Nakao K, Nakata K, Mitsuoka S, Ohtsuru A, Ido A, Hatano M, Sato Y, Nakayama T, Shima M, Kusumoto Y
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Biochem Biophys Res Commun. 1991 Feb 14;174(3):1294-9. doi: 10.1016/0006-291x(91)91562-q.
Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit hepatocyte growth in vitro and in vivo. In this study, we analyzed the effect of TGF-beta 1 on alpha-fetoprotein (AFP) and albumin gene expression in HuH-7 human hepatoma cells. TGF-beta 1 inhibited cell growth in a dose dependent manner. The cellular secretion rate of AFP but not albumin was suppressed significantly by TGF-beta 1. TGF-beta 1 caused a significant reduction in the level of AFP mRNA. In contrast, the levels of albumin mRNA or beta-actin mRNA were not changed by TGF-beta 1. In transient transfection experiments, TGF-beta 1 resulted in selective repression of AFP promoter activity. These results suggest that TGF-beta 1 is one of the key factors involved in the differential regulation of the AFP gene and the albumin gene.
已知转化生长因子β1(TGF-β1)在体外和体内均可抑制肝细胞生长。在本研究中,我们分析了TGF-β1对HuH-7人肝癌细胞中甲胎蛋白(AFP)和白蛋白基因表达的影响。TGF-β1以剂量依赖方式抑制细胞生长。TGF-β1显著抑制AFP的细胞分泌率,但对白蛋白无此作用。TGF-β1导致AFP mRNA水平显著降低。相比之下,TGF-β1未改变白蛋白mRNA或β-肌动蛋白mRNA的水平。在瞬时转染实验中,TGF-β1导致AFP启动子活性受到选择性抑制。这些结果表明,TGF-β1是参与AFP基因和白蛋白基因差异调节的关键因子之一。