Gene expression of O-GlcNAc cycling enzymes in human breast cancers

Abstract

O-GlcNAcylation is an abundant, dynamic, and inducible posttranslational modification in which single β-N-acetylglucosamine residues are attached by O-glycosidic linkage to serine or treonine residues. It is suggested that abnormally regulated O-GlcNAcylation may contribute to the pathology of cancer. Cycling of O-GlcNAc residues on intracellular proteins is controlled by two enzymes, O-GlcNAc transferease (OGT), which catalyses the addition of O-GlcNAc residues and nucleocytoplasmic β-N-acetylglucosaminidase (O-GlcNAcase; encoded by MGEA5 gene), an enzyme involved in the removal of O-GlcNAc. In this study, relationship between the mRNA expressions of genes coding O-GlcNAc cycling enzymes in breast ductal carcinomas and clinicopathological parameters were analyzed. The results showed that poorly differentiated tumors (grade II and III) had significantly higher OGT expression than grade I tumors. Contrary, MGEA5 transcript levels were significantly lower in grade II and III in comparison with grade I tumors. The Spearman rank correlation showed the expressions of OGT and MGEA5 in breast cancer was negatively correlated (r = −0.430, P = 0.0002). Lymph node metastasis status was significantly associated with decreased MGEA5 mRNA expression. This result suggests that elevation in O-GlcNAc modification of proteins may be implicated in breast tumor progression and metastasis.

Hyper-O-GlcNAcylation Is Anti-apoptotic and Maintains Constitutive NF-κB Activity in Pancreatic Cancer Cells

“…We also observe that in all PDAC cell lines examined (MiaPaCa-2, BxPC-3, Capan-1, Panc-1, HPAFII) hyper-O-GlcNAcylation is associated with up-regulated OGT levels and down-regulated OGA levels compared with non-transformed pancreatic epithelial HPDE cells. In agreement with our findings in PDAC, we and other groups have now observed elevated O-GlcNAcylation, OGT overexpression, and reduced OGA expression in a variety of human malignancies ranging from nonsolid tumor chronic lymphocytic leukemia (37) to breast (8,38), prostate (9), lung (39), colorectal (39), and liver (40). These data indicate that hyper-O-GlcNAcylation could be a general hallmark of cancer.…”

O-Linked β-N-Acetylglucosaminylation (O-GlcNAcylation) in Primary and Metastatic Colorectal Cancer Clones and Effect of N-Acetyl-β-d-glucosaminidase Silencing on Cell Phenotype and Transcriptome

“…Increased O-GlcNAcylation and elevated OGT expression were also found in several breast cancer cell lines (7). Moreover, lymph node metastases of ductal breast carcinomas were associated with a decreased OGA transcript level, and grade II and III tumors showed higher OGT expression and lower OGA expression compared with grade I tumors (12). Phenotypically, the two WT metastatic clones showed distinct cell morphologies and growth (Fig.…”

Critical Role of O-Linked β-N-Acetylglucosamine Transferase in Prostate Cancer Invasion, Angiogenesis, and Metastasis

“…More recently, expression of the enzyme that removes O-GlcNAcylation, O-GlcNAcase, has been found to be reduced in breast (37) and liver (36) cancer. Knockdown of O-GlcNAcase in liver cancer cells increases total OGlcNAcylation levels and increases the migration and invasion of these cells.…”