title: RNAi-mediated silencing of the Bmi-1 gene causes growth inhibition and enhances doxorubicin-induced apoptosis in MCF-7 cells.
abstract: The oncogene Bmi-1 is a member of the Polycomb group gene family. Its expression is found to be greatly increased in a number of malignant tumors including breast cancer. This could suggest Bmi-1 as a potent therapeutic target. In this study, RNAi was introduced to down-regulate the expression of Bmi-1 in a highly malignant breast adenocarcinoma cell line, MCF-7. A thorough study of the biological behavior and chemosensitivity changes of the MCF-7 cells was carried out in context to the therapeutic potential of Bmi-1. The results obtained indicated that siRNA targeting of Bmi-1 could lead to an efficient and specific inhibition of endogenous Bmi-1 activity. The mRNA and protein expression of Bmi-1 were determined by RT-PCR and Western blot, respectively. Furthermore, silencing of Bmi-1 resulted in a drastic inhibition of the growth of MCF-7 cells as well as G(1) /S phase transition. The number of target cells was found to increase in phase G (0) /G (1) and decrease in the S phase, but no increase in the basal level of apoptosis was noticed. On the other hand, a reduction in the expression of cyclin D1 and an increase in the expression of p21 were also noticed. Silencing of Bmi-1 made the MCF-7 cells more sensitive to the chemotherapeutic agent doxorubicin and induced a significantly higher percentage of apoptotic cells. Here, we report on a study regarding the RNAi-mediated silencing of the Bmi-1 gene in breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing PR China.
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Wu
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: You-Quan
authors.initials: YQ
authors.lastname: Bu
authors.forename: Joyeeta
authors.initials: J
authors.lastname: Sengupta
authors.forename: Hong-Juan
authors.initials: HJ
authors.lastname: Cui
authors.forename: Fa-Ping
authors.initials: FP
authors.lastname: Yi
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Chen-Fu
authors.initials: CF
authors.lastname: Yuan
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Shi
authors.forename: Fang-Zhou
authors.initials: FZ
authors.lastname: Song