PURPOSE: The research of HPV has been severely hampered by the inability to propagate HPVs in culture, particularly those of the mucosotrophic types which produce few virions in vivo. In order to study the regulation of HPV-18 expression in vivo, we constructed transgenic mice and caused cervical neoplasia. MATERIALS AND METHODS: We investigated whether tetradecanoyl phorbol acetate (TPA) increase the transcriptional activity of the URR in the C33A cervical carcinoma cells or not. And we asked whether chronic exposure of female HPV-18 URR E6/E7 transgenic mice to TPA could render the reproductive tract squamous epithelium permissive for HPV neoplasia. RESULTS: It was confirmed by RT-PCR that transgene was specifically expressed in epithelial tissues. TPAupregulated the transcriptional activity of the URR in the C33A cervical carcinoma cells. There were diffuse changes on the squamous epithelium in the cervix of the transgenic mice at fifth month following TPA treatment. CONCLUSION: We established the transgenic mice model which have the ability to reproduce the development of cervical dysplasias. Moreover this animal model will allow preclinical testing of compounds designed to interfere with the actions of the HPV oncogenes or other critical aspects of the cancer phenotype.
Animals ; Cervix Uteri ; Epithelium ; Female ; Human papillomavirus 18 ; Humans ; Mice ; Mice, Transgenic* ; Models, Animal ; Oncogenes ; Phenotype ; Transgenes ; Virion