Resistance to phorbol ester-induced differentiation in human myeloid leukemia cells: a hypothetic role for the mRNA stabilization process.
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.
Champelovier
Pierre
P
Laboratoire de Dynamique Cellulaire de l'EPHE, UMR CNRS 5525, Université Joseph Fourier, 38000 Grenoble, France.
Pautre
Virginie
V
Elatifi
Michèle
M
Dupré
Isabelle
I
Rostaing
Béatrice
B
Michoud
Annick
A
Berger
François
F
Seigneurin
Daniel
D
D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D018922:HL-60 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D009281:Naphthalenes / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011493:Protein Kinase C / Q000187:drug effects / Q000235:genetics; D064546:Protein Kinase C beta; D020871:RNA Stability; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects / Q000494:pharmacology; D020298:U937 Cells
D018797:Cell Cycle Proteins; D009281:Naphthalenes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D013755:Tetradecanoylphorbol Acetate