Genetic Analysis of in Vitro Progression of Human Papillomavirus-transfected Human Cervical Cells1

The authors have established an in vitro model system which demon strates the progression of the transformed phenotypes of human cervical epithelial cells transfected with human papillomavirus (HPV) type 16 and 18 DNAs. Both viral DNAs exhibit immortalizing potential; however, only HPV 18-immortalized cell lines progress to exhibit anchorage-indepen dent growth and, in a limited number of cases, tumorigenesis. In this paper, the authors have examined the genetic basis for this in vitro pro gression step by step, including immortalization, anchorage-independent growth, and tumorigenicity of the HPV-transfected human cervical epi thelial cells by cell fusion. The results suggest that (a) all three trans formed phenotypes, i.e., immortalization, anchorage-independent growth, and tumorigenesis, in this in vitro cervical carcinogenesis model are a result of recessive changes in genes or processes involved; tin inactivation of p53 and retinoblastoma protein is not sufficient for immortalization of human cervical epithelial cells; (c) HPV expression per se does not account for immortalization of human cervical epithelial cells; (d) immortalization of human cervical epithelial cells initiated by HPV can occur through different processes, although one of them is the most preferred; and in probably only one group of recessive genes appears to be involved in the loss of anchorage-dependent growth for HPV-immortalized human cervi