Molecular mechanism of nasopharyngeal carcinoma oncogenesis by Epstein-Barr virus RNA EBERs

Epstein-Barr病毒RNA EBERs导致鼻咽癌发生的分子机制

• 批准号: 13671775
• 负责人: YOSHIZAKI Tomokazu
• 金额: $ 2.3万
• 依托单位: Kanazawa university
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671775/
• 关键词: Epstein-Barr virus; EBERs; MDCK; transformation; PKR; nasopbaryngeal carcinoma; Epstein-Barr virus; EBウイルス

EBERs is composed of EBER1 and EBER2. Transfection of EBER1+EBER2 expression vector in MDCK cell enhanced colony formation in soft agar, indicating that expression of EBERs transformed MDCK cell to potentially malignant, anchor-independent phenotype. Either EBER1 or EBER2 expression alone was not sufficient for transformation of MDCK cell to this anchor-independent character. EBERs did not protect MDCK cells from dell death in the condition of serum starvation and irradiation. EBERs are known to activates protein kinase R(PKR) which is activated by double-strand RNA. However, our in vitro kination assay revealed that EBERs did not activate PKR in MDCK cells. These results suggest that transformation of MDCK by EBERs were mediated by alternative pathway rather than PKR pathway. Expression of EBERs in nasopharyngeal carcinoma tissue tended to be correlated with advanced T stage, suggesting that EBERs promote growth and proliferation of tumor cell in nasopharyngeal carcinoma.

EBERs由EBER1和EBER2组成。EBER 1 + EBER 2表达载体转染MDCK细胞后，在软琼脂上的集落形成增加，表明EBER的表达可使MDCK细胞转化为潜在的恶性、锚点非依赖性表型。EBER 1或EBER 2单独表达不足以使MDCK细胞转化为这种锚定非依赖性特征。EBERs不能保护MDCK细胞在血清饥饿和辐射条件下的死亡。已知EBER激活蛋白激酶R（PKR），其由双链RNA激活。然而，我们的体外激酶试验表明，EBER不激活MDCK细胞中的PKR。这些结果表明EBERs对MDCK的转化是通过旁路途径而不是PKR途径介导的。鼻咽癌组织中EBERs的表达与T分期呈相关性，提示EBERs促进鼻咽癌细胞的生长和增殖。

项目成果

Murono, S., Inoue, H., Tanabe, T., Joab, I., Yoshizaki, T., Furukawa, M., Pagano, S.: "Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma c

Murono, S.、Inoue, H.、Tanabe, T.、Joab, I.、Yoshizaki, T.、Furukawa, M.、Pagano, S.：“Epstein-Barr 病毒潜伏膜蛋白 1 诱导环氧合酶 2

Maekawa K, Sato H, Furukawa M, Yoshizaki T.: "Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model."Clin Exp Metastasis. 19(6). 513-518 (2002)

Maekawa K、Sato H、Furukawa M、Yoshizaki T.：“在原位口腔鳞状细胞癌植入模型中，marimastat (BB-2516) 对颈部淋巴结转移的抑制。”Clin Exp 转移。

吉崎 智一: "上咽頭癌転移関連遺伝子発現と遺伝子治療の可能性-アスピリンは転移を抑制するか-"日本耳鼻咽喉科学会会報. 104. 791-795 (2001)

Tomokazu Yoshizaki：“鼻咽癌转移相关基因表达和基因治疗的可能性 - 阿司匹林会抑制转移吗？”日本耳鼻喉科学会通报 104. 791-795 (2001)。

Yoshizaki, T., Maruyama, Y., Sato, H., Furukawa, M.: "Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrx metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma"Int. J. Cancer. 95. 44

Yoshizaki, T.、Maruyama, Y.、Sato, H.、Furukawa, M.：“基质金属蛋白酶-2 组织抑制剂的表达与基质金属蛋白酶-2 的激活相关，并预测舌鳞状细胞癌的不良预后”Int。

Yoshizaki, T., Horikawa, T., Ren, Q., Wakisaka, N., Takeshita, H., Sheen, T. S., Lee, S. Y., Sato, H., Furukawa, M.: "Induction of interleukin-8 by Epstein-Barr virus latent membrane pretein-1 and its correlation with angiogenesis in nasopharyngeal carcin

Yoshizaki, T.、Horikawa, T.、Ren, Q.、Wakisaka, N.、Takeshita, H.、Sheen, T. S.、Lee, S. Y.、Sato, H.、Furukawa, M.：“通过诱导白细胞介素 8