Document Detail


Silencing of tubulin binding cofactor C modifies microtubule dynamics and cell cycle distribution and enhances sensitivity to gemcitabine in breast cancer cells.
MedLine Citation:
PMID:  21216936     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tubulin binding cofactor C (TBCC) is essential for the proper folding of α- and β-tubulins into microtubule polymerizable heterodimers. Because microtubules are considered major targets in the treatment of breast cancer, we investigated the influence of TBCC silencing on tubulin pools, microtubule dynamics, and cell cycle distribution of breast cancer cells by developing a variant MCF7 cells with reduced content of TBCC (MC-). MC- cells displayed decreased content in nonpolymerizable tubulins and increased content of polymerizable/microtubule tubulins when compared with control MP6 cells. Microtubules in MC- cells showed stronger dynamics than those of MP6 cells. MC- cells proliferated faster than MP6 cells and showed an altered cell cycle distribution, with a higher percentage in S-phase of the cell cycle. Consequently, MC- cells presented higher sensitivity to the S-phase-targeting agent gemcitabine than MP6 cells in vitro. Although the complete duration of mitosis was shorter in MC- cells and their microtubule dynamics was enhanced, the percentage of cells in G(2)-M phase was not altered nor was there any difference in sensitivity to antimicrotubule-targeting agents when compared with MP6 cells. Xenografts derived from TBCC variants displayed significantly enhanced tumor growth in vivo and increased sensitivity to gemcitabine in comparison to controls. These results are the first to suggest that proteins involved in the proper folding of cytoskeletal components may have an important influence on the cell cycle distribution, proliferation, and chemosensitivity of tumor cells.
Authors:
Rouba Hage-Sleiman; Stéphanie Herveau; Eva-Laure Matera; Jean-Fabien Laurier; Charles Dumontet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-07
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  10     ISSN:  1538-8514     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-10     Completed Date:  2011-10-14     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  303-12     Citation Subset:  IM    
Affiliation:
INSERM 590, Faculté Rockefeller, 8 avenue Rockefeller, 69008 Lyon, France. rhs08@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimetabolites, Antineoplastic / pharmacology
Breast Neoplasms / physiopathology
Cell Cycle / drug effects,  genetics*
Cell Line, Tumor
Cell Proliferation / drug effects
Cytoplasm / metabolism
Deoxycytidine / analogs & derivatives*,  pharmacology
Female
GTP-Binding Proteins / genetics,  metabolism
Gene Silencing*
Humans
Mice
Mice, SCID
Microtubules / genetics,  metabolism*
Molecular Chaperones / genetics*,  metabolism*
Protein Transport
Tubulin / genetics,  metabolism
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Molecular Chaperones; 0/Tubulin; 0/tubulin-specific chaperone C; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine; EC 3.6.1.-/ARL2 protein, human; EC 3.6.1.-/GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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