Altered TUBB3 expression contributes to the epothilone response of mitotic cells

Elli Narvi, Kaarle Jakkola, S. Winsel, C. Oetken-Lindholm, Pekka Halonen, Lila Kallio, M.J. Kallio (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

21 Citations (Scopus)

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.

Conclusion:

Our results show that the expression of TUBB3 contributes to the cellular response to epothilones, putatively by having an impact on the mt dynamics.
Original languageEnglish
Pages (from-to)82-90
Number of pages9
JournalBritish Journal of Cancer
Volume108
Issue number1
DOIs
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed

Fingerprint

Epothilones
Microtubules
Tubulin
Cell Line
Pharmaceutical Preparations
Cell Proliferation
MCF-7 Cells
Drug Delivery Systems
Fluorescence Microscopy
Mitosis
Lung Neoplasms
Cell Death
Breast Neoplasms

Keywords

  • class III ß-tubulin
  • Epothilones
  • microtubules
  • sagopilone
  • TUBB3

Cite this

Narvi, E., Jakkola, K., Winsel, S., Oetken-Lindholm, C., Halonen, P., Kallio, L., & Kallio, M. J. (2013). Altered TUBB3 expression contributes to the epothilone response of mitotic cells. British Journal of Cancer, 108(1), 82-90. https://doi.org/10.1038/bjc.2012.553
Narvi, Elli ; Jakkola, Kaarle ; Winsel, S. ; Oetken-Lindholm, C. ; Halonen, Pekka ; Kallio, Lila ; Kallio, M.J. / Altered TUBB3 expression contributes to the epothilone response of mitotic cells. In: British Journal of Cancer. 2013 ; Vol. 108, No. 1. pp. 82-90.
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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.Conclusion:Our results show that the expression of TUBB3 contributes to the cellular response to epothilones, putatively by having an impact on the mt dynamics.",
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Narvi, E, Jakkola, K, Winsel, S, Oetken-Lindholm, C, Halonen, P, Kallio, L & Kallio, MJ 2013, 'Altered TUBB3 expression contributes to the epothilone response of mitotic cells', British Journal of Cancer, vol. 108, no. 1, pp. 82-90. https://doi.org/10.1038/bjc.2012.553

Altered TUBB3 expression contributes to the epothilone response of mitotic cells. / Narvi, Elli; Jakkola, Kaarle; Winsel, S.; Oetken-Lindholm, C.; Halonen, Pekka; Kallio, Lila; Kallio, M.J. (Corresponding Author).

In: British Journal of Cancer, Vol. 108, No. 1, 2013, p. 82-90.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Altered TUBB3 expression contributes to the epothilone response of mitotic cells

AU - Narvi, Elli

AU - Jakkola, Kaarle

AU - Winsel, S.

AU - Oetken-Lindholm, C.

AU - Halonen, Pekka

AU - Kallio, Lila

AU - Kallio, M.J.

PY - 2013

Y1 - 2013

N2 - 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.Conclusion:Our results show that the expression of TUBB3 contributes to the cellular response to epothilones, putatively by having an impact on the mt dynamics.

AB - 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.Conclusion:Our results show that the expression of TUBB3 contributes to the cellular response to epothilones, putatively by having an impact on the mt dynamics.

KW - class III ß-tubulin

KW - Epothilones

KW - microtubules

KW - sagopilone

KW - TUBB3

U2 - 10.1038/bjc.2012.553

DO - 10.1038/bjc.2012.553

M3 - Article

VL - 108

SP - 82

EP - 90

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 1

ER -