NDRG1 contributes to retinoic acid-induced differentiation of leukemic cells

Leuk Res. 2009 Aug;33(8):1108-13. doi: 10.1016/j.leukres.2008.10.016. Epub 2008 Nov 28.


N-Myc downstream-regulated gene 1 (NDRG1) protein has been shown to be up-regulated during leukemic cell differentiation induced by some differentiation-inducing agents such as all-trans retinoic acid (ATRA). However, the potential role of up-regulated NDRG1 in the event is greatly unknown. In this work, we show that inducible NDRG1 expression can drive leukemic U937 cells to undergo differentiation, while the knock-down of NDRG1 expression by specific small interfering RNA significantly antagonizes ATRA-induced differentiation of leukemic cells, proposing the role of NDRG1 in leukemic cell differentiation. Furthermore, our work shows that CCAAT/enhancer-binding protein beta (C/EBPbeta) and PU.1, which are important hematopoiesis-related transcription factors, may act as downstream effectors of NDRG1 in leukemic cell differentiation. Taking together, this study provides direct evidence for the role of NDRG1 protein in myeloid leukemic cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Cycle Proteins / biosynthesis*
  • Cell Differentiation / drug effects*
  • Gene Expression Regulation, Leukemic / drug effects*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leukemia, Myeloid / metabolism*
  • Neoplasm Proteins / biosynthesis*
  • Proto-Oncogene Proteins / metabolism
  • Trans-Activators / metabolism
  • Tretinoin / pharmacology*
  • U937 Cells
  • Up-Regulation / drug effects


  • Antineoplastic Agents
  • CCAAT-Enhancer-Binding Protein-beta
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • Tretinoin