Paclitaxel resistance in cells with reduced beta-tubulin.
Paclitaxel resistance in cells with reduced beta-tubulin.
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发表时间：
2005
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通讯作者：
Yaqing Wang;F. Cabral
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作者：
Yaqing Wang;F. Cabral
我们之前曾报道过对秋碱抗药的中国仓鼠卵巢细胞系的分离，这些细胞系含有α -和β -微管蛋白突变，可以增加微管的组装和稳定性。通过分析一种β -微管蛋白突变体的秋碱敏感回复性，我们发现突变等位基因的丢失或失活代表了最常见的回复性机制。与这种损失相一致的是，在稳定状态下，回复体的微管蛋白减少了35%，没有证据表明存在突变多肽，微管蛋白聚合的程度正常。除了失去对colcolid的抗性外，与野生型细胞相比，逆转录细胞对紫杉醇的抗性增加。这种紫杉醇抗性可以通过转染野生型β -微管蛋白cDNA来抑制，这表明微管蛋白在逆转细胞中的减少是抗性表型的原因。我们认为降低微管蛋白水平可能是紫杉醇耐药的一种新机制。
We previously described the isolation of colcemid resistant Chinese hamster ovary cell lines containing alpha- and beta-tubulin mutations that increase microtubule assembly and stability. By analyzing colcemid sensitive revertants from one of the beta-tubulin mutants, we now find that loss or inactivation of the mutant allele represents the most common mechanism of reversion. Consistent with this loss, the revertants have 35% less tubulin at steady state, no evidence for the presence of a mutant polypeptide, and a normal extent of tubulin polymerization. In addition to the loss of colcemid resistance, the revertant cells exhibit increased resistance to paclitaxel relative to wild-type cells. This paclitaxel resistance can be suppressed by transfecting the revertant cells with a cDNA for wild-type beta-tubulin, indicating that the reduction in tubulin in the revertant cells is responsible for the resistance phenotype. We propose that reducing tubulin levels may represent a novel mechanism of paclitaxel resistance.