PMID- 10995005
OWN - NLM
STAT- MEDLINE
DCOM- 20001006
LR  - 20190915
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 14
IP  - 9
DP  - 2000 Sep
TI  - GTP-mediated differentiation of the human K562 cell line: transient 
      overexpression of GATA-1 and stabilization of the gamma-globin mRNA.
PG  - 1589-97
AB  - Induction of specific gene expression may provide an alternative or a support to 
      conventional cytotoxic chemotherapy of cancer, as well as to therapy for sickle 
      cell diseases. In this respect, pharmacological induction of expression of the 
      endogenous gamma-globin gene is a realistic approach to therapy of beta-globin 
      disorders. Erythroid differentiation and inhibition of proliferation of the human 
      CML K562 cell line was induced by guanosine 5'-triphosphate (GTP). The hemoglobin 
      production in cells was correlated to an increase in alpha- and gamma-globin mRNA 
      expression. At the transcriptional level, we showed that both the expression of 
      the major erythroid transcription factor GATA-1 (protein and mRNA) and its 
      binding capacity to the gamma-globin gene promoter was transiently increased. 
      Moreover, GTP moderately stimulated the gamma-globin gene promoter after 48 h of 
      treatment. At the post-transcriptional level, GTP treatment led to a drastic 
      increase of the gamma-globin mRNA half-life. This stabilizing effect of GTP was 
      mediated via the 3'-untranslated region (3'-UTR) of the gamma-globin mRNA. In 
      conclusion, mechanism of GTP-mediated differentiation of K562 cells is linked to 
      an early activation of gamma-globin gene transcription followed by a 
      stabilization of its mRNA.
FAU - Morceau, F
AU  - Morceau F
AD  - Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Centre 
      Universitaire de Luxembourg, France.
FAU - Dupont, C
AU  - Dupont C
FAU - Palissot, V
AU  - Palissot V
FAU - Borde-Chiche, P
AU  - Borde-Chiche P
FAU - Trentesaux, C
AU  - Trentesaux C
FAU - Dicato, M
AU  - Dicato M
FAU - Diederich, M
AU  - Diederich M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Erythroid-Specific DNA-Binding Factors)
RN  - 0 (GATA1 Transcription Factor)
RN  - 0 (GATA1 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 9004-22-2 (Globins)
SB  - IM
MH  - DNA-Binding Proteins/*biosynthesis/genetics
MH  - Erythroid-Specific DNA-Binding Factors
MH  - Erythropoiesis/genetics/*physiology
MH  - GATA1 Transcription Factor
MH  - Gene Expression Regulation, Neoplastic
MH  - Globins/genetics/*metabolism
MH  - Guanosine Triphosphate/*physiology
MH  - Humans
MH  - K562 Cells
MH  - Promoter Regions, Genetic/genetics
MH  - RNA Stability
MH  - RNA, Messenger/metabolism
MH  - Transcription Factors/*biosynthesis/genetics
EDAT- 2000/09/20 11:00
MHDA- 2000/10/14 11:01
CRDT- 2000/09/20 11:00
PHST- 2000/09/20 11:00 [pubmed]
PHST- 2000/10/14 11:01 [medline]
PHST- 2000/09/20 11:00 [entrez]
AID - 10.1038/sj.leu.2401890 [doi]
PST - ppublish
SO  - Leukemia. 2000 Sep;14(9):1589-97. doi: 10.1038/sj.leu.2401890.