The Role Of ST6GalNAacII In The Invasion Of Breast Carcinoma And Its Clinical Significance

Objective:The objective of this study is to explore the role of ST6GalNAcII and PI3K/Akt-NFkB signal pathway in the invasion process of breast carcinoma. In attention, we also clarify the relationship between ST6GalNAcII and the clinical characteristics of breast carcinoma. All of these are helpful to the diagnosis and treatment of breast carcinoma.Methods:RT-PCR?western blot analysis% vitro extracellular matrix invasion assay and tumorigenicity assay were used to analysis the expression level of ST6GalNAc? and potential signaling pathways and mechanism of it in the invasion process of breast carcinoma. (1) The expression of ST6GalNAc? genes was reduced by ST6GalNAc?-shRNA, and the expression level of ST6GalNAc? protein and invasion of breast cancer cells were explored by vitro extracellular matrix invasion assay. (2) 45 female nude mice,5-week-old, were randomly divided into three groups. MDA-MB-231 cells which were dealt with ST6GalNAc? shRNA were injected into the left flank of the mouse. After 3 weeks, the mice bore palpable tumors which were used for further research. The mice in the control group were treated with the same methods. Besides, we also analysis the the expression level of ST6GalNAc? in mice tumor tissues by immunohistochemical study. (3) The key factor of phosphatidylinositol-3-kinase (PI3K)/Akt-NFkB signaling pathway was studied after ST6GalNAc? expression was down regulated by shRNA. After PI3K and Akt were inhibited by LY294002 and Akt siRNA, we studied the relationship between PI3K/Akt signal pathway and the invasion of MDA-MB-231 cells. Breast cancer tissue samples and transitional samples (3 cm from the tumor edge) were collected from the same 101 patients from July in 2011 to July in 2013 at the Second Affiliated Hospital of Dalian Medical University. The ST6GalNAc? protein expression in these tumor tissues and its relationship with the invasiveness of breast carcinoma were analyzed. We also analysis the expression level of ST6GalNAcII in these tumor tissues by immunohistochemical study.Results:The expression of ST6GalNAcII was higher in the highly aggressive MDA-MB-231 cells than in low-invasive MCF-7 cells. The changes of the expression of ST6GalNAcII in MDA-MB-231 cells caused the low invasion ability of MDA-MB-231 cells. The tumorigenicity in the nude mice was also suppressed. Interestingly, when the expression of ST6GalNAcII was reduced, the protein phosphorylation level in signaling pathway was also decreased. In patients with breast carcinoma, age and distant metastasis were not significantly related with the ST6GalNAcII protein expression (P>0.05). However, the histological grade, lymph node metastasis and clinical stage were significantly related with the ST6GalNAc? protein expression (P< 0.05).Conclusion:(1) ST6GalNAc? played an important role in the invasion of breast carcinoma cells. The effect was likely to be through the PI3K/Akt signaling pathway. (2) The abnormal expression of ST6GalNAc? was related with the histological grade, lymph node metastasis and clinical stage of breast cancer.