title: Altered TUBB3 expression contributes to the epothilone response of mitotic cells.
abstract: BACKGROUND
  Epothilones are a novel group of microtubule (mt) targeting cancer drugs that bind to the β-subunit of the αβ-tubulin dimer. Epothilones inhibit cell proliferation and induce cell death by interfering with the normal mt function. In this study, we examined the consequences of altered expression of human β-tubulin isotypes in terms of the epothilone drug response in human lung and breast cancer cell lines.
  
  
  METHODS
  The β-tubulin isotypes TUBB2A-C, TUBB3 and TUBB were silenced or overexpressed in A549, A549EpoB40 and MCF7 cell lines in the presence or absence of epothilones. The drug effects on cell proliferation, mitosis and mt dynamics were determined using live cell microscopy and immunofluorescence assays.
  
  
  RESULTS
  Loss of TUBB3 enhanced the action of epothilones. TUBB3 knockdown increased the severity of drug-induced mitotic defects and resulted in stabilisation of the mt dynamics in cells. Moreover, exogenous expression of TUBB3 in the epothilone resistant cell line conferred the response to drug treatments. In contrast, reduced levels of TUBB2A-C or TUBB had not apparent effect on the cells' response to epothilones.
  
  
  CONCLUSIONS
  Our results show that the expression of TUBB3 contributes to the cellular response to epothilones, putatively by having an impact on the mt dynamics.
authors: Centre of Biotechnology, University of Turku, 20520 Turku, Finland.
authors: E
authors: E
authors: Narvi
authors: K
authors: K
authors: Jaakkola
authors: S
authors: S
authors: Winsel
authors: C
authors: C
authors: Oetken-Lindholm
authors: P
authors: P
authors: Halonen
authors: L
authors: L
authors: Kallio
authors: M J
authors: MJ
authors: Kallio
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D034261:Epothilones / Q000494:pharmacology*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D061986:MCF-7 Cells; D008938:Mitosis / Q000187:drug effects*; D009369:Neoplasms; D008941:Spindle Apparatus / Q000187:drug effects; D014162:Transfection; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C498585:TUBB3 protein, human; D014404:Tubulin; D050257:Tubulin Modulators