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

• Published in: British journal of cancer 2002-01, Vol.86 (2), p.263-268
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adenoviruses; Alternative splicing; Apoptosis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Cell cycle; Cell Transformation, Neoplastic; Cervical Intraepithelial Neoplasia - genetics; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; Cervix; Cloning; DNA-Binding Proteins - biosynthesis; double prime E7 protein; Drug Resistance; E7 protein; Epidemiology; Epithelium; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Gynecology. Andrology. Obstetrics; Human papillomavirus; Humans; Keratinocytes; Medical research; Medical sciences; Molecular and Cellular Pathology; Molecular Medicine; MYB protein; Neoplasia; Nuclear Proteins - biosynthesis; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - pharmacology; Oncology; Overexpression; p14ARF protein; Papillomaviridae - genetics; Papillomavirus Infections - complications; Plasmids; Promoters; Proteins; R&D; Research & development; Squamous cells; Transcriptional Activation; Tumor Cells, Cultured; Tumor Protein p73; Tumor Suppressor Proteins; Tumor Virus Infections - complications; Tumors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600033

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 p73Δ2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Δ2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium.