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Impact of tululin binding cofactor C (TBCC) on microtubule mass and dynamics, cell cycle, tumor growth and response to chemotherapy in breast cancer

Abstract : The proper folding pathway of α and β-tubulin into the α/β-tubulin heterodimers involve five Tubulin Binding Cofactors (TBCA to TBCE). TBCC plays a crucial role in the formation of polymerization-competent the α/β-tubulin heterodimers. To evaluate the impact of microtubule mass and dynamics on the phenotype and chemosensitivity of breast cancer cells, we targeted TBCC in human breast adenocarcinoma and developed variants of breast cancer cells with modified content of TBCC. We have shown that the modifications in TBCC expression level influenced tubulin fraction distribution and microtubule dynamics. Cell cycle distribution and the durations of mitosis and S-phase were altered. The proliferation rate in vitro was slightly modified whereas in vivo the TBCC variants presented major differences in tumor growth capacity. Chemosensitivity to antimicrotubule agents (paclitaxel and vinorelbine) as well as to gemcitabine was observed to be dependent on the cell cycle distribution of the TBCC variants. These results underline the essential role of fine tuned regulation of tubulin content in tumor cells and the major impact of dysregulation of tubulin dimer content on tumor cell phenotype, cell cycle progression and response to chemotherapy. A better understanding of how the microtubule cytoskeleton is dysregulated in cancer cells would greatly contribute to a better understanding of tumor cell biology and characterization of resistant phenotypes
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https://tel.archives-ouvertes.fr/tel-00869188
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Rouba Hage-Sleiman. Impact of tululin binding cofactor C (TBCC) on microtubule mass and dynamics, cell cycle, tumor growth and response to chemotherapy in breast cancer. Human health and pathology. Université Claude Bernard - Lyon I, 2010. English. ⟨NNT : 2010LYO10085⟩. ⟨tel-00869188⟩

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