A highly epothilone B–resistant A549 cell line with mutations in tubulin that confer drug dependence

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A highly epothilone B-resistant A549 cell line with mutations in tubulin that confer drug dependence.

A 95-fold epothilone B (EpoB)-resistant, but not dependent, A549 human lung carcinoma cell line, A549.EpoB40 (EpoB40), has a Gln to Glu mutation at residue 292 that is situated near the M-loop of betaI-tubulin. Further selection of this cell line with higher concentrations of EpoB produced A549.EpoB480 (EpoB480), which is approximately 900-fold resistant to EpoB. This cell line, like EpoB40, ex...

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A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells.

The epothilones are naturally occurring antimitotic drugs that share with the taxanes a similar mechanism of action without apparent structural similarity. Although photoaffinity labeling and electron crystallographic studies have identified the taxane-binding site on beta-tubulin, similar data are not available for epothilones. To identify tubulin residues important for epothilone binding, we ...

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Human mutations that confer paclitaxel resistance.

The involvement of tubulin mutations as a cause of clinical drug resistance has been intensely debated in recent years. In the studies described here, we used transfection to test whether beta1-tubulin mutations and polymorphisms found in cancer patients are able to confer resistance to drugs that target microtubules. Three of four mutations (A185T, A248V, R306C, but not G437S) that we tested c...

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Mutations in beta-tubulin map to domains involved in regulation of microtubule stability in epothilone-resistant cell lines.

The epothilones (Epos) are a group of natural products isolated from the myxobacterium, Sorangium cellulosum. They have a mechanism of action similar to that of Taxol, i.e., they stabilize microtubules and induce the formation of microtubule bundles in cells. Because they are simpler in structure than Taxol and preserve their activity in P-glycoprotein-expressing cells, they are being studied a...

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Mutations in -Tubulin Map to Domains Involved in Regulation of Microtubule Stability in Epothilone- resistant Cell Lines

The epothilones (Epos) are a group of natural products isolated from the myxobacterium, Sorangium cellulosum. They have a mechanism of action similar to that of Taxol, i.e., they stabilize microtubules and induce the formation of microtubule bundles in cells. Because they are simpler in structure than Taxol and preserve their activity in P-glycoprotein-expressing cells, they are being studied a...

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ژورنال

عنوان ژورنال: Molecular Cancer Therapeutics

سال: 2005

ISSN: 1535-7163,1538-8514

DOI: 10.1158/1535-7163.mct-05-0024