Expression of N-acetylglucosaminyltransferase V in endometrial cancer correlates with poor prognosis

Abstract

N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyses b1 -6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cell proteins. The present study aimed to investigate GnT-V expression and its prognostic significance in endometrial cancer. N-acetylglucosaminyltransferase V expression was studied by immunohistochemistry in 74 surgically resected endometrial cancers, and the staining intensity was evaluated. High GnT-V expression in tumour cells was found in 43 (58.1%) of the 74 cases, and was positively correlated with advanced patient age, histological grade, and lymph vascular space involvement. Patients with high GnT-V expression had significantly impaired overall survival and progression-free survival (PFS) (P ¼ 0.0041 and P ¼ 0.0023, respectively) compared to patients with low expression of GnT-V. On multivariate analysis, GnT-V expression was an independent prognostic factor for PFS (P ¼ 0.0364). b1 -6 branching of asparagine-linked oligosaccharides was also detected in GnT-V-positive endometrial cancer cells by leukoagglutinating phytohaemagglutinin (L 4 -PHA) staining, and the molecular size of the major glycoproteins recognised by L 4 -PHA was approximately 60 -200 kDa by lectin blot analysis. These results suggested that high GnT-V expression was correlated with an unfavourable clinical outcome, and that GnT-V is involved in the malignant potential of endometrial cancer by increasing the synthesis of b1 -6 branching of asparagine-linked oligosaccharides.

Enhanced Epithelial-Mesenchymal Transition-like Phenotype in N-Acetylglucosaminyltransferase V Transgenic Mouse Skin Promotes Wound Healing

“…GnT-V expression is associated with a poor prognosis in breast cancer (37), colon cancer (14), and endometrial cancer (38). Consistent with these studies, we found that GnT-V was up-regulated in some cases of poorly differentiated invasive squamous skin carcinoma 4 .…”

High expression of N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma

“…Western blot analysis for GnT-IVa protein was performed as previously described (Yamamoto et al , 2007), with an anti-GnT-IVa mAb (M-71; Santa Cruz Biotechnology) diluted 1 : 1000. Immunoreactive proteins were stained using a chemiluminescence detection system (ECL; Amersham, Arlington Heights, IL, USA).…”

“…Immunoprecipitation was performed using 1.5 mg of protein that was extracted from cells with an anti-human β hCG mAb (HCG-60; Santa Cruz Biotechnology) or β 1 integrin mAb (BV7; Abcam, Cambridge, UK), as previously described (Yamamoto et al , 2007). The anti- β hCG mAb and anti- β 1 integrin mAb (MAB2247; Chemicon International, Temecula, CA, USA) were used at a dilution of 1 : 200 and 1 : 1000, respectively, and western blotting and DSA lectin blotting were performed using the above protocol.…”

Poly N-acetyllactosamine substitutions on N- and not O-oligosaccharides or Thomsen–Friedenreich antigen facilitate lung specific metastasis of melanoma cells via galectin-3

“…Expression of these oligosaccharides on several human tumors such as those of breast, colon, esophagus, endometrium and gliomas have been shown to be associated with the metastatic phenotype [9][10][11] . Their expression on several human and murine cancer cell lines has been shown to correlate with the metastatic potential [9].…”