Expression And Role Of Notch1 In Breast Cancer Tissue And Its Effect On Brain Metastasis

Objective: 1.To investigate the expression level of Notch1 receptor in breast cancer tissues and its correlation with clinicopathologic features and prognosis,and comprehensively analyze its clinical significance and prognostic value.2.Through in vitro cell experiments to study the effects of Notch1 expression on the proliferation,movement,migration and invasion of breast cancer cells as well as the ability to adhere and cross the blood-brain barrier,and to explore the effects of Notch1 on breast cancer brain metastasis,so as to provide theoretical and clinical basis for whether Notch1 can become a potential therapeutic target for breast cancer brain metastasis.Methods: 1.The expression of Notch1 receptor protein in 183 cases of breast cancer and47 cases of adjacent normal breast tissue was detected by immunohistochemistry.2.Lentivirus infection technique was used to construct Notch1 stable interference cell lines and Notch1 overexpression cell lines on MDA-MB-231 cells,and the expression level of Notch1 was detected by q PCR and Western Blot.The effects of Notch1 on the proliferation,movement,migration and invasion of breast cancer cells were detected by CCK-8 experiment,cell scratch test and transwell technique.Finally,the model of blood-brain barrier in vitro was established,and the ability of breast cancer cells to adhere to and cross the blood-brain barrier after the change of Notch1 expression was detected by transwell technique.Results: 1.Immunohistochemical results showed that the positive expression rate of Notch1 protein in breast cancer tissues was significantly higher than that in adjacent tissues(χ2=17.475,P <0.001).2.The high expression of Notch1 in breast cancer tissues was correlated with lymph node metastasis(χ2=13.720,P <0.001)and TNM stage(χ2=14.688,P<0.001).Results of survival curve analysis showed that the overall survival time of breast cancer patients with high Notch1 expression was significantly lower than that of patients with low or no Notch1 expression(P <0.05),suggesting that high Notch1 expression is an independent prognostic indicator of breast cancer.3.Compared with the control group,the ability of proliferation,movement,migration and invasion of cells treated with Notch1 interference was decreased(P <0.05),while that of cells treated with Notch1 overexpression enhanced(P <0.05).4.In vitro blood-brain barrier model showed that the number of cells adhering to and crossing the blood-brain barrier in the Notch1 interference group was lower than that in the control group(P <0.05),while the number of cells adhering to and crossing the blood-brain barrier in the Notch1 overexpression group was higher than that in the control group(P <0.05).Conclusion: The results of this study show that Notch1 plays an important role in tumorigenesis.The expression of Notch1 is negatively correlated with the survival of breast cancer patients,which can be used as a biomarker for the prognosis of breast cancer.Notch1 can promote the ability of breast cancer cells to proliferate,move,migrate and invade,as well as the ability of cancer cells to adhere to and cross the blood-brain barrier.In the future,Notch1 is expected to become a new therapeutic target for brain metastasis of breast cancer.