The study of the relationship between Notch signal transduction pathway and polycomb protein Bmi1 in colorectal caner cells

Abstract

14501 Background: As is known the polycomb group protein BMI1 has been shown to support normal stem cell proliferation via its putative stem cell factor function. However, the potential molecular mechanism of BMI1 act as a cancer stem cell factor may also promote cancer development is unclear. In this study we demonstrated for the first time that Notch signal transduction pathway regulating expression of Bmi1 in colorecta caner cells and investigate the Notch1 mRNA and Bmi1 mRNA level in human colorectal cancer samples and their correlation with clinicopathological parameters of colorectal cancer. Methods and Results: We assessed Notch1 and Bmi1 mRNA in 50 cases of colorectal cancer and adjacent normal tissue by RT-PCR. The immunohistochemistry was used to determine the expression of ICN and in the 50 tissues of colorectal cancer and normal mucosa. Bmi1 SW480 cells were treated with DAPT (g-secretase inhibitor) at different times. MTT assay and flow cytometry were used to measure the proliferation and apoptosis of SW480 cells. The expression of ICN, Bmi1 were measured by western blot. Notch1 and Bmi1 mRNA level were increased in colorectal cancer compared with adjacent normal mucosa (P<0.05), the median values were 1.97-fold, 1.88-fold, respectively. It was found that overexpression of Notch1 and Bmi1 was related to differentiation and lymph nodes metastasis in colorectal cancer (P<0.05). The correlation between Notch1 and Bmi1 mRNA level, ICN and Bmi1 protein level are significant at the 0.01 level. Treating SW480 with DAPT, resulted in significant growth inhibition, apoptosis induction and downregulation of ICN and Bmi1. Conclusion: Our results show that overexpression of Notch1 and Bmi1 may play a critical role in the development of colorectal cancer. Notch1 signal transduction pathway regulating expression of Bmi1 in colorectal cancer cells.Blockade of Notch1 signal pathway can inhibit proliferation and accelerate apoptosis of colorectal cancer. [Key words] Colorectal cancer; BMI1; Signal transducers and activators of transcription3; Western blotting No significant financial relationships to disclose.