Resistance to microtubule-stabilizing drugs involves two events: beta-tubulin mutation in one allele followed by loss of the second allele.

ABSTRACT: Resistance to Taxol (paclitaxel) or the epothilones (Epo) occurs via the acquisition of point mutations in beta-tubulin residues important for drug-tubulin binding. We have isolated four drug-resistant clones selected with Taxol or Epo A, which harbor distinct beta-tubulin mutations. During the development of a stable drug-resistant phenotype, early clones expressing both wild-type (wt) and mutant beta-tubulin sequences exhibited a 10-fold drug resistance, while more advanced clones expressing only the mutant beta-tubulin sequence exhibited 30 to 50-fold drug resistance. The drug-sensitive parental 1A9 ovarian carcinoma cell line and the drug resistant clones (1A9-A8, 1A9-PTX10 and 1A9-PTX22) were evaluated for loss of heterozygosity (LOH) for beta-tubulin (6p25) by single nucleotide polym

SUBMITTER: Wang Y 

PROVIDER: S-EPMC1861826 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature