| Silencing of tubulin binding cofactor C modifies microtubule dynamics and cell cycle distribution and enhances sensitivity to gemcitabine in breast cancer cells. | |
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MedLine Citation:
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PMID: 21216936 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Tubulin Binding cofactor C (TBCC) is essential for the proper folding of α and β tubulins into microtubule polymerizable heterodimers. Since 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 to 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 G2-M phase was not altered nor was there any difference in sensitivity to antimicrotubule targeting agents when compared to MP6 cells. Xenografts derived from TBCC variants displayed significantly enhanced tumor growth in vivo as well as 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. |
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Authors:
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Rouba Hage-Sleiman; Stéphanie Herveau; Eva-Laure Matera; Jean-Fabien Laurier; Charles Dumontet |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-7 |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: - ISSN: 1538-8514 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Faculté de Médecine Rockefeller, Inserm U590-Laboratoire de Cytologie Analytique. |
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