The Expression And Function Of Ndc80 In Pancreatic Carcinoma

OBJECTIVE: Pancreatic cancer is a lethal malignancy.A majority of patients have been diagnosed with locally advanced or metastatic because of the lack of easily observable symptoms,and only 15%-20% of the patients have the chance for surgery and the rest could receive adjuvant therapies.Even though new antitumor drugs and techniques have been developed,the prognosis for these patients remains poor.Therefore,further research of molecule mechanisms and novel therapeutic strategies should be urgently required.Ndc80,one of four proteins of the outer kinetochore Ndc80 complex,is involved in the tumorigenesis of a variety of cancers.In this study,we focused on that Ndc80 is overexpressed in human pancreatic cancer and investigates the role of Ndc80-knockdown in pancreatic cancer cells proliferation,and evaluated the correlation with prognosis of pancreatic cancer.MATERIALS AND METHODS: We determined the expression levels of Ndc80 on both m RNA and protein levels in fresh pancreatic cancer tissues and cells(Panc-1,Sw1990 and Bxpc-3)by quantitative real-time polymerase chain reaction and immunoblotting,respectively.Furthermore,protein level of Ndc80 was identified using immunochemistry in paraffin-embedded tumor specimen,with correlation between Ndc80 expression and various clinicopathological parameters evaluated.The role of Ndc80 in pancreatic cancer cells(Panc-1)growth was investigated by lentivirus-mediated silencing of Ndc80.The effect of Ndc80 deletion on cell proliferation was analyzed by MTT assay and clone formation assay,while cell cycle distributions and apoptosis were analyzed by flow cytometry.RESULTS: The m RNA and protein of Ndc80 were overexpressed in pancreatic cancer tissues and cells.The statistical analysis based on immunohistochemical evaluation suggested that Ndc80 overexpression was significantly associated with clinicopathological parameters including pathological T staging and N staging,which may be served as an predictor for poor outcomes.The silencing of Ndc80 in Panc-1 cells could suppress cell proliferation and colony formation.Furthermore,the Ndc80-si RNA infected Panc-1 cells lead to cell cycle arrest at G2/M phase and induction of apoptosis.CONCLUSION: These results demonstrated that Ndc80 plays an essential role in the proliferation mechanism of pancreatic cancer,and might serve as potential therapeutic target for treatment of pancreatic cancer.