Human papillomavirus 16 E6 increases the radiosensitivity of p53-mutated cervical cancer cells, associated with up-regulation of aurora A

Hye Jin Shin, Joo Young Kim, Lynne Hampson, Hongryull Pyo, Hye Jung Baek, Stephen A. Roberts, Jolyon H. Hendry, Ian N. Hampson

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Purpose:To examine the effect of the human papillomavirus (HPV) type 16-E6 (HPV 'early' gene) oncoprotein on in vitro radiosensitivity of HPV-negative/p53 mutant C33a cervical cancer cells. Methods and materials:The human cervical cancer cell line C33a was stably transfected with either the HPV16 E6 cDNA cloned into the vector pcDNA™3.0 (C33aE6) or the empty-vector control (C33aV). Radiosensitivity, DNA damage, and cell cycle measurements were made using standard clonogenic assays, immunofluorescent assessment of nuclear histone H2AX phosphorylated on serine-139 (γ-H2AX) foci, and flow cytometry. Western immunoblotting and fluorescence confocal microscopy were used to analyse the changes in cellular proteins. Real-time polymerase chain reaction (PCR) was used to compare levels of aurora A mRNA. Results:Compared to C33aV cells, C33aE6 cells showed enhanced radiation cell killing. This was associated with a large amount of polyploidy which was followed by late cell death in C33aE6 cells. Aurora A was highly expressed in C33aE6 cells at pre- and post-irradiation times compared to C33aV cells. Silencing aurora A resulted in a reduced amount of residual γ-H2AX foci in C33aE6 cells, and diminished the difference in radiosensitivity between the C33aE6 and C33aV cells. Conclusion:Our in vitro results indicate that genetic instability could be augmented in the HPV-infected cancer cells by up-regulation of aurora A, especially against a background of dysfunctional p53. Further studies are needed to examine whether aurora A could be a viable therapeutic target in HPV-related tumours. © 2010 Informa UK, Ltd.
    Original languageEnglish
    Pages (from-to)769-779
    Number of pages10
    JournalInternational Journal of Radiation Biology
    Volume86
    Issue number9
    DOIs
    Publication statusPublished - Sept 2010

    Keywords

    • aurora A
    • cervical cancer
    • Human papillomavirus (HPV) 16 E6
    • p53
    • radiosensitivity

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