Document Detail

Neuronal-associated microtubule proteins class III beta-tubulin and MAP2c in neuroblastoma: role in resistance to microtubule-targeted drugs.
MedLine Citation:
PMID:  15367708     Owner:  NLM     Status:  MEDLINE    
Advanced stage neuroblastoma has a poor clinical outcome and microtubule-destabilizing agents, such as the Vinca alkaloids, are an important component in the treatment of this childhood cancer. Vinca alkaloids bind to beta-tubulin on the alpha/beta-tubulin heterodimer and disrupt microtubule dynamics, leading to cell death. To date, studies examining the contribution of microtubules and associated proteins to the efficacy of microtubule-destabilizing agents in neuroblastoma have been limited. In this study, BE2-C neuroblastoma cells previously selected for resistance to either vincristine (BE/VCR10) or colchicine (BE/CHCb0.2) were found to display significant decreases in neuronal-specific class III beta-tubulin. Interestingly, vincristine-selected cells exhibited increased levels of polymerized tubulin that were not due to alpha-tubulin and class I, II, or III beta-tubulin mutations. Expression levels of the microtubule-depolymerizing protein stathmin were significantly increased in BE/VCR10 cells. In contrast, levels of MAP2a and MAP2b were relatively unaltered. A marked decrease in the neuronal protein, MAP2c, was identified in the vincristine-selected cells and, to a lesser extent, in the colchicine-selected cells. This is the first report describing specific microtubule alterations in neuroblastoma cells resistant to tubulin-targeted agents. The results indicate a need to identify the factors responsible for resistance to tubulin-targeted agents in neuroblastoma so that improved and novel treatment strategies can be developed for this drug refractory disease.
Sima Don; Nicole M Verrills; Tracy Y E Liaw; Marjorie L M Liu; Murray D Norris; Michelle Haber; Maria Kavallaris
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  3     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-15     Completed Date:  2005-02-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1137-46     Citation Subset:  IM    
Children's Cancer Institute Australia for Medical Research, High Street, P.O. Box 81, Randwick, New South Wales 2031, Australia.
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MeSH Terms
Drug Resistance, Neoplasm*
Microtubule Proteins / analysis,  metabolism
Microtubule-Associated Proteins / analysis,  metabolism*
Microtubules / drug effects*,  genetics,  metabolism
Mutation / genetics
Neuroblastoma / drug therapy*,  metabolism*,  pathology
Neurons / immunology,  metabolism
Paclitaxel / pharmacology
Phosphoproteins / analysis,  metabolism
Protein Isoforms / analysis,  metabolism
Tubulin / analysis,  genetics,  metabolism*
Tumor Cells, Cultured
Reg. No./Substance:
0/MAP2 protein, human; 0/MAP4; 0/Microtubule Proteins; 0/Microtubule-Associated Proteins; 0/Phosphoproteins; 0/Protein Isoforms; 0/STMN1 protein, human; 0/Stathmin; 0/Tubulin; 33069-62-4/Paclitaxel

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