EBV) LMP1 is a major oncoprotein expressed in latent infection. It functions as a TNFR family member and constitutively activates cellular signals, such as NFκB, MAPK, JAK/STAT and AKT. We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells. Tumor formation in immuno-defficient NOD/Shi-scid/IL-2Rγnull (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.
DOI: 10.1002/j.1460-2075.1994.tb06900.x
发表时间: 1994-12-01
期刊: EMBO JOURNAL
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作者:
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