Induction of Apoptosis in Plasma Cells by B Lymphocyte–Induced Maturation Protein-1 Knockdown
| العنوان: | Induction of Apoptosis in Plasma Cells by B Lymphocyte–Induced Maturation Protein-1 Knockdown |
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| المؤلفون: | Fan-Ru Lin, Kuo-I Lin, Fu-Hung Yang, Hsia-Yuan Ying, Hui-Kai Kuo |
| المصدر: | Cancer Research. 67:11914-11923 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Cancer Research, Programmed cell death, Cell cycle checkpoint, Cell Survival, Plasma Cells, Apoptosis, Biology, Small hairpin RNA, Mice, Cell Line, Tumor, medicine, Animals, Humans, RNA, Neoplasm, 3' Untranslated Regions, B-Lymphocytes, Mice, Inbred BALB C, Gene knockdown, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Flow Cytometry, medicine.disease, Cell biology, Gene Expression Regulation, Neoplastic, Repressor Proteins, Oncology, Proteasome, Cell culture, Plasmacytoma, Positive Regulatory Domain I-Binding Factor 1, Multiple Myeloma, Transcription Factors |
| الوصف: | B lymphocyte–induced maturation protein-1 (Blimp-1) is a transcriptional repressor that plays an important role during plasmacytic differentiation and is expressed in normal and transformed plasma cells. We here investigated the importance of continuous Blimp-1 expression. We found that knockdown of Blimp-1 expression by lentiviral vector-delivered short hairpin RNA causes apoptosis in multiple myeloma cell lines and plasmacytoma cells, indicating that continued expression of Blimp-1 is required for cell survival. We examined the mechanism underlying Blimp-1 knockdown-mediated apoptosis and found that the Blimp-1 knockdown neither reversed the phenotypic markers of plasma cells nor caused cell cycle arrest. Instead, our results show that knockdown of Blimp-1 induced the proapoptotic protein Bim, reduced the antiapoptotic protein Mcl-1, and activated caspase-9 and caspase-3. We further link apoptosis in transformed plasma cells mediated by proteasome inhibitors, the effective therapeutic agent for multiple myeloma patients, with reduced expression of Blimp-1. Lastly, we show that Blimp-1–dependent cell survival may act downstream of IFN regulatory factor 4 (IRF4) because IRF4 knockdown leads to down-regulation of Blimp-1 and apoptosis in multiple myeloma cells and plasmacytoma cells. Together, our data suggest that Blimp-1 ensures the survival of transformed plasma cells. [Cancer Res 2007;67(24):11914–23] |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd6f1cb3633d44dd2965a70a646074fc https://doi.org/10.1158/0008-5472.can-07-1868 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fd6f1cb3633d44dd2965a70a646074fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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