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Titolo:
MODULATION OF MESSENGER-RNA EXPRESSION OF A NOVEL HUMAN MYELOID-SELECTIVE CCAAT ENHANCER BINDING-PROTEIN GENE (C/EBP-EPSILON)/
Autore:
CHIH DY; CHUMAKOV AM; PARK DJ; SILLA AG; KOEFFLER HP;
Indirizzi:
UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,DIV HEMATOL ONCOL,SCH MED,DEPT MED LOS ANGELES CA 90048 UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,DIV HEMATOL ONCOL,SCH MED,DEPT MED LOS ANGELES CA 90048
Titolo Testata:
Blood
fascicolo: 8, volume: 90, anno: 1997,
pagine: 2987 - 2994
SICI:
0006-4971(1997)90:8<2987:MOMEOA>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROMYELOCYTIC LEUKEMIA-CELLS; LEUCINE ZIPPER PROTEINS; RETINOIC ACID; T(15-17) TRANSLOCATION; MOLECULAR ANALYSIS; FAMILY MEMBERS; MESSENGER-RNA; NB4 CELLS; DIFFERENTIATION; LINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
D.Y. Chih et al., "MODULATION OF MESSENGER-RNA EXPRESSION OF A NOVEL HUMAN MYELOID-SELECTIVE CCAAT ENHANCER BINDING-PROTEIN GENE (C/EBP-EPSILON)/", Blood, 90(8), 1997, pp. 2987-2994

Abstract

Human C/EBP epsilon is a newly cloned gene coding for a CCAAT/enhancer binding protein that may be involved in the regulation of myeloid differentiation. Our studies showed that levels of C/EBP epsilon mRNA were markedly increased in NB4 cells (promyelocytic leukemia line), because they were induced by 9-cis retinoic acid (9-cis RA) to differentiate towards granulocytes. Accumulation of C/EBP epsilon mRNA occurred as early as 1 hour after exposure of NB4 cells to 9-cis RA (5 x 10(-7) mol/L); and at 48 hours, levels were increased by 5.1-fold. Dose-response studies showed that 10(-7) to 10(-6) mol/L 9-cis RA (12 hours) resulted in peak levels of C/EBP epsilon mRNA; but even 10(-10) mol/L 9-cis RA increased levels of these transcripts. NB4 cells pulse-exposed (30 minutes) to all-trans retinoic acid (ATRA), washed, and cultured (3days) with either dimethylsulfoxide (DMSO) or hexamethylene bisacetamide (HMBA) had a prominent increase in levels of C/EBP epsilon mRNA and an increase in granulocytic differentiation, but exposure to either DMSO or HMBA alone had no effect on base levels of C/EBP epsilon and did not induce differentiation. Macrophage-differentiation of NB4 reduced levels of C/EBP epsilon mRNA. Nuclear run-off assays and half-life studies showed that accumulation of C/EBP epsilon mRNA by 9-cis RA wasdue to enhanced transcription. Furthermore, this C/EBP epsilon mRNA accumulation did not require synthesis of new protein factors because 9-cis RA induced C/EBP epsilon mRNA accumulation in the absence of new protein synthesis. ATRA also induced expression of C/EBP epsilon protein in NB4 cells, as shown by Western blotting. In contrast to the increase of C/EBP epsilon in 9-cis RA-mediated granulocytic differentiation, the DMSO-induced differentiation of HL-60 cells down the granulocytic pathway was associated with an initial reduction of C/EBP epsilon mRNA levels. In summary, we have discovered that expression of C/EBP epsilon mRNA is markedly enhanced as the NB4 promyelocytes are induced by retinoids to differentiate towards granulocytes. This induction of C/EBP epsilon mRNA expression is transcriptionally mediated and occurs in the absence of synthesis of additional protein factors. We suspect that the C/EBP epsilon promoter/enhancer contains a retinoic acid-response element that is directly stimulated by retinoids. (C) 1997 by TheAmerican Society of Hematology.

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Documento generato il 28/11/20 alle ore 00:59:40