Modulation of p53-induced cell cycle progression, DNA repair and apoptosis by HCV gene expression.

HCV 基因表达调节 p53 诱导的细胞周期进程、DNA 修复和细胞凋亡。

• 批准号: 08457163
• 负责人: KANEKO Yoshiyasu
• 金额: $ 2.56万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457163/
• 关键词: Hepatitis virus; p53 gene; cell cycle; DNA repair; Apoptosis; 肝炎ウィルス

The role of p53 and HCV gene expresssion on cell cycle progression, apoptosis, and DNA reapir was investigated. Anticancer drugs such as etoposide and mitomycin C induced apoptosis in human PLC/PRF/5 hepatoma cells. Nuclear accumulation of p53 was observed preceeding the apoptosis. To investigate the role of p53, we introduced p53 gene into a retroviral expression vecotr pZIP,and the retrovirus carryiing p53 gene was produced. The growth of hepatoma cells in vivo and in vivo was inhihibed by the transfer of wild-type p53 gene.An antiangiogenic compound TNP470, a derivative of Fumagillin, induced apoptosis in both hepatoma cells and vascular endothelial cells and suppressed the in vivo growth of hepatoma cells. p53 acted additively with this anti-angiogenic compound. Apoptosis of the hepatoma cells appeared to be regulated by ras-PI-3-kinase pathway and NF-kB.Both TNP470 and p53 was suggested to be playing important role in modulating these pathways and inducining apoptosis.In order to analyze the effects of HCV gene expression, the viral gene fragments were introduced into the retroviral expression vector. The analysis on the effects of expression on these genes on ras-PI-3kinase and NF-kB is known in progress.

研究了p53和HCV基因表达在细胞周期进程、细胞凋亡和DNA修复中的作用。抗癌药物足叶乙甙和丝裂霉素C诱导人肝癌PLC/PRF/5细胞凋亡。p53蛋白在细胞凋亡前有核聚集。为了研究p53基因在逆转录病毒中的作用，我们将p53基因导入逆转录病毒表达载体pZIP中，制备了携带p53基因的逆转录病毒。野生型p53基因的导入抑制了肝癌细胞在体内和体内的生长，抗血管生成化合物烟曲霉素（Fumagillin）衍生物TNP 470诱导肝癌细胞和血管内皮细胞凋亡，抑制肝癌细胞在体内的生长。p53与这种抗血管生成化合物起相加作用。肝癌细胞的凋亡受ras-PI-3-kinase通路和NF-κ B的调控，提示TNP 470和p53在调控这些通路和诱导凋亡中起重要作用。这些基因的表达对ras-PI-3激酶和NF-κ B的影响的分析正在进行中。

项目成果

T.Nakayama.: "k252a inhibits the phosphorylation of PRb without chcmging the levels of G1 cyclins and cdk2 proteins in human hepatomd cells." Biochem.Biophys.Res.Commun. 224. 180-183 (1996)

T.Nakayama.：“k252a 抑制 PRb 的磷酸化，而不改变人肝细胞中 G1 细胞周期蛋白和 cdk2 蛋白的水平。”

Y.Kaneko: "Cationic liposomes enhance retrovirua-mediated multinucleated cel formation and retroviral transduction." Cancer Lett.105. 39-44 (1996)

Y.Kaneko：“阳离子脂质体增强逆转录病毒介导的多核细胞形成和逆转录病毒转导。”

Y.Kaneko: "Structural characteristics of cationic lipasomes with potent enhancing effect on retroviral transduction into human hepatomc) cells." Cancer Lett. 107. 211-215 (1996)

Y.Kaneko：“阳离子脂质体的结构特征，对逆转录病毒转导至人肝细胞具有有效增强作用。”

T.Nakayama: "K252a inhibits the phosphorylation of pRb without changing the levels of G1 cyclins and cdk 2 proteins in human hepatomc) cells." Biochem.Biophup.Res.Commun. 224. 180-183 (1996)

T.Nakayama：“K252a 抑制 pRb 的磷酸化，而不改变人肝细胞中 G1 细胞周期蛋白和 cdk 2 蛋白的水平。”

Y.Kaneko: "Structural Characteristics of cationic liposomes with potent enhancing effect on retroviral transduction into hunan heparomd cells" Cancer Lett. 107. 211-215 (1996)

Y.Kaneko：“对逆转录病毒转导至湖南肝细胞具有有效增强作用的阳离子脂质体的结构特征”Cancer Lett。