PMID- 10969805
OWN - NLM
STAT- MEDLINE
DCOM- 20000914
LR  - 20171116
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 60
IP  - 16
DP  - 2000 Aug 15
TI  - Induction of retinoic acid receptor-alpha by granulocyte macrophage 
      colony-stimulating factor in human myeloid leukemia cell lines.
PG  - 4544-9
AB  - We reported previously that treatment with all-trans retinoic acid (ATRA) and 
      granulocyte macrophage colony-stimulating factor (GM-CSF) induces differentiation 
      of human myeloblastic leukemia ML-1 cells to granulocytes, whereas treatment with 
      ATRA alone induces practically no differentiation of these cells. To investigate 
      the mechanism of the synergistic effect of these factors, we examined the effect 
      of GM-CSF on retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in 
      ML-1 cells. We reveal that GM-CSF induces the expression of RAR alpha mRNA and 
      protein and stimulates the binding of nuclear proteins to direct repeat 5, a 
      consensus sequence with high affinity for RAR-RXR heterodimers. Furthermore, 
      expression of CD38 mRNA mediated through RAR alpha is induced synergistically by 
      treatment with ATRA + GM-CSF. These results suggest that GM-CSF stimulates 
      transcriptional activity mediated via RAR alpha in ML-1 cells. The induction of 
      RAR alpha by GM-CSF may therefore be a mechanism for stimulation by GM-CSF. The 
      induction of RAR alpha by GM-CSF was also detected in other myeloid leukemia cell 
      lines (THP-1 and KG-1) that showed a synergistic effect similar to that seen in 
      ML-1 cells in response to ATRA + GM-CSF. We also found that GM-CSF induced the 
      expression of RAR alpha in blood cells obtained from patients with acute myeloid 
      leukemia. This activity of GM-CSF may serve as a useful adjunct to 
      differentiation therapy for retinoic acid-nonresponsive leukemias.
FAU - Shimizu, T
AU  - Shimizu T
AD  - Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Science 
      University of Tokyo, Japan.
FAU - Takeda, K
AU  - Takeda K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RARA protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 5688UTC01R (Tretinoin)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 3.2.2.5 (ADP-ribosyl Cyclase)
RN  - EC 3.2.2.5 (CD38 protein, human)
RN  - EC 3.2.2.5 (NAD+ Nucleosidase)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
SB  - IM
MH  - ADP-ribosyl Cyclase
MH  - ADP-ribosyl Cyclase 1
MH  - *Antigens, CD
MH  - Antigens, Differentiation/biosynthesis/genetics
MH  - Antineoplastic Agents/pharmacology
MH  - Cell Differentiation/drug effects
MH  - Drug Synergism
MH  - Gene Expression/drug effects
MH  - Gene Expression Regulation, Leukemic/drug effects
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Granulocytes/cytology/drug effects
MH  - Humans
MH  - Leukemia, Myeloid/*metabolism/pathology
MH  - Membrane Glycoproteins
MH  - NAD+ Nucleosidase/biosynthesis/genetics
MH  - Nuclear Proteins/metabolism
MH  - Protein Binding/drug effects
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Retinoic Acid/*biosynthesis/genetics
MH  - Response Elements/drug effects/physiology
MH  - Retinoic Acid Receptor alpha
MH  - Retinoid X Receptors
MH  - Stimulation, Chemical
MH  - Transcription Factors/biosynthesis/genetics
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured/drug effects
EDAT- 2000/09/02 11:00
MHDA- 2000/09/19 11:01
CRDT- 2000/09/02 11:00
PHST- 2000/09/02 11:00 [pubmed]
PHST- 2000/09/19 11:01 [medline]
PHST- 2000/09/02 11:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2000 Aug 15;60(16):4544-9.