Sugiyama Atena, Fukushima Naomichi, Sato Takeshi
Laboratory of Glycobiology, Department of Bioengineering, Nagaoka University of Technology.
Biol Pharm Bull. 2017 May 1;40(5):733-737. doi: 10.1248/bpb.b17-00064. Epub 2017 Feb 23.
Increased expression of β4-galactosyltransferase (β4GalT) 4 has been shown to be associated with metastatic ability and poor prognosis of colon cancer cells. To solve the up-regulation of β4GalT4 in colon cancer cells at transcriptional level, we examined the transcriptional mechanism of the β4GalT4 gene in SW480 human colon cancer cell line. Luciferase assay using the deletion constructs revealed that the promoter activity of the β4GalT4 gene is associated with the region between nucleotides -122 and -55 relative to the transcriptional start site, which contained one Specificity protein 1 (Sp1)-binding site. The mutation into the Sp1-binding site resulted in dramatic decreased promoter activity. Meanwhile, ectopic Sp1 expression stimulated the promoter activity significantly. The present study suggests that the expression of the β4GalT4 gene is controlled by Sp1, and Sp1 plays a key role in the activation of the β4GalT4 gene in colon cancer cells.
β4-半乳糖基转移酶(β4GalT)4的表达增加已被证明与结肠癌细胞的转移能力和不良预后相关。为了在转录水平解决结肠癌细胞中β4GalT4的上调问题,我们研究了SW480人结肠癌细胞系中β4GalT4基因的转录机制。使用缺失构建体的荧光素酶测定表明,β4GalT4基因的启动子活性与相对于转录起始位点的核苷酸-122至-55之间的区域相关,该区域包含一个特异性蛋白1(Sp1)结合位点。Sp1结合位点的突变导致启动子活性显著降低。同时,异位Sp1表达显著刺激了启动子活性。本研究表明,β4GalT4基因的表达受Sp1控制,并且Sp1在结肠癌细胞中β4GalT4基因的激活中起关键作用。