The polycomb group protein Bmi-1 is essential for the growth of multiple myeloma cells

Zainab Jagani, Dmitri Wiederschain, Alice Loo, Dan He, Rebecca Mosher, Paul Fordjour, John Monahan, Michael Morrissey, Yung Mae Yao, Christoph Lengauer, Markus Warmuth, William R. Sellers, Marion Dorsch

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5528-5538
Number of pages11
JournalCancer Research
Volume70
Issue number13
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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