Department of Breast Surgery, Qilu Hospital, Shandong University, Wenhua Xi Road No.107, Ji'nan 250012, China.
Cell Death Dis. 2013 Aug 8;4(8):e757. doi: 10.1038/cddis.2013.290.
In our previous study, we demonstrated that the BRCC2 (breast cancer cell 2) gene is a proapoptotic molecule that interacts with Bcl-X(L). BRCC2 downregulation is associated with poor disease-free and overall survival in breast cancer. In this study, we aimed to investigate the role of BRCC2 in tumor suppression in breast cancer. In clinical breast cancer samples, we found that BRCC2 expression was significantly downregulated in cancer lesions compared with paired normal breast tissues. By silencing or overexpressing BRCC2 in breast cancer cells, we found that BRCC2 could inhibit cell growth and metastasis in vitro. An in vivo assay showed that BRCC2 not only dramatically inhibited breast cancer cell xenograft formation and growth but also inhibited breast cancer cell metastasis in a lung metastasis model. Moreover, we demonstrated that BRCC2 inhibited breast cancer metastasis via regulation of the Akt pathway. Thus, our study provided evidence that BRCC2 functions as a novel tumor suppressor in breast cancer and may be a potential therapeutic target for breast cancer management.
在我们之前的研究中,我们证明了 BRCC2(乳腺癌细胞 2)基因是一种促凋亡分子,与 Bcl-X(L)相互作用。BRCC2 的下调与乳腺癌无病生存期和总生存期不良相关。在这项研究中,我们旨在研究 BRCC2 在乳腺癌肿瘤抑制中的作用。在临床乳腺癌样本中,我们发现与配对的正常乳腺组织相比,BRCC2 在癌症病变中的表达显著下调。通过在乳腺癌细胞中沉默或过表达 BRCC2,我们发现 BRCC2 可以抑制体外细胞生长和转移。体内实验表明,BRCC2 不仅能显著抑制乳腺癌细胞异种移植的形成和生长,还能抑制肺癌转移模型中的乳腺癌细胞转移。此外,我们证明 BRCC2 通过调节 Akt 通路抑制乳腺癌转移。因此,我们的研究提供了证据,证明 BRCC2 在乳腺癌中作为一种新的肿瘤抑制因子发挥作用,可能是乳腺癌治疗的潜在靶点。