Altered expression of ß-tubuin isotypes in breast cancer cells resistant to docetaxel

Kawan Shalli, Iain Brown, Steven Darryll Heys, Andrew Craig Schofield

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

Abstract

Docetaxel is one of the most active drugs used to treat breast cancer. The cellular target of docetaxel is the microtubule, specifically the beta-tubulin subunit, that comprises a series of isotypes and that can modulate function. This study has examined the role of alteration in beta-tubulin isotypes in vitro and has sequenced the beta-tubulin gene to determine if there were mutations, both of which may represent important mechanisms of acquired resistance to docetaxel. Breast cancer cells, MCF-7 (oestrogen-receptor positive) and MDA-MB-231, (oestrogen-receptor negative) were made resistant to docetaxel in vitro. Expression of beta-tubulin isotypes ( class I, II, III, IVa, IVb, and VI) was determined at the RNA and protein level using RT-PCR and western analysis, respectively. DNA sequencing evaluated the beta-tubulin gene. At the mRNA level, class I, II, III, and IVa beta-tubulin mRNA isotypes were over-expressed in docetaxel-resistant MCF-7 cells when compared with the docetaxel-sensitive parental cells. However, class VI beta-tubulin mRNA isotype expression was decreased in resistant cells. In MDA-MB-231 cells, there was a decrease in expression of the class I and class IVa beta-tubulin mRNA. However, there were increased expressions in class II, IVb, and VI beta-tubulin mRNA isotypes in resistant cells. Western analysis has confirmed corresponding increases in beta-tubulin protein levels in MCF- 7 cells. However, in MDA-MB-231 cells, there were decreased protein levels for class II and class III beta-tubulin. This study demonstrates that altered expression of mRNA beta-tubulin isotypes and modulation of beta-tubulin protein levels are associated with acquired docetaxel resistance in breast cancer cells. This allows further understanding and elucidation of mechanisms involved in resistance to docetaxel.

Original languageEnglish
Pages (from-to)1299-1301
Number of pages2
JournalThe FASEB Journal
Volume19
DOIs
Publication statusPublished - Aug 2005

Keywords

  • drug resistance
  • MCF-7 and MDA-MB-231 cells
  • EXPRESSION
  • CHEMOTHERAPY
  • TAXOL
  • MICROTUBULES
  • PREDICTION
  • MUTATIONS
  • CARCINOMA
  • DYNAMICS
  • TAXOTERE

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