The Polycomb Group Protein Bmi-1 Is Essential for the Growth of Multiple Myeloma Cells

被引：51

作者：

Jagani, Zainab ^{[1
]}

Wiederschain, Dmitri ^{[1
]}

Loo, Alice ^{[1
]}

He, Dan ^{[1
]}

Mosher, Rebecca ^{[1
]}

Fordjour, Paul ^{[1
]}

Monahan, John ^{[1
]}

Morrissey, Michael ^{[1
]}

Yao, Yung-Mae ^{[1
]}

Lengauer, Christoph ^{[1
]}

Warmuth, Markus ^{[1
]}

Sellers, William R. ^{[1
]}

Dorsch, Marion ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, Cambridge, MA USA

来源：

CANCER RESEARCH | 2010年 / 70卷 / 13期

关键词：

BCL-2; FAMILY; INK4A-ARF LOCUS; TRANSGENIC MICE; SELF-RENEWAL; H-RAS; C-MYC; CANCER; APOPTOSIS; PATHWAY; BIM;

D O I：

10.1158/0008-5472.CAN-09-4229

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Bmi-1 is a member of the Polycomb group family of proteins that function in the epigenetic silencing of genes governing self-renewal, differentiation, and proliferation. Bmi-1 was first identified through its ability to accelerate c-Myc-induced lymphomagenesis. Subsequent studies have further supported an oncogenic role for Bmi-1 in several cancers including those of the breast, lung, prostate, and brain. Using a stable and inducible shRNA system to silence Bmi-1 gene expression, we show a novel role for Bmi-1 in regulating the growth and clonogenic capacity of multiple myeloma cells both in vitro and in vivo. Moreover, to elucidate novel gene targets controlled by Bmi-1, global transcriptional profiling studies were performed in the setting of induced loss of Bmi-1 function. We found that the expression of the proapoptotic gene Bim is negatively regulated by Bmi-1 and that Bim knockdown functionally rescues the apoptotic phenotype induced upon loss of Bmi-1. Therefore, these studies not only highlight Bmi-1 as a cancer-dependent factor in multiple myeloma, but also elucidate a novel antiapoptotic mechanism for Bmi-1 function involving the suppression of Bim. Cancer Res; 70(13); 5528-38. (C)2010 AACR.

引用

页码：5528 / 5538

页数：11

共 51 条

[1] Perturbation of B and T cell development and predisposition to lymphomagenesis in E mu Bmi1 transgenic mice require the Bmi1 RING finger [J].