[The role of papillomaviruses in the etiology of cervix cancer].
During the past fifteen years strong evidence has accumulated that particular types of human papilloma viruses are involved in the aetiology of cervical cancer. Early reports suggested that women with cytological signs of papilloma virus infection have a significantly higher risk to develop cervical cancer. Recent studies with sensitive detection methods for viral nucleic acids, however, demonstrated that latent papilloma virus infections are widespread and that only a minor part of infected people will suffer from epithelial lesions that may progress to invasive cancer. The infection per se is apparently not sufficient to induce the malignant phenotype in genital keratinocytes. Detailed molecular analysis of cervical cancer cells revealed that the DNA of the cancer associated papilloma viruses is usually integrated into the cellular genome of the carcinoma cells. Only two viral genes (E6 and E7) are always preserved in a functional active state. The expression of these two genes is deregulated since physiological control mechanisms for viral gene expression are eliminated by the integration process. Artificial introduction of the E6-E7 genes into genital keratinocytes leads to unlimited growth of these cells in tissue culture but does not convert them into the malignant state. Keratinocytes that express the E6-E7 genes resemble in some aspects cells found in premalignant lesions, e.g. the cervical intraepithelial neoplasia (CIN). Thus, the deregulated expression of the papilloma virus E6-E7 genes appears not to be sufficient to evoke cancer. Additional not yet characterized factors must cooperate with the viral E6-E7 genes to transform keratinocytes into the full malignant phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
von Knebel Doeberitz
M
M
Institut für Virusforschung/ATV, Heidelberg.
D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002584:Cervix Uteri / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D014412:Tumor Virus Infections / Q000473:pathology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
Die Rolle der Papillomviren in der Atiologie des Zervixkarzinoms.