| Neuronal-associated microtubule proteins class III beta-tubulin and MAP2c in neuroblastoma: role in resistance to microtubule-targeted drugs. | |
MedLine Citation:
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PMID: 15367708 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 3 ISSN: 1535-7163 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-09-15 Completed Date: 2005-02-09 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1137-46 Citation Subset: IM |
Affiliation:
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Children's Cancer Institute Australia for Medical Research, High Street, P.O. Box 81, Randwick, New South Wales 2031, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Drug Resistance, Neoplasm* Humans 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 Stathmin Tubulin / analysis, genetics, metabolism* Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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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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