Université de Lyon, F-69000 Lyon, France.
Eur J Cell Biol. 2011 Oct;90(10):872-8. doi: 10.1016/j.ejcb.2011.05.005. Epub 2011 Aug 4.
Numerous works have questioned the pertinence of using βII- and/or βIII-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 βII- and βIII-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 βII- and/or βIII-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 βII-tubulin depletion has limited effects on interphase microtubule behavior, βIII-tubulin depletion causes a strong exclusion of microtubules from lamella and a severe suppression of dynamic instability. These results demonstrate that, while βII-tubulin is dispensable, βIII-tubulin is required for interphase microtubule dynamics in untransformed mammary epithelial cells. This strongly suggests that βIII-tubulin is an essential regulator of interphase microtubule functions in normal breast epithelium cells.
许多研究质疑使用βII-和/或βIII-微管蛋白表达作为乳腺癌对含有微管靶向药物的化疗反应的预后和/或预测标志物的相关性。这些研究的基本原理主要基于体外使用纯化微管蛋白和癌细胞系进行微管动力学分析。然而，βII-和βIII-微管蛋白表达在正常乳腺上皮细胞中控制微管动力学的意义从未得到解决。在这里，我们研究了βII-和/或βIII-微管蛋白在非肿瘤人乳腺上皮细胞的间期微管动力学中的表达及其缺失的后果。我们发现这两种同工型都有助于原发性和永生化人乳腺上皮细胞中微管蛋白同工型的组成。此外，虽然βII-微管蛋白的缺失对间期微管行为的影响有限，但βIII-微管蛋白的缺失导致微管从薄片中强烈排除，并严重抑制动态不稳定性。这些结果表明，虽然βII-微管蛋白是可有可无的，但βIII-微管蛋白对于未转化的乳腺上皮细胞中的间期微管动力学是必需的。这强烈表明βIII-微管蛋白是正常乳腺上皮细胞中间期微管功能的重要调节因子。
