Document Detail


Tetracycline-induced expression of an anti-c-Myb single-chain antibody and its inhibitory effect on proliferation of the human leukemia cell line K562.
MedLine Citation:
PMID:  10678368     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ablation of c-Myb function might be an effective approach for the therapy of chronic myelogenous leukemia or other c-myb-dependent malignancies. To this end, we have previously used an intracellular anti-c-Myb single-chain antibody (sFv) to achieve the functional knockout of the c-Myb oncoprotein. In this study, we have employed a tetracycline-inducible system to control the expression of the sFv. A nuclear-localizing form of an anti-c-Myb sFv was cloned into a tet-regulated plasmid vector. Using a transient expression system in COS-1 cells, we observed that doxycycline (Dox) induced expression of the sFv in a dose-dependent manner, and that the sFv was localized mainly in the nucleus. The Dox-induced anti-c-Myb sFv also inhibited the transactivating activity of c-Myb in a dose-dependent manner. We subsequently confirmed the Dox-induced expression of the sFv in the leukemia cell line K562. Proliferation of the target leukemia cells was also inhibited. These results suggest that the anti-c-Myb sFv may represent a viable method for gene therapy of c-myb-dependent hematopoietic malignancies.
Authors:
K Kasono; Y Heike; J Xiang; A Pich?; H G Kim; M Kim; M Hagiwara; M Nawrath; K Moelling; D T Curiel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer gene therapy     Volume:  7     ISSN:  0929-1903     ISO Abbreviation:  Cancer Gene Ther.     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-02-29     Completed Date:  2000-02-29     Revised Date:  2010-02-25    
Medline Journal Info:
Nlm Unique ID:  9432230     Medline TA:  Cancer Gene Ther     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  151-9     Citation Subset:  IM    
Affiliation:
Gene Therapy Program, University of Alabama, Birmingham 35294, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / genetics,  immunology*,  pharmacology
COS Cells
Cell Division / drug effects
Doxycycline / pharmacology
Gene Expression Regulation / drug effects
Gene Therapy
Humans
K562 Cells
Leukemia / immunology,  pathology,  therapy*
Proto-Oncogene Proteins c-myb / genetics,  immunology*
Recombinant Proteins / genetics,  immunology
Transfection
Grant Support
ID/Acronym/Agency:
5P30-CA13148-25/CA/NCI NIH HHS; R01 CA68245/CA/NCI NIH HHS; R01 CA72532/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Proto-Oncogene Proteins c-myb; 0/Recombinant Proteins; 564-25-0/Doxycycline

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