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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    author = "Elli Narvi and Kaarle Jakkola and S. Winsel and C. Oetken-Lindholm and Pekka Halonen and Lila Kallio and M.J. Kallio",
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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 -