Document Detail


Transfection of glucosylceramide synthase antisense inhibits mouse melanoma formation.
MedLine Citation:
PMID:  11971858     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MEB4 murine melanoma cells synthesize G(M3) as the major ganglioside. Inhibition of G(M3) synthesis by a specific glucosylceramide synthase inhibitor resulted in reduced tumorigenicity and metastatic potential of these cells. We used a molecular approach--antisense transfection targeting the glucosylceramide synthase gene--to regulate glycosphingolipid synthesis by MEB4 cells and examine the influence on tumor formation. Antisense transfection inhibited the synthesis of the direct product of glucosylceramide synthase, glucosylceramide, and consequently G(M3) ganglioside, by MEB4 cells, reducing the concentration of G(M3) in the transfectants by up to 58%. Although neither morphology nor proliferation kinetics of the cultured cells was affected, the inhibition of glycosphingolipid synthesis and reduction of total ganglioside content caused a striking reduction in melanoma formation in mice. Only 1/60 (2%) of mice injected ID with 10(4) antisense-transfected MA173 cells formed a tumor, compared to 31/60 (52%) of mice receiving MEB4 cells and 7/15 (47%) of mice receiving the MS2 sense-transfected cells (p < 0.001 and p = 0.005, respectively). These findings demonstrate that stable transfection of glucosylceramide synthase antisense reduces cellular glycosphingolipid levels and reduces tumorigenicity, providing further experimental support for an enhancing role of gangliosides in tumor formation.
Authors:
Wen Deng; Ruixiang Li; Michael Guerrera; Yihui Liu; Stephan Ladisch
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Glycobiology     Volume:  12     ISSN:  0959-6658     ISO Abbreviation:  Glycobiology     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-04-24     Completed Date:  2002-10-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  145-52     Citation Subset:  IM    
Affiliation:
Glycobiology Program, Center for Cancer and Transplantation Biology, Children's Research Institute and Department of Pediatrics and Biochemistry/Molecular Biology, George Washington University School of Medicine, Washington, DC 20010, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Cell Division / drug effects
DNA Primers
Gangliosides / metabolism
Glucosyltransferases / genetics*
Humans
Medulloblastoma
Melanoma, Experimental / prevention & control*
Mice
Oligodeoxyribonucleotides, Antisense / administration & dosage,  pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Transfection / methods
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA61010/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Gangliosides; 0/Oligodeoxyribonucleotides, Antisense; EC 2.4.1.-/Glucosyltransferases; EC 2.4.1.80/ceramide glucosyltransferase

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