Recent studies have suggested a correlation between increased expression of specific beta-tubulin isotypes and paclitaxel resistance in drug-selected cell lines. In an attempt to establish a causal link, we have transfected Chinese hamster ovary cells with cDNAs encoding epitope-tagged class I, II, and IVb beta-tubulins, as well as a class I beta-tubulin with a mutation previously characterized in a paclitaxel resistant mutant. To eliminate possible toxicity that might be associated with overexpression of non-native tubulin, each of the cDNAs was placed under the control of a tetracycline regulated promoter. All transfected cDNAs produced assembly competent tubulin whose synthesis could be turned off or on by the presence or absence of tetracycline. Production of betaI, betaII, or betaIVb tubulin had no effect on the sensitivity of the cells to paclitaxel, but production of the mutant betaI-tubulin conferred clear resistance to the drug. We conclude from these experiments that simple overexpression of class I, II, or IVb isoforms of beta-tubulin is insufficient to confer resistance to paclitaxel.
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