Transcription of human β4-galactosyltransferase 3 is regulated by differential DNA binding of Sp1/Sp3 in SH-SY5Y human neuroblastoma and A549 human lung cancer cell lines

Poor prognosis of neuroblastoma patients has been shown to be associated with increased expression of β4-galactosyltransferase (β4GalT) 3. To address the underlying mechanism of the increased expression of β4GalT3, the transcriptional regulation of the human β4GalT3 gene was investigated in SH-SY5Y human neuroblastoma cell line comparing with A549 human lung cancer cell line, in which the β4GalT3 gene expression was the lowest among four cancer cell lines examined. The core promoter region was identified between nucleotides -69 and -6 relative to the transcriptional start site, and the same region was utilized in both cell lines. The promoter region contained two Specificity protein (Sp)1/3-binding sites at nucleotide positions -39/-30 and -19/-10, and the sites were crucial for the promoter activity. Although the gene expression of Sp family transcription factors Sp1 and Sp3 was comparable in each cell line, Sp3 bound to the promoter region in SH-SY5Y cells whereas Sp1 bound to the region in A549 cells. The promoter activities were enhanced by Sp1 and Sp3 in SH-SY5Y cells. In contrast, the promoter activities were enhanced by Sp1 but reduced by Sp3 in A549 cells. Furthermore, the function of each Sp1/3-binding site differed between SH-SY5Y and A549 cells due to the differential binding of Sp1/Sp3. These findings suggest that the transcription of the β4GalT3 gene is regulated by differential DNA binding of Sp3 and Sp1 in neuroblastoma and lung cancer. The increased expression of β4GalT3 in neuroblastoma may be ascribed to the enhanced expression of Sp3, which is observed for various cancers.