Parvovirus nonstructural proteins induce an epigenetic modification through histone acetylation in host genes and revert tumor malignancy to benignancy
Parvovirus nonstructural proteins induce an epigenetic modification through histone acetylation in host genes and revert tumor malignancy to benignancy
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DOI：
10.1128/jvi.79.14.8886-8893.2005
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发表时间：
2005-07-01
影响因子：
5.4
通讯作者：
Yagami, K
中科院分区：
文献类型：
--
作者：
Iseki, H;Shimizukawa, R;Yagami, K
一些恶性肿瘤细胞在细小病毒感染后发生凋亡并恢复为良性表型。最近，我们证明了大鼠细小病毒RPV/UT也诱导大鼠胸腺淋巴瘤细胞系C58（NT）D的凋亡。然而，少数逃脱凋亡的细胞表现出与亲本细胞不同的性质，如抗凋亡，增强细胞粘附和抑制致瘤性。本研究旨在确定细小病毒诱导的表型改变（包括肿瘤抑制）的分子机制。我们证明，RPV/UT的非结构（NS）蛋白诱导C58（NT）D细胞凋亡，并抑制体内肿瘤生长。有趣的是，NS蛋白诱导睫状神经营养因子受体α的表达，其在回复突变细胞克隆中上调，并增强其基因的组蛋白乙酰化。这些结果表明，细小病毒NS通过组蛋白乙酰化调节宿主基因表达，提示可能的抑瘤机制。
Several malignant tumor cells become apoptotic and revert to the benign phenotype upon parvovirus infection. Recently, we demonstrated that the rat parvovirus RPV/UT also induces apoptosis in the rat thymic lymphoma cell line C58(NT)D. However, a minority of cells that escaped apoptosis showed properties different from the parental cells, such as resistance to apoptosis, enhanced cell adherence, and suppressed tumorigenicity. The present study was performed to determine the molecular mechanism of parvovirus-induced phenotypic modification, including oncosuppression. We demonstrated that the nonstructural (NS) proteins of RPV/UT induced apoptosis in C58(NT)D cells and suppressed tumor growth in vivo. Interestingly, NS proteins induced the expression of ciliary neurotrophic factor receptor alpha, which is up-regulated in revertant cell clones, and enhanced histone acetylation of its gene. These results indicate that parvoviral NS regulate host gene expression through histone acetylation, suggesting a possible mechanism of oncosuppression.