Resistance to phorbol ester-induced differentiation in human myeloid leukemia cells: a hypothetic role for the mRNA stabilization process

Leuk Res. 2006 Nov;30(11):1407-16. doi: 10.1016/j.leukres.2006.04.006. Epub 2006 Jun 6.


UM384 cells, derived from the human myeloid leukemia U937 cell line, fail to differentiate in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). Using cDNA microarray and real-time quantitative PCR (RT-QPCR) approaches, we observed a difference in the response to TPA treatment: all the genes from U937 cells were continuously modulated from 2 to 24h. In UM384 cells, 60% of the genes were transiently modulated at 2h, then returned to control levels at 24h. Moreover, HuR, an AU-rich element-binding protein (ARE-BP), was differentially located in the two cell lines. Therefore, a defect of mRNA stabilization could be responsible for the resistance of UM384 cells to TPA-induced differentiation, suggesting a possible role for the post-transcriptional regulation in the leukemogenesis.

MeSH terms

  • Cell Cycle Proteins / drug effects
  • Cell Cycle Proteins / genetics
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm*
  • Gene Expression Profiling
  • HL-60 Cells
  • Humans
  • Intercellular Adhesion Molecule-1 / drug effects
  • Intercellular Adhesion Molecule-1 / genetics
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / pathology*
  • Naphthalenes / pharmacology
  • Oligonucleotide Array Sequence Analysis / methods
  • Protein Kinase C / drug effects
  • Protein Kinase C / genetics
  • Protein Kinase C beta
  • RNA Stability*
  • RNA, Messenger / drug effects*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Structure-Activity Relationship
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology
  • U937 Cells


  • Cell Cycle Proteins
  • Naphthalenes
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Protein Kinase C
  • Protein Kinase C beta
  • Tetradecanoylphorbol Acetate