Accompanying protein alterations in malignant cells with a microtubule-polymerizing drug-resistance phenotype and a primary resistance mechanism 1 1Abbreviations: MTs, microtubules; MAPs, microtubule-associated proteins; MAP4, microtubule-associated protein-4; PTX, paclitaxel; EPOA, epothilone A; EPOB, epothilone B; EPOA-R, epothilone A-resistant; COL, colchicine; VCR, vincristine; and VBL, vinblastine.

Utilizing parental and drug-resistant ovarian carcinoma cell lines that have acquired point mutations in β-tubulin and p53, we studied the level of expression and modification of proteins involved in apoptosis and MT integrity

Marianne S. Poruchynsky

2002

Scholarcy highlights

  • Microtubules are cytoskeletal components whose structural integrity is mandatory for the execution of many basic cell functions
  • Utilizing parental and drug-resistant ovarian carcinoma cell lines that have acquired point mutations in β-tubulin and p53, we studied the level of expression and modification of proteins involved in apoptosis and MT integrity
  • We demonstrated phosphorylation of pro-survival Bcl-xL in an epothilone-A resistant cell line, correlating it with drug sensitivity to tubulin-active compounds
  • Phosphorylation of MT-associated protein-4 correlated with sensitivity to tubulin-binding drugs and with a dissociation from MTs
  • We propose that the tubulin mutations, which result in a compromised paclitaxel:tubulin or epothilone:tubulin interaction and paclitaxel or epothilone resistance, indirectly inhibit downstream events that lead to cell death, and this, in turn, may contribute to the drug-resistance phenotype

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