The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer

Abstract

Aberrant expression of the glycoprotein mucin-1 (MUC1) has been associated with pancreatic cancer progression and metastasis as a result of mediating the oncogenic transcriptional regulation of target genes. In the present study, we demonstrate that MUC1 downregulates the expression of the tumor suppressor polypeptide N-acetylgalactosaminyltransferase 5 in pancreatic cancer. ChIP-on-chip analysis revealed that the MUC1 cytoplasmic tail binds to regulatory elements in the GALNT5 gene. Additionally, MUC1 increases binding of p53 and c-Jun and decreases the binding of Sp1 to the proximal promoter and exonic regions of GALNT5. We also observed that expression of N-acetylgalactosaminyltransferase 5 is inversionally proportional to MUC1 expression in human pancreatic cancer. These results demonstrate that MUC1 downregulates the expression of N-acetylgalactosaminyltransferase 5 in pancreatic cancer by modifying the promoter occupancy of transcription factors through its cytoplasmic domain.