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

Abstract

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.

BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transition

“…The results of our in vitro and in vivo experiments confirmed a negative correlation between BRD7 and YB1. Considering our previous finding that BRD7 is lowly expressed and positively correlated with prognosis in breast cancer samples [8], which is consistent with the results of Nigro et al [7], To gain a more general insight into the association between BRD7 and YB1 in clinical specimens, we used IHC to examine the molecular expression level of YB1 in a total of 220 human breast cancer samples and 43 normal breast samples. The results showed that YB1 was highly expressed in breast cancer, that its expression in clinical stages 3 and 4 was significantly higher than that in stages 1 and 2, and that high levels of YB1 are correlated with poor clinical outcomes of breast cancer patients (Fig.…”

“…Furthermore, a series of rescue experiments confirmed that BRD7 blocks tumor growth, EMT and metastasis through a YB1-mediated malignant phenotype. Importantly, combined with the results of our previous studies [8], clinical data analysis revealed that BRD7 is negatively correlated with YB1 and that low expression of BRD7 combined with high expression of YB1 is an effective marker for poor prognosis and is associated with tumor size, distant metastasis and advanced TNM stage in breast cancer patients.…”

“…A total of 220 breast cancer and 43 normal breast paraffin-embedded samples were collected from the Second Xiangya Hospital of Central South University from November 2001 to September 2012, and this study was approved by Ethics Review Committees/Institutional Review Boards of Central South University.Clinicopathologic features of the breast cancer patients mainly included gender, age, tumor size, node metastasis, distant metastasis, clinical tumor node metastasis (TNM) stage, pathology diagnose, survival time and molecular subtype. The immunohistochemical scores of clinical samples were based on the detailed procedures described in other articles [8].…”

“…BRD7 is usually under expressed and plays a role as a tumor suppressor in many malignant tumors; in addition, it is associated with advanced disease and poor prognosis in cancers such as nasopharyngeal cancer (NPC), breast cancer, ovarian cancer, lung cancer and liver cancer [4][5][6]. Immunohistochemistry (IHC) of breast cancer and normal tissues confirmed that the low expression and mainly nuclear localization of BRD7 is present in tumor tissues and a high level of BRD7 is viewed as a positive prognostic factor [7,8]. BRD7 participates in a myriad of cellular processes, including proliferation inhibition, cell cycle arrest, apoptosis induction, migration and invasion inhibition, embryonic death [6,9].…”

Low expression of pro-apoptotic proteins Bax, Bak and Smac indicates prolonged progression-free survival in chemotherapy-treated metastatic melanoma

“…It needs to, however, be stated that in reverse a large body of literature associates high expression of pro-apoptotic or a low expression of antiapoptotic genes or proteins with better outcome, as would intuitively be expected (see e.g., ref. [48][49][50][51][52][53][54][55][56][57][58][59] ). Overall, it therefore appears that signatures indicative of apoptosis competency or resistance need to be interpreted or studied within the specific disease setting and context.…”