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.
Keywords: Specificity protein 1 (Sp1); colon cancer; transcription factor; transcriptional mechanism; β4-galactosyltransferase 4.