Leptomycin B induces apoptosis in cells containing the whole HPV 16 genome

Carol E. Jolly, Lindsey J. Gray, Joanna L. Parish, Sonia Lain, C. Simon Herrington

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    Cervical cancer is a major cause of death in women worldwide and is strongly associated with human papillomavirus (HPV) infection. Integration of HPV is thought to be a key step in malignant progression, and is associated with loss of regulation of the viral E6 and E7 oncogenes. Leptomycin B (LMB), a nuclear export inhibitor, has previously been shown to induce apoptosis in primary keratinocytes transduced with the HPV 16 E7 or E6/E7 genes, but not in normal cells. We show here that LMB can also induce apoptosis in derivatives of the W12 cell line that contain either episomal or integrated HPV 16. Cells transduced with HPV 16 E7 or E6/E7, and the episomal and integrated W12 derivatives showed distinct temporal expression patterns of the apoptotic markers activated caspase-3 and M30. The expression of both markers occurred later in the episomal derivatives than in either transduced cells or W12 derivatives containing integrated HPV. These findings suggest that, although LMB can induce apoptosis in keratinocytes containing episomal or integrated HPV 16, genome status is likely to influence the response of HPV-associated anogenital lesions to LMB treatment.

    Original languageEnglish
    Pages (from-to)649-656
    Number of pages8
    JournalInternational Journal of Oncology
    Volume35
    Issue number3
    DOIs
    Publication statusPublished - Sep 2009

    Keywords

    • human papillomavirus
    • W12 derivatives
    • integration
    • leptomycin B
    • apoptosis
    • HUMAN-PAPILLOMAVIRUS TYPE-16
    • CERVICAL-CARCINOMA
    • GENE-EXPRESSION
    • INTEGRATION
    • DNA
    • E6
    • HUMAN-PAPILLOMAVIRUS-16
    • RESISTANCE
    • CANCER
    • DEATH

    Cite this

    Jolly, C. E., Gray, L. J., Parish, J. L., Lain, S., & Herrington, C. S. (2009). Leptomycin B induces apoptosis in cells containing the whole HPV 16 genome. International Journal of Oncology, 35(3), 649-656. https://doi.org/10.3892/ijo_00000377
    Jolly, Carol E. ; Gray, Lindsey J. ; Parish, Joanna L. ; Lain, Sonia ; Herrington, C. Simon. / Leptomycin B induces apoptosis in cells containing the whole HPV 16 genome. In: International Journal of Oncology. 2009 ; Vol. 35, No. 3. pp. 649-656.
    @article{26f32fa47fd049d8b74ec64b2e4c3dd6,
    title = "Leptomycin B induces apoptosis in cells containing the whole HPV 16 genome",
    abstract = "Cervical cancer is a major cause of death in women worldwide and is strongly associated with human papillomavirus (HPV) infection. Integration of HPV is thought to be a key step in malignant progression, and is associated with loss of regulation of the viral E6 and E7 oncogenes. Leptomycin B (LMB), a nuclear export inhibitor, has previously been shown to induce apoptosis in primary keratinocytes transduced with the HPV 16 E7 or E6/E7 genes, but not in normal cells. We show here that LMB can also induce apoptosis in derivatives of the W12 cell line that contain either episomal or integrated HPV 16. Cells transduced with HPV 16 E7 or E6/E7, and the episomal and integrated W12 derivatives showed distinct temporal expression patterns of the apoptotic markers activated caspase-3 and M30. The expression of both markers occurred later in the episomal derivatives than in either transduced cells or W12 derivatives containing integrated HPV. These findings suggest that, although LMB can induce apoptosis in keratinocytes containing episomal or integrated HPV 16, genome status is likely to influence the response of HPV-associated anogenital lesions to LMB treatment.",
    keywords = "human papillomavirus, W12 derivatives, integration, leptomycin B, apoptosis, HUMAN-PAPILLOMAVIRUS TYPE-16, CERVICAL-CARCINOMA, GENE-EXPRESSION, INTEGRATION, DNA, E6, HUMAN-PAPILLOMAVIRUS-16, RESISTANCE, CANCER, DEATH",
    author = "Jolly, {Carol E.} and Gray, {Lindsey J.} and Parish, {Joanna L.} and Sonia Lain and Herrington, {C. Simon}",
    year = "2009",
    month = "9",
    doi = "10.3892/ijo_00000377",
    language = "English",
    volume = "35",
    pages = "649--656",
    journal = "International Journal of Oncology",
    issn = "1019-6439",
    publisher = "Spandidos Publications",
    number = "3",

