Effects of hepatitis virus gene expression on the action of tumor promoters

肝炎病毒基因表达对肿瘤促进剂作用的影响

• 批准号: 04670410
• 负责人: KANEKO Yoshiyasu
• 金额: $ 1.34万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670410/
• 关键词: hepatoma; hepatitis virus; tumor promoter; apoptosis; calcium; anti-oncogene; 肝炎ウィルス; 肝癌; 癌遺伝子; B型肝炎ウイルス; C型肝炎ウイルス; 転写調節

Tumor promoter teleocidin stimulates protein kinase C of pLC/pRF/5 hepatoma cells which is structurally different from that of other kinds of cells. Teleocidin inhibits apoptosis of the hepatoma cells induced by mitomycin C and etoposide. Thapsigargin depletes endoplasmic reticulum calcium pool, and induces apoptosis of the hepatoma cells. Thapsigargin-induced apoptosis is not associated with an increased nuclear p53, while apoptosis induced by mitomycin C and etoposide is preceded by nuclear p53 accumulation. Therefore, tumor promoters may enhance carcinogenesis by modulating apoptotic processes. A possibility that hepatities viruses enhance hepatoma development by similar mechanism has been studied.

肿瘤启动子teleocidin对pLC/pRF/5肝癌细胞蛋白激酶C的激活作用与其它类型细胞的蛋白激酶C结构不同。Teleocidin抑制丝裂霉素C和依托泊苷诱导的肝癌细胞凋亡。毒胡萝卜素能耗竭内质网钙库，诱导肝癌细胞凋亡。毒胡萝卜素诱导的细胞凋亡与细胞核p53的增加无关，而丝裂霉素C和足叶乙甙诱导的细胞凋亡之前，细胞核p53的积累。因此，肿瘤促进剂可通过调节凋亡过程来增强致癌作用。肝炎病毒通过类似的机制促进肝癌发展的可能性已经被研究过。

项目成果

Tsukamoto,A.: "Thapsigorgin,an aninibitor of endoplcsmic reticulum Ca^<2+>-ATPase,enhances c-fos expression but antajonizes vacuole formation of human hepatoma cells induced by teleocidin" Biochem.Biophys.Acta. (1993)

Tsukamoto,A.：“Thhapsigorgin，一种内质网Ca^2-ATP酶的抑制剂，增强c-fos表达，但拮抗teleocidin诱导的人肝癌细胞的空泡形成”Biochem.Biophys.Acta。

Kaneko, Y., et al.: "Involvement of down regulation-resistant protein kinase C activity in teleocidin-inhibition of cell proliferation." Cancer Lett.71. 103-108 (1993)

Kaneko, Y. 等人：“下调抗性蛋白激酶 C 活性参与 teleocidin 抑制细胞增殖。”

Tsukamoto, A., et al.: "Tpapsigargin antagonizes cytokeratin assembly of human hepatoma cells induced by teleocidin." Int.Hepatol.Commun.1. 11-15 (1993)

Tsukamoto, A. 等人：“Tpapsigargin 拮抗由 teleocidin 诱导的人肝癌细胞的细胞角蛋白组装。”

Tsukamoto, A., et al.: "Thapsigargin depletes intracellular Ca^<2+> pool and induces apoptosis in human hepatoma cells." Cell Biol.Int.17. 969-970 (1993)

Tsukamoto, A. 等人：“毒胡萝卜素会消耗细胞内 Ca^2 池并诱导人肝癌细胞凋亡。”

Kaneko,Y.: "Coordinate expression of c-fos,p53 and Cytokeratin genes during mduction of hepatoma differentiatior mRNA levels measured by RT-PCR" Cancer Lett. 66. 155-164 (1992)

Kaneko,Y.：“通过 RT-PCR 测量肝癌分化 mRNA 水平的诱导过程中 c-fos、p53 和细胞角蛋白基因的协调表达”Cancer Lett。