Molecular biologic and pathologic analysis of Epstein-Barr virus infection related salivary lymphoepithelial carcinoma

EB病毒感染相关唾液淋巴上皮癌的分子生物学和病理学分析

• 批准号: 16406033
• 负责人: CHENG Jun
• 金额: $ 7.23万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16406033/
• 关键词: lymphoepithelial carcinoma; salivary gland; EBV; LMP1 gene; cell culture; cloning; lymphoepithelial cyst; benign lymphoepithelial lesion; リンパ上皮性癌; 中国; 遺伝子導入; 塩基配列決定; NF-kB

We have collected the total 180 cases of lymphoepithelial carcinoma (LEC) of salivary gland, which were confirmed as EBV-infected tumors by various molecular biological.A complete sequence for the LMP1 gene, one of the EBV gene and has been regarded as an oncogene, was obtained from patients' tissue samples. It was cloned into an expression vector and the constructs were transfected into 293T cells. The transfected cells showed significant elevation of NFkB activities and suppressed cell growth, which were also seen in cells transfected with vectors with different LMP1 genes such as CAO, which has been isolated from a nasopharyngeal carcinoma, and B95-8, a prototype EBV. The results indicated that the expression of LMP1 affects transcription activities in LEC cells but that the overall mutations found in the present study were not always reasons for the tumorigenesis. The promoter region of the LMP1 gene was also analyzed from 20 cases of them, and all of the cases shared common mutational events in regions that were expected to be associated with transcription factors.We tried primary cultures for salivary LECs for many times. Unfortunately, however, it was hard to establish cell lines from the cells in culture. In one of the primary cultures, we were successful in maintaining cells, which were confirmed to be their salivary duct epithelial and myoepithelial characteristics as well as EBV infected.As a background disease, lymphoepithelial cyst was studied based on clinicopathological analyses of sixty-four cases of the parotid gland. The lymphoid stroma of the cyst seemed to be resulted from granulation tissue reaction of focal sialadenitis but not induced by EBV infection.Our functional study shows a new insight for EBV roles in the pathogenesis of salivary LEC, although it is still necessary to carry out further investigations for the whole mechanisms of EBV oncogenesis.

我们收集了180例涎腺淋巴上皮癌(LEC)，从患者的组织标本中获得了EBV基因之一的LMP1基因的完整序列。将其克隆到表达载体中，并将其导入293T细胞。转染组细胞中NFkB活性显著升高，细胞生长受到抑制，不同LMP1基因载体如鼻咽癌分离株CAO和EBV原型B95-8的转染组细胞中也出现这种现象。结果表明，LMP1的表达影响LEC细胞的转录活性，但本研究中发现的全部突变并不总是肿瘤发生的原因。对其中20例LMP1基因的启动子区域进行了分析，发现所有病例都存在与转录因子相关的共同突变事件。然而，不幸的是，很难从培养中的细胞建立细胞系。在其中一种原代培养中，我们成功地维持了细胞，证实了其唾液管上皮和肌上皮的特征以及EB病毒的感染。囊内淋巴间质的形成可能是由于涎腺局灶性炎症的肉芽组织反应所致，而不是由EBV感染引起的。我们的功能研究对EBV在涎腺LEC发病机制中的作用有了新的认识，但对EBV致癌的整个机制仍需进一步的研究。

项目成果

A clinicopathologic study of parotid gland lymphoepithelial cyst

腮腺淋巴上皮囊肿的临床病理学研究

• 发表时间: 2006
• 期刊: Oral Med Pathol 11(4)
• 作者: Izumi Y;Uchida E;Sunyoto and Iijima M;Wu L
• 通讯作者: Wu L

Primary cultures of Epstein-Barr virus-related lymphoepithelial carcinoma cells of the salivary gland

唾液腺 Epstein-Barr 病毒相关淋巴上皮癌细胞的原代培养

• 发表时间: 2005
• 期刊: Korean J Oral Maxillofacial Pathol 29(2)
• 作者: Cheng J;Jen KY;Zhou X;Tian Z;Maruyama S;Li J;Saku
• 通讯作者: Saku

Epstein-Barr virus infection in lymphoepithelial carcinoma of salivary glands in Sichuan Chinese

四川省唾液腺淋巴上皮癌中 Epstein-Barr 病毒感染

• 发表时间: 2004
• 期刊: Sichuan Da Xue Xue Bao Yi Xue Ban 35(4)
• 作者: Izumi Y;Uchida K;Iijima M;Wu LY
• 通讯作者: Wu LY

Benign lymphoepithelial lesion of minor salivary gland : report of a case involving the palatal mucosa

小唾液腺良性淋巴上皮病变累及腭粘膜一例报告

• 发表时间: 2004
• 期刊: Oral Oncology Extra 40(10)
• 作者: Syafriadi M;Cheng J;Jen KY;Ida-Yonemochi H;Suzuki M;Saku T;Syafriadi M;依田 浩子;山崎 学;板垣 真奈美;Yamazaki M;Ikarashi T;依田浩子;Metwaly H
• 通讯作者: Metwaly H

Primary cultures of Epstein-Barr virus-related lymphoepithelial carcinoma cells of the salivary gland.

唾液腺 Epstein-Barr 病毒相关淋巴上皮癌细胞的原代培养物。

• 发表时间: 2005
• 期刊: Korean J Oral Maxillofacial Pathol 29(2)
• 作者: Takuo Yonezawa;Yukiyoshi Kameyama;Cheng J
• 通讯作者: Cheng J