Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    Expression of AP-1 proteins has been associated with a more aggressive clinical outcome in prostate cancer. However, their role and regulation by upstream kinase pathways in response to ionizing radiation has remained elusive. Here, we show that constitutive AP-1 activity in prostate cancer cells is dependent on the activities of EGF-R and PI3K. While inhibition of EGF-R is associated with suppression of c-Jun expression and proliferation, inhibition of PI3K pathway suppresses expression of several AP-1 subunits and proliferation, and also sensitizes prostate cancer cells to gamma-radiation. The importance of AP-1 as a mediator of proliferation and radiation responses is demonstrated by the findings that the expression of JunD, Fra-1 and Fra-2 siRNAs in prostate cancer cells suppress these cellular responses. Together, the findings show that AP-1 activity in prostate cancer cells mediates EGF-R and PI3K signalling, is essential for their proliferation, and confers protection against radiation-induced cell death. Thus, its inhibition would be a lucrative target for therapy in this widely increasing cancer type.
    Alkuperäiskielienglanti
    LehtiInternational Journal of Oncology
    Vuosikerta35
    Numero5
    Sivut1175-1182
    Sivumäärä8
    ISSN1019-6439
    DOI - pysyväislinkit
    TilaJulkaistu - 2009
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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    @article{9033a528b6e848edbecfddb3050a0469,
    title = "Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells",
    abstract = "Expression of AP-1 proteins has been associated with a more aggressive clinical outcome in prostate cancer. However, their role and regulation by upstream kinase pathways in response to ionizing radiation has remained elusive. Here, we show that constitutive AP-1 activity in prostate cancer cells is dependent on the activities of EGF-R and PI3K. While inhibition of EGF-R is associated with suppression of c-Jun expression and proliferation, inhibition of PI3K pathway suppresses expression of several AP-1 subunits and proliferation, and also sensitizes prostate cancer cells to gamma-radiation. The importance of AP-1 as a mediator of proliferation and radiation responses is demonstrated by the findings that the expression of JunD, Fra-1 and Fra-2 siRNAs in prostate cancer cells suppress these cellular responses. Together, the findings show that AP-1 activity in prostate cancer cells mediates EGF-R and PI3K signalling, is essential for their proliferation, and confers protection against radiation-induced cell death. Thus, its inhibition would be a lucrative target for therapy in this widely increasing cancer type.",
    author = "Risto Kajanne and P{\"a}ivi Miettinen and Mikko Tenhunen and Sirpa Lepp{\"a}",
    year = "2009",
    doi = "10.3892/ijo_00000434",
    language = "English",
    volume = "35",
    pages = "1175--1182",
    journal = "International Journal of Oncology",
    issn = "1019-6439",
    publisher = "DEMETRIOS A./SPANDIDOS ED. & PUB",
    number = "5",

    }

    Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells. / Kajanne, Risto; Miettinen, Päivi; Tenhunen, Mikko; Leppä, Sirpa.

    julkaisussa: International Journal of Oncology, Vuosikerta 35, Nro 5, 2009, s. 1175-1182.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells

    AU - Kajanne, Risto

    AU - Miettinen, Päivi

    AU - Tenhunen, Mikko

    AU - Leppä, Sirpa

    PY - 2009

    Y1 - 2009

    N2 - Expression of AP-1 proteins has been associated with a more aggressive clinical outcome in prostate cancer. However, their role and regulation by upstream kinase pathways in response to ionizing radiation has remained elusive. Here, we show that constitutive AP-1 activity in prostate cancer cells is dependent on the activities of EGF-R and PI3K. While inhibition of EGF-R is associated with suppression of c-Jun expression and proliferation, inhibition of PI3K pathway suppresses expression of several AP-1 subunits and proliferation, and also sensitizes prostate cancer cells to gamma-radiation. The importance of AP-1 as a mediator of proliferation and radiation responses is demonstrated by the findings that the expression of JunD, Fra-1 and Fra-2 siRNAs in prostate cancer cells suppress these cellular responses. Together, the findings show that AP-1 activity in prostate cancer cells mediates EGF-R and PI3K signalling, is essential for their proliferation, and confers protection against radiation-induced cell death. Thus, its inhibition would be a lucrative target for therapy in this widely increasing cancer type.

    AB - Expression of AP-1 proteins has been associated with a more aggressive clinical outcome in prostate cancer. However, their role and regulation by upstream kinase pathways in response to ionizing radiation has remained elusive. Here, we show that constitutive AP-1 activity in prostate cancer cells is dependent on the activities of EGF-R and PI3K. While inhibition of EGF-R is associated with suppression of c-Jun expression and proliferation, inhibition of PI3K pathway suppresses expression of several AP-1 subunits and proliferation, and also sensitizes prostate cancer cells to gamma-radiation. The importance of AP-1 as a mediator of proliferation and radiation responses is demonstrated by the findings that the expression of JunD, Fra-1 and Fra-2 siRNAs in prostate cancer cells suppress these cellular responses. Together, the findings show that AP-1 activity in prostate cancer cells mediates EGF-R and PI3K signalling, is essential for their proliferation, and confers protection against radiation-induced cell death. Thus, its inhibition would be a lucrative target for therapy in this widely increasing cancer type.

    U2 - 10.3892/ijo_00000434

    DO - 10.3892/ijo_00000434

    M3 - Article

    VL - 35

    SP - 1175

    EP - 1182

    JO - International Journal of Oncology

    JF - International Journal of Oncology

    SN - 1019-6439

    IS - 5

    ER -