The use of a human papillomavirus 18 promoter for tissue-specific expression in cervical carcinoma cells

Mandy S Y Lung, Wendy M. Mak, Vincent Murray*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    The use of tissue-specific promoter elements in the treatment of cervical cancer has been explored in this paper. The P105 promoter of human papillomavirus 18 (HPV18) was utilised to direct tissue-specific expression in a number of cell types. Expression was examined in three cervical carcinoma cell lines: HeLa (HPV18 positive), SiHa (HPV16 positive), and C33A cells (HPV negative); the epithelial cell line, H1299; and the foetal fibroblast cell line, MRC5, utilising a luciferase expression vector. Expression was highest in the cervical cell lines by a factor of at least 80. The effect of a number of mutations in the P105 promoter on expression levels was examined. Three deletion constructs of the long control region (LCR) were investigated: an 800 bp fragment (LCR800), a 400 bp fragment (LCR400), and a 200 bp fragment (LCR200), as well as the full length product LCR of HPV18 (LCR1000). The LCR800 construct of the HPV18 P105 promoter had the highest level of expression in the cervical cell lines and was also highest in the HPV18-positive HeLa cell line. Site-directed mutagenesis was then employed on the LCR800 construct to create four further constructs that each had inactivating mutations in one of the four E2 binding sites (E2BSs). Overall, this study indicated that the LCR800 construct of the HPV18 P105 promoter could be utilised as a tissuerestricted promoter in cervical cancer cells.

    Original languageEnglish
    Pages (from-to)477-492
    Number of pages16
    JournalCellular and Molecular Biology Letters
    Volume16
    Issue number3
    DOIs
    Publication statusPublished - 2011

    Keywords

    • Cervical cancer
    • E2-binding site
    • Gene therapy
    • HPV18
    • Long control region

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