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[俄罗斯鼻咽癌未分化癌患者中爱泼斯坦-巴尔病毒LMP-1基因的结构和功能特征]

[Structural and functional features of Epstein-Barr virus LMP-1 gene in patients with anaplastic carcinoma of the nasopharynx in Russia].

作者信息

Gurtsevich V E, Shcherbak L N, Novikova E V, Hahn P, Belousova N V, Arkhipov V V, Grasser F A, Müller-Lantzsch N, Pavlish O A

出版信息

Vestn Ross Akad Med Nauk. 2002(1):53-9.

Abstract

Epstein-Barr virus (EBV) is known to be closely associated with the development of anaplastic nasopharyngeal carcinoma (NPC) in some malignancy endemic regions in South-East Asia. LMP1 gene is one of the EBV latent genes, which encodes a latent membrane protein. LMP1 gene is thought to be a classical oncogene since it morphologically transforms cells in vitro and induces tumors in experimental animals in vivo. LMP1 is one of a few genes which is expressed in NPC tissues. It was first shown that C-terminus of LMP1 gene obtained from NPC patients in South-East Asia contained a deletion of 30 base pairs (bp). However, this deleted LMP1 gene was then found in the EBV isolates persisting among healthy virus carriers and patients with other EBV-associated abnormalities from both NPC endemic and non-endemic regions. The aim of this investigation was to accomplish a molecular biological analysis of EBV LMP1 genes obtained from Russian NPC patients. To this end, the authors isolated and sequenced the LMP1 clones amplified from the tumor tissues from 7 NPC patients at the N. N. Blokhin Russian Cancer Research Center and primary blood lymphocytes (PBL) from 6 healthy donors. As a result, the authors could not find the deletion of the above-mentioned 30 bp in NPC LMP1 clones, but could in one healthy donor (PBL-2). A functional analysis revealed no significant differences between LMP1 variants with or without 30 bp deletion in their capacity to activate NF kappa B and jun/AP-1 transcription factors. Nevertheless, Russian NPC-derived LMP1 variants as compared with those from PBLs featured some specific amino acid exchanges. These data indicate that the 30 bp deletion of LMP1 gene is not a factor that predisposes to NPC in Russia.

摘要

已知爱泼斯坦-巴尔病毒(EBV)与东南亚一些恶性肿瘤流行地区的未分化鼻咽癌(NPC)的发生密切相关。LMP1基因是EBV的潜伏基因之一,它编码一种潜伏膜蛋白。LMP1基因被认为是一种经典的癌基因,因为它在体外能使细胞发生形态转化,并在体内实验动物中诱发肿瘤。LMP1是在NPC组织中表达的少数基因之一。首次发现从东南亚NPC患者获得的LMP1基因的C末端缺失30个碱基对(bp)。然而,随后在NPC流行地区和非流行地区的健康病毒携带者以及患有其他EBV相关异常的患者中持续存在的EBV分离株中发现了这种缺失的LMP1基因。本研究的目的是对从俄罗斯NPC患者获得的EBV LMP1基因进行分子生物学分析。为此,作者从俄罗斯国立肿瘤研究中心的7例NPC患者的肿瘤组织和6名健康供体的外周血淋巴细胞(PBL)中分离并测序了扩增的LMP1克隆。结果,作者在NPC的LMP1克隆中未发现上述30 bp的缺失,但在一名健康供体(PBL-2)中发现了。功能分析显示,有无30 bp缺失的LMP1变体在激活NF-κB和jun/AP-1转录因子的能力上没有显著差异。然而,与来自PBL的LMP1变体相比,俄罗斯NPC来源的LMP1变体具有一些特定的氨基酸交换。这些数据表明,LMP1基因的30 bp缺失不是俄罗斯NPC发病的易感因素。

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