PMID- 10330422
OWN - NLM
STAT- MEDLINE
DCOM- 19990607
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 103
IP  - 10
DP  - 1999 May 15
TI  - CCAAT/enhancer binding protein epsilon is a potential retinoid target gene in
      acute promyelocytic leukemia treatment.
PG  - 1399-408
AB  - The CCAAT/enhancer binding protein epsilon (C/EBPepsilon) is a nuclear
      transcription factor expressed predominantly in myeloid cells and implicated as a
      potential regulator of myeloid differentiation. We show that it was rapidly
      induced in the acute promyelocytic leukemia (APL) cell line NB4 during
      granulocytic differentiation after exposure to retinoic acid (RA). Our data
      suggest that induction of C/EBPepsilon expression was through the retinoic acid
      receptor alpha (RARalpha) pathway. Reporter gene studies showed that C/EBPepsilon
      promoter/enhancer activity increased in a retinoid-dependent fashion via the
      retinoic acid response element (RARE) present in the promoter region of
      C/EBPepsilon. The RA-induced expression of C/EBPepsilon markedly increased in
      U937 myelomonoblasts that were induced to express promyelocytic leukemia/RARalpha
      (PML/RARalpha), but not in those induced to express promyelocytic leukemia zinc
      finger/RARalpha (PLZF/RARalpha). In retinoid-resistant APL cell lines,
      C/EBPepsilon either is not induced or is induced only at very high concentrations
      of RA (>/=10(-6) M). In addition, forced expression of C/EBPepsilon in the U937
      myelomonoblastic leukemia cells mimicked terminal granulocytic differentiation,
      including morphologic changes, increased CD11b/CD66b expression, and induction of
      secondary granule protein expression. Our data strongly suggest that C/EBPepsilon
      is a downstream target gene responsible for RA-induced granulocytic
      differentiation of APL cells.
FAU - Park, D J
AU  - Park DJ
AD  - Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of
      California-Los Angeles School of Medicine, Los Angeles, California 90048, USA.
      parkd@ucla.edu
FAU - Chumakov, A M
AU  - Chumakov AM
FAU - Vuong, P T
AU  - Vuong PT
FAU - Chih, D Y
AU  - Chih DY
FAU - Gombart, A F
AU  - Gombart AF
FAU - Miller, W H Jr
AU  - Miller WH Jr
FAU - Koeffler, H P
AU  - Koeffler HP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Retinoids)
RN  - 5688UTC01R (Tretinoin)
SB  - AIM
SB  - IM
CIN - J Clin Invest. 1999 May 15;103(10):1367-8. PMID: 10330417
MH  - CCAAT-Enhancer-Binding Proteins
MH  - Cell Differentiation/drug effects/genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Drug Resistance/genetics
MH  - Enhancer Elements, Genetic
MH  - Gene Expression/drug effects
MH  - Genes, Reporter
MH  - Humans
MH  - Leukemia, Promyelocytic, Acute/*drug therapy/*genetics/metabolism
MH  - Nuclear Proteins/*genetics
MH  - Promoter Regions, Genetic
MH  - Receptors, Retinoic Acid/metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Retinoids/*therapeutic use
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
MH  - U937 Cells
PMC - PMC408448
EDAT- 1999/05/20 06:00
MHDA- 2001/03/28 10:01
CRDT- 1999/05/20 06:00
PHST- 1999/05/20 06:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/05/20 06:00 [entrez]
AID - 10.1172/JCI2887 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 May 15;103(10):1399-408. doi: 10.1172/JCI2887.