Ueba Tetsuya, Mori Hisae, Takahashi Jun A, Nozaki Kazuhiko, Hashimoto Nobuo
Department of Neurosurgery, Kishiwada City Hospital, Kishiwada, 596-8501, Osaka, and Department of Neurosurgery, Kyoto University Graduate School of Medicine, Japan.
J Neurooncol. 2006 Jun;78(2):107-11. doi: 10.1007/s11060-005-9063-3. Epub 2006 May 13.
Fibroblast growth factor-2 (FGF-2) gene expression is reported to be spatially and temporally regulated in the process of development, normal growth, and wound healing. We postulated that its constitutive expression in human malignant astrocytoma cells is due to loss of function of the regulatory mechanism of FGF-2 gene expression. Here, we report the characterization of a unique element in the FGF-2 gene promoter. We investigated the transcriptional regulation of the FGF-2 gene in a human malignant astrocytoma (U87MG) and a human hepatocellular carcinoma (HepG2) cell line. We found that a dyad symmetry element (DSE) in the FGF-2 gene promoter exhibited different promoter activities; in HepG2 cells it did, while in U87MG cells it did not, exhibit repressive activity. Examination of the relative promoter activities of the DSE in a thymidine kinase promoter revealed it exerted different activities, just as it did in the 2 cell lines studied. Gel shift assay demonstrated that 2 proteins bound to the DSE in nuclear extracts from HepG2 cells and that one protein was missing in nuclear extracts from U87MG cells. These results suggest that the DSE has a crucial role as a transcriptional regulatory element of FGF-2 gene expression.
据报道,成纤维细胞生长因子-2(FGF-2)基因表达在发育、正常生长和伤口愈合过程中受到时空调节。我们推测,其在人类恶性星形细胞瘤细胞中的组成性表达是由于FGF-2基因表达调控机制功能丧失所致。在此,我们报告了FGF-2基因启动子中一个独特元件的特征。我们研究了人类恶性星形细胞瘤(U87MG)和人类肝癌(HepG2)细胞系中FGF-2基因的转录调控。我们发现,FGF-2基因启动子中的二元对称元件(DSE)表现出不同的启动子活性;在HepG2细胞中它具有抑制活性,而在U87MG细胞中则没有。对胸苷激酶启动子中DSE的相对启动子活性进行检测发现,它表现出不同的活性,就像在我们研究的这两种细胞系中一样。凝胶迁移试验表明,有两种蛋白质与HepG2细胞核提取物中的DSE结合,而在U87MG细胞核提取物中缺少一种蛋白质。这些结果表明,DSE作为FGF-2基因表达的转录调控元件具有关键作用。