Kustova I F, Varga E V, Eraĭzer T L, Lazarevich N L
Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478 Russia.
Genetika. 2001 Oct;37(10):1330-9.
The presented study is devoted to investigation of molecular mechanisms regulating alpha-fetoprotein (AFP) gene expression at transcriptional level. The study was carried out on AFP-positive and AFP-negative clones of rat hepatoma McA-RH 7777 that also differ in hepatocyte nuclear factors (HNF) 1 and 4 transcription levels. To examine a hypothesis of existence in AFP-non-producing clones a transcriptional factor that downregulates this gene expression, we have obtained somatic hybrids of AFP-positive and AFP-negative clones. In the obtained hybrids AFP gene expression is decreased while expression of HNF1, one of the main AFP promoter activators, is maintained. These data indicate an existence of a repressor in AFP-negative clones that determines AFP gene downregulation regardless of the HNF1 expression level.
本研究致力于在转录水平上研究调节甲胎蛋白(AFP)基因表达的分子机制。该研究在大鼠肝癌McA-RH 7777的AFP阳性和AFP阴性克隆上进行,这些克隆在肝细胞核因子(HNF)1和4转录水平上也存在差异。为了检验在不产生AFP的克隆中存在下调该基因表达的转录因子这一假设,我们获得了AFP阳性和AFP阴性克隆的体细胞杂种。在获得的杂种中,AFP基因表达降低,而AFP主要启动子激活剂之一HNF1的表达得以维持。这些数据表明在AFP阴性克隆中存在一种阻遏物,它决定了AFP基因的下调,而与HNF1的表达水平无关。