Document Detail


Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells.
MedLine Citation:
PMID:  16418324     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Translational regulation by oncogenic proteins may be a rapid and efficient mechanism to modulate gene expression. We report here the identification of the CEBPB gene as a target of translational regulation in myeloid precursor cells transformed by the BCR/ABL oncogene. Expression of CEBPB was repressed in 32D-BCR/ABL cells and reinduced by imatinib (STI571) via a mechanism that appears to depend on expression of the CUG-repeat RNA-binding protein CUGBP1 and the integrity of the CUG-rich intercistronic region of c/ebpbeta mRNA. Constitutive expression or conditional activation of wild-type CEBPB induced differentiation and inhibited proliferation of 32D-BCR/ABL cells in vitro and in mice, but a DNA binding-deficient CEBPB mutant had no effect. The proliferation-inhibitory effect of CEBPB was, in part, mediated by the CEBPB-induced GADD45A gene. Because expression of CEBPB (and CEBPA) is low in the blast crisis (BC) stage of chronic myelogenous leukemia (CML) and is inversely correlated with BCR/ABL tyrosine kinase levels, these findings point to the therapeutic potential of restoring C/EBP activity in CML-BC and, perhaps, other types of acute leukemia.
Authors:
Clara Guerzoni; Michela Bardini; Samanta A Mariani; Giovanna Ferrari-Amorotti; Paolo Neviani; Maria Luisa Panno; Ying Zhang; Robert Martinez; Danilo Perrotti; Bruno Calabretta
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-01-17
Journal Detail:
Title:  Blood     Volume:  107     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-04     Completed Date:  2006-06-14     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4080-9     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Bone Marrow Cells / cytology*,  physiology
CCAAT-Enhancer-Binding Protein-beta / genetics*
Cell Differentiation
Cells, Cultured
Fusion Proteins, bcr-abl / genetics*
Gene Expression Regulation
Humans
Luciferases / genetics
Open Reading Frames
Protein Biosynthesis
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Trinucleotide Repeats
Grant Support
ID/Acronym/Agency:
CA 95111/CA/NCI NIH HHS; CA 95512/CA/NCI NIH HHS; P01 78890//PHS HHS; R01 CA095512/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-beta; 0/RNA, Messenger; EC 1.13.12.-/Luciferases; EC 2.7.10.2/Fusion Proteins, bcr-abl
Comments/Corrections

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