Document Detail


Gene profiling of growth factor independence 1B gene (Gfi-1B) in leukemic cells.
MedLine Citation:
PMID:  18224412     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages, the naturally Gfi-1B overexpressing cell line K562 was cultured in the presence of Gfi-1B target-specific small interfering RNA (siRNA). SiRNA treatment significantly knocked down Gfi-1B expression with an efficiency of nearly 90%. Analysis of the siRNA silencing protocol by colony-forming units ensured that it was not cytotoxic. Samples from Gfi-1B overexpressing cells and cells with knocked-down Gfi-1B were analyzed by oligonucleotide microarray technology and based upon rigorous statistical analysis of the data; relevant genes were chosen for confirmation by reserve transcriptase-polymerase chain reaction, including MYC/MYCBP and CDKN1A. Interestingly, transcripts within components of the signalling cascade of immune cells (PLD1, LAMP1, HSP90, IL6ST), of the tyrosine kinase pathway (TPR, RAC3) and of the transcription factors (RAC3, CEP290, JEM-1, ATR, MYC, SMC3, RARA, RBBP6) were found to be differentially expressed in Gfi-1B overexpressing cells compared to controls. Individual genes such as ZDHHC17, DMXL1, ZNF292 were found to be upregulated in Gfi-1B overexpressing cells. In addition, down-regulated transcripts showed cell signaling transcripts for several chemokine gene members including GNAL, CXCL5, GNL3L, GPR65, TMEM30, BCL11B and transcription factors (GTF2H3, ATXN3). In conclusion, several essential cell signalling factors, as well as transcriptional and post-translational regulation genes were differentially expressed in cells that overexpressed Gfi-1B compared to control cells with knocked-down Gfi-1B. Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations.
Authors:
Michael Koldehoff; Johannes L Zakrzewski; Ludger Klein-Hitpass; Dietrich W Beelen; Ahmet H Elmaagacli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-06
Journal Detail:
Title:  International journal of hematology     Volume:  87     ISSN:  0925-5710     ISO Abbreviation:  Int. J. Hematol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-28     Completed Date:  2008-10-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39-47     Citation Subset:  IM    
Affiliation:
Department of Bone Marrow Transplantation, University Hospital of Duisburg-Essen, Essen, Germany. michael.koldehoff@uni-duisburg-essen.de
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MeSH Terms
Descriptor/Qualifier:
Case-Control Studies
Gene Expression Profiling*
Hematopoiesis / genetics*
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
Oligonucleotide Array Sequence Analysis*
Proto-Oncogene Proteins / genetics*,  metabolism
Repressor Proteins / genetics*,  metabolism
Signal Transduction / genetics
Tumor Cells, Cultured
Up-Regulation
Chemical
Reg. No./Substance:
0/GFI1B protein, human; 0/Proto-Oncogene Proteins; 0/Repressor Proteins

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