Regulation of albumin and alpha-fetoprotein gene expression

白蛋白和甲胎蛋白基因表达的调节

• 批准号: 04670437
• 负责人: NAKATA Keisuke
• 金额: $ 0.58万
• 依托单位: Nagasaki University
• 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-04670437/
• 关键词: Alpha-fetoprotein; Albumin; Hepatoma; Hepatocyte growth factor; Colloid osmotic pressure; Butyric acid; 転写因子

Albumin and Alpha-fetoprotein (AFP) genes are tandemly arranged on human chromosome 4. However, the regulation of both genes is reciprocal after birth. In fact, AFP gene expression decreases to an almost undetectable level after birth ; in contrast, albumin gene expression remains high throughout life. The AFP gene is re-expressed in human hepatoma cells.In this study, the regulation of albumin and AFP genes by colloid osmotic pressure (COP), hepatocyte growth factor (HGF) and butyrate was analyzed using Northern blotting and CAT plasmid transfection assay. COP down-regulated both genes through the suppression of their promoter activities. HGF also repressed the AFP promoter activity, resulting in reduction of AFP mRNA level in a dose-dependent manner.Butyrate, a natural fermentation product of nomal colonic flora, inhibited cell growth in human hepatoma cells. Butyrate up-regulated the albumin gene expression, whereas it down-regulated the AFP gene expression through the modulation of their poromoter activities. Thus, it is possible that butyrate acts as a differentiation-inducer via the portal blood flow in human hepatoma cells.

白蛋白和甲胎蛋白（AFP）基因串联排列在人类4号染色体上。然而，这两种基因的调节在出生后是相互的。事实上，AFP基因表达在出生后降低到几乎检测不到的水平;相反，白蛋白基因表达在整个生命中保持高水平。AFP基因在人肝癌细胞中重新表达，本研究采用北方印迹法和CAT质粒转染法分析胶体渗透压（COP）、肝细胞生长因子（HGF）和丁酸盐对AFP基因和白蛋白基因表达的调控。COP通过抑制它们的启动子活性来下调这两个基因。丁酸盐是正常结肠植物群的天然发酵产物，能抑制人肝癌细胞的生长。丁酸通过调节促孔剂活性上调白蛋白基因表达，而下调AFP基因表达。因此，丁酸可能通过门脉血流在人肝癌细胞中起分化诱导剂的作用。

项目成果

Takuya Tsutsumi: "Regulation of albumin and alpha-fetoprotein gene expression by colloid osmotic pressure in human hepatoma cells" Gastroenterology. 104. 256-262 (1993)

Takuy​​a Tsutsumi：“人肝癌细胞中胶体渗透压对白蛋白和甲胎蛋白基因表达的调节”胃肠病学。

Takuya Tsutsumi: "Regulation of albumin and α-fetoprotein gene expression by colloid osmotic pressure in human hepatoma cells" Gastroenterology. 104. 256-262 (1993)

Takuy​​a Tsutsumi：“人肝癌细胞中胶体渗透压对白蛋白和甲胎蛋白基因表达的调节”胃肠病学。 104. 256-262 (1993)

Masahiko Hatano: "Hepatocyte growth factor down-regulates the α-fetoprotein gene expression in PLC/PRF/5 human hepatoma cells" Biochemical and Biophysical Research Communications. 189. 385-391 (1992)

Masahiko Hatano：“肝细胞生长因子下调 PLC/PRF/5 人肝癌细胞中的甲胎蛋白基因表达”《生物化学和生物物理研究通讯》189. 385-391 (1992)。

Keisuke Nakata: "A possible mechanism of inverse developmental regulation of α-fetoprotein and albumin genes" Journal of Biological Chemistry. 267. 1331-1334 (1992)

Keisuke Nakata：“甲胎蛋白和白蛋白基因逆向发育调控的可能机制”《生物化学杂志》267. 1331-1334 (1992)。

Keisuke Nakata: "Transcatheter arterial embolization of hepatic neoplasms" Critical Reviews in Oncology and Hematology. 13. 93-105 (1992)

Keisuke Nakata：“肝肿瘤的经导管动脉栓塞”肿瘤学和血液学评论。