Expression And Significance Of N-acetylglucosaminyltransferase V And Mucin1 In Breast Cancer

Purpose:β1, 6-N-Acetylglucosaminyltransferase-V (GnT-V) catalyzes the addition of complex oligosaccharide side chains to glycoproteins, regulating the expression and function of several proteins involved in tumor metastasis. Numerous studies showed the overexpression of MUC1 in breast cancer. MUC1 is involved with cell signalling, immuno-regulation and inhibition of cell-cell and cell-matrix adhesion. However, studies of the correlation of them in breast cancer are limited. This study was designed to provide a comprehensive assessment on significance of N-acetylglucosaminyltransferase V and mucin1 in breast cancer.Experimental Design: We analyzed GnT-V activity, the expression of MUC1, extrogen receptor(ER), progesterone receptor(PR), and erbB-2(HER2 / neu) on a tissue microarray cohort of 57 breast carcinomas with more than 7-year follow-up and 12 breast benign dieases. Phaseolus Vulgaris leukocytic phytohemagglutinin (LPHA), a lectin specific forβ1, 6-branched oligosaccharides, was used to assay GnT-V activity. The expression levels of MUC1, ER and PR were examined by a detailed immunohistochemical analysis with monoclonal antibody. HER-2 gene amplification was examined by chromogenic in situ hybridization method. The correlation of GnT-V activity, MUC1, ER, PR, and HER-2 expressions were also studyied.Results: The high activity of GnT-V and MUC1 overexpression was observed in most breast cancer (89.47%). It had a significant sense compared with benign breast diease (P < 0.01). Our results show a high degree of positive correlation of the LPHA staining with mucin1(r=0.814, P< 0.01). No distinct difference of GnT-V activity and MUC1 expression was observed in different type, different node status and different staging of breast cancer. The high activity of GnT-V and MUC1 overexpression were not associated with ER or PR or HER-2 positive phenotype. In addition, ER and PR exhibited coassociation(r=0.602), a negative correlation of HER-2 with ER and PR was also observed. Furthermore, LPHA staining, MUC1 expression, oestrogen receptor (ER) phenotype, progestogen receptor (PR) phenotype and HER2/neu expression did not show significant association with disease-related survival. The traditional markers of tumor progression which are large tumor size, positive node status and high tumor stage showed significant association with disease-related survival in our breast tissue microarray.Conclusions: The results suggest thatβ1,6-N-acetylglucosaminyltransferase V activity and the expression of mucin1 was elevated in breast carcinoma when compared with benign dieases. These data show that elevated levels of GnT-V activity and the high expression of MUC1 in breast cancer might be significant for the diagnosis and immunotherapy of breast cancer. The high correlation of GnT-V activity and MUC1 suggests that alterations in protein glycosylation of mucin1 is associated with the increase ofβ1,6 branch point caused by GnT-V...