BRCC2 inhibits breast cancer cell growth and metastasis in vitro and in vivo via downregulating AKT pathway.
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.
Department of Breast Surgery, Qilu Hospital, Shandong University, Wenhua Xi Road No.107, Ji'nan 250012, China.
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D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D051058:Oncogene Protein v-akt