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[摘要]：Numerous works have questioned the pertinence of using beta II- and/or beta III-tubulin expression as markers of prognosis and/or prediction of breast cancer response to chemotherapy containing microtubule-targeting agents. The rationale of such studies was essentially based on microtubule dynamics analysis using purified tubulin in vitro and cancer cell lines. Nonetheless, the significance of beta II- and beta III-tubulin expression in the control of microtubule dynamics in normal mammary epithelium has never been addressed. Here we investigate the expression and the consequences of beta II- and/or beta III-tubulin depletion in interphase microtubule dynamics in non-tumor human mammary epithelial cells. We find that both isoforms contribute to the tubulin isotype composition in primary and immortalized human mammary epithelial cells. Moreover, while beta II-tubulin depletion has limited effects on interphase microtubule behavior, beta III-tubulin depletion causes a strong exclusion of microtubules from lamella and a severe suppression of dynamic instability. These results demonstrate that, while beta II-tubulin is dispensable, beta III-tubulin is required for interphase microtubule dynamics in untransformed mammary epithelial cells. This strongly suggests that beta III-tubulin is an essential regulator of interphase microtubule functions in normal breast epithelium cells. (C) 2011 Elsevier GmbH. All rights reserved. |
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