    }

    Jolly, CE, Gray, LJ, Parish, JL, Lain, S & Herrington, CS 2009, 'Leptomycin B induces apoptosis in cells containing the whole HPV 16 genome', International Journal of Oncology, vol. 35, no. 3, pp. 649-656. https://doi.org/10.3892/ijo_00000377

    Leptomycin B induces apoptosis in cells containing the whole HPV 16 genome. / Jolly, Carol E.; Gray, Lindsey J.; Parish, Joanna L.; Lain, Sonia; Herrington, C. Simon.

    In: International Journal of Oncology, Vol. 35, No. 3, 09.2009, p. 649-656.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Leptomycin B induces apoptosis in cells containing the whole HPV 16 genome

    AU - Jolly, Carol E.

    AU - Gray, Lindsey J.

    AU - Parish, Joanna L.

    AU - Lain, Sonia

    AU - Herrington, C. Simon

    PY - 2009/9

    Y1 - 2009/9

    N2 - Cervical cancer is a major cause of death in women worldwide and is strongly associated with human papillomavirus (HPV) infection. Integration of HPV is thought to be a key step in malignant progression, and is associated with loss of regulation of the viral E6 and E7 oncogenes. Leptomycin B (LMB), a nuclear export inhibitor, has previously been shown to induce apoptosis in primary keratinocytes transduced with the HPV 16 E7 or E6/E7 genes, but not in normal cells. We show here that LMB can also induce apoptosis in derivatives of the W12 cell line that contain either episomal or integrated HPV 16. Cells transduced with HPV 16 E7 or E6/E7, and the episomal and integrated W12 derivatives showed distinct temporal expression patterns of the apoptotic markers activated caspase-3 and M30. The expression of both markers occurred later in the episomal derivatives than in either transduced cells or W12 derivatives containing integrated HPV. These findings suggest that, although LMB can induce apoptosis in keratinocytes containing episomal or integrated HPV 16, genome status is likely to influence the response of HPV-associated anogenital lesions to LMB treatment.

    AB - Cervical cancer is a major cause of death in women worldwide and is strongly associated with human papillomavirus (HPV) infection. Integration of HPV is thought to be a key step in malignant progression, and is associated with loss of regulation of the viral E6 and E7 oncogenes. Leptomycin B (LMB), a nuclear export inhibitor, has previously been shown to induce apoptosis in primary keratinocytes transduced with the HPV 16 E7 or E6/E7 genes, but not in normal cells. We show here that LMB can also induce apoptosis in derivatives of the W12 cell line that contain either episomal or integrated HPV 16. Cells transduced with HPV 16 E7 or E6/E7, and the episomal and integrated W12 derivatives showed distinct temporal expression patterns of the apoptotic markers activated caspase-3 and M30. The expression of both markers occurred later in the episomal derivatives than in either transduced cells or W12 derivatives containing integrated HPV. These findings suggest that, although LMB can induce apoptosis in keratinocytes containing episomal or integrated HPV 16, genome status is likely to influence the response of HPV-associated anogenital lesions to LMB treatment.

    KW - human papillomavirus

    KW - W12 derivatives

    KW - integration

    KW - leptomycin B

    KW - apoptosis

    KW - HUMAN-PAPILLOMAVIRUS TYPE-16

    KW - CERVICAL-CARCINOMA

    KW - GENE-EXPRESSION

    KW - INTEGRATION

    KW - DNA

    KW - E6

    KW - HUMAN-PAPILLOMAVIRUS-16

    KW - RESISTANCE

    KW - CANCER

    KW - DEATH

    U2 - 10.3892/ijo_00000377

    DO - 10.3892/ijo_00000377

    M3 - Article

    VL - 35

    SP - 649

    EP - 656

    JO - International Journal of Oncology

    JF - International Journal of Oncology

    SN - 1019-6439

    IS - 3

    ER -