Blocking the Notch signal transduction pathway promotes tumor growth in breast cancer by promoting the expression of suppressible inflammatory factors.

Abstract

BackgroundBreast cancer is the most common malignant tumor among all female tumors. It seriously affects the health and lives of patients, and poses a significant economic burden. The study of the molecular mechanisms of breast cancer occurrence, proliferation and growth and development is of great clinical significance.MethodsNotch1 knockout mice were obtained by gene targeting. The expression of inflammatory factor arginase-1 in each group of tumors was observed by immunofluorescence staining. Semi-quantitative detection of Notch1, Arginase-1, and proteins belonging to the PI3K-AKT pathway by western blot. The expression level of interleukin-3 (IL-3), and IL-4 in serum was quantified by enzyme linked immunosorbent assay (ELISA).ResultsIn this study, Notch1 knockout in mice promoted the cell proliferation of breast cancer. Further study on molecular mechanisms demonstrated that the increased cell proliferation resulted from the activation of the PI3K-AKT signal transduction pathway. In addition, the expression of the M2-type inflammatory factor arginase-1 significantly increased, which was dependent on the activation of the PI3K-AKT pathway, indicating that Notch1 knockout in mice promoted the polarization of tumor-associated macrophages (TAMs). Consistent with this, IL-3 and IL-4 expression also significantly increased in the serum of Notch1 knockout mice.ConclusionsAccording to our results, Notch1 knockout in mice significantly promoted the cell proliferation of breast cancer, not only by activating the PI3K-AKT pathway, but also by promoting the polarization of TAMs towards the M2-type phenotype.