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E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia

  1. Author:
    Brooks, L. A.
    Sullivan, A.
    O'Nions, J.
    Bell, A.
    Dunne, B.
    Tidy, J. A.
    Evans, D. J.
    Osin, P.
    Vousden, K. H.
    Gusterson, B.
    Farrell, P. J.
    Storey, A.
    Gasco, M.
    Sakai, T.
    Crook, T.

  2. Author Address

    St Marys Hosp, Sch Med, Ludwig Inst Canc Res, Norfolk Pl, London W2 1PG, England. St Marys Hosp, Sch Med, Ludwig Inst Canc Res, London W2 1PG, England. Univ Glasgow, Western Infirm, Dept Pathol, Glasgow G11 6NT, Lanark, Scotland. Univ Sheffield, No Gen Hosp, Dept Gynaecol Oncol, Sheffield S5 7AU, S Yorkshire, England. St Marys Hosp, Sch Med, Dept Histopathol, London W2, England. Univ Coll London Hosp, Dept Pathol, London WC1, England. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. St Bartholomews & Royal London Sch Med & Dent, Ctr Cutaneous Res, London E1 2AT, England. Azienda Osped S Croce & Carle, UO Oncol Med, I-12100 Cuneo, Italy. Kyoto Prefectural Univ Med, Dept Prevent Med, Kamigyo Ku, Kyoto 6028566, Japan. Crook T St Marys Hosp, Sch Med, Ludwig Inst Canc Res, Norfolk Pl, London W2 1PG, England.
    1. Year: 2002
  2. Journal: British Journal of Cancer
    1. 86
    2. 2
    3. Pages: 263-268
  4. Type of Article: Article
  1. Abstract:

    In common with other E2F1 responsive genes such as p14(ARF) and B-(myb), the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Delta2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Delta2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium. (C) 2002 The Cancer Research Campaign.

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