Uterine cervical carcinogenesis in TGF-alpha transgenic mice

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HPV (human papilloma viruses)-infection appears to be insufficient for carcinogenesis, because most lesions in human cervical squamous epithelium containing high-risk HPVs do not progress to invasive carcinoma. The other genetic alterations in addition to HPV-infection may be also important for cervical carcinogenesis. TGF-alpha overexpression is observed in 10-50% of cervical cancers. In this study, we examined the impact of elevated TGF-alpha in cervical epithelium of TGF-alpha transgenic mice. The incidence of cervical intraepithelial neoplasias (CINs) was 38% (6/16) in TGF-alpha transgenic mice. Invasive carcinoma was not observed. These findings suggest that constitutive expression of TGF-alpha and activation of the epidermal growth factor receptor in epithelium of uterine cervix may play an important role in tumorigenesis in this tissue.