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Differential regulation of different human papilloma virus variants by the POU family transcription factor Brn-3a

Oncogene volume 25, pages 51–60 (2006)Cite this article

Abstract

The Brn-3a POU family transcription factor is overexpressed in human cervical carcinoma biopsies and is able to activate expression of the human papilloma virus type 16 (HPV-16) upstream regulatory region (URR), which drives the expression of the E6 and E7 oncoproteins. Inhibition of Brn-3a expression in human cervical cancer cells inhibits HPV gene expression and reduces cellular growth and anchorage independence in vitro as well as the ability to form tumours in vivo. Here, we show that Brn-3a differentially regulates different HPV-16 variants that have previously been shown to be associated with different risks of progression to cervical carcinoma. In human cervical material, Brn-3a levels correlate directly with HPV E6 levels in individuals infected with a high risk variant of HPV-16, whereas this is not the case for a low-risk variant. Moreover, the URRs of high- and intermediate-risk variants are activated by Brn-3a in transfection assays, whereas the URR of a low-risk variant is not. The change of one or two bases in a low-risk variant URR to their equivalent in a higher-risk URR can render the URR responsive to Brn-3a and vice versa. These results help explain why the specific interplay between viral and cellular factors necessary for the progression to cervical carcinoma only occurs in a minority of those infected with HPV-16.

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Acknowledgements

This work was supported by the Association for International Cancer Research (AICR).

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Authors and Affiliations

  1. Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK

    D Ndisang, D J Faulkes, D Gascoyne, S A Lee, B J Ripley, M Sindos, V Budhram-Mahadeo & D S Latchman

  2. Department of Women's and Children's Health, The Whittington Hospital, Highgate Hill, London, UK

    M Sindos & A Singer

  3. Richard Dimbleby Laboratory of Cancer Virology, GKT School of Medicine, King's College London, St Thomas' Campus, London, UK

    J Cason

  4. Birkbeck, University of London, London, UK

    D S Latchman

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  1. D Ndisang
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  2. D J Faulkes
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Correspondence to D S Latchman.

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Ndisang, D., Faulkes, D., Gascoyne, D. et al. Differential regulation of different human papilloma virus variants by the POU family transcription factor Brn-3a. Oncogene 25, 51–60 (2006). https://doi.org/10.1038/sj.onc.1209006

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