Bromodomain-containing protein 7 sensitizes breast cancer cells to paclitaxel by activating Bcl2-antagonist/killer protein

Our previous study demonstrated that bromodomain-containing protein 7 (BRD7) inhibits cell proliferation and tumor growth, restoring the expression of B-cell lymphoma 2 antagonist/killer (Bak) sensitized breast cancer cells to paclitaxel. However, the association between BRD7 and paclitaxel sensitization, as well as BRD7 and Bak in breast cancer remains unknown. In the present study, immunochemical staining was performed to measure the expression of BRD7 and Bak in breast cancer tissues. Cell Counting Kit-8 assay, flow cytometry and tumor xenograft procedures were performed to evaluate the biological role of BRD7 and Bak in breast cancer cells. Western blotting, reverse transcription-quantitative polymerase chain reaction, chromatin immunoprecipitation and luciferase reporter assays were also performed. BRD7 was positively correlated with Bak levels in breast cancer tissues, and the survival rate of patients with low Bak and BRD7 expression was significantly lower than that of patients with high Bak and BRD7 expression. In addition, BRD7 activated Bak promoter activity and induced Bak expression in an indirect manner. Furthermore, ectopic expression of BRD7 inhibited cell proliferation, tumor growth and sensitized cancer cells to paclitaxel, while knockdown of Bak abolished BRD7-mediated inhibitory effects on cell proliferation and paclitaxel sensitization in breast cancer cells whether in vitro and in vivo. The results demonstrated that BRD7 inhibits cell proliferation and sensitizes breast cancer cells to paclitaxel by activating Bak; they also provide promising targets for the diagnosis and treatment of breast cancer.