title: Viral and cellular oncogene expression during progressive malignant transformation of SV40 transformed human fibroblasts.
abstract: In vitro investigation of the multistep neoplastic progression which occurs during transformation of human cells has been hindered by resistance of human cells to both immortalization and tumorigenicity (Mut. Res. 199; 273, 1988). Previously our laboratory established a cell line, HSF4-T12, by transfection of normal human foreskin fibroblasts with the plasmid pSV3-neo which contains the early genes of simian virus 40 (SV40). A multistep progression in karyotypic alterations and transformed phenotype occurred resulting in a neoplastic cell line that was immortal, transformed, and tumorigenic. We have examined changes in the SV40 proteins, large T (T-antigen) and small t (t-antigen) antigens, and in the cellular protein, p53, during progressive transformation of these cells. Total viral protein expression relative to total cellular protein increased following immortalization of HSF4-T12 as did the ratio of T-antigen to t-antigen. Interestingly, no significant change in DNA content accompanied immortalization. However, during the progressive in vitro transformation of HSF4-T12 which occurred primarily post-immortalization, DNA index increased to 1.6 but only small additional increases in T-antigen expression were seen. No consistent or critical role for t-antigen in development of the tumorigenic phenotype was found in this system.
authors.affiliation: Department of Pathology, Northwestern University Medical School/VA Lakeside Medical Center, Chicago, Illinois 60611.
authors.forename: C L
authors.initials: CL
authors.lastname: Goolsby
authors.forename: M
authors.initials: M
authors.lastname: Steiner
authors.forename: J
authors.initials: J
authors.lastname: Nemeth
mesh_terms: D000957:Antigens, Viral, Tumor / Q000235:genetics; D015153:Blotting, Western; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005347:Fibroblasts; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010957:Plasmids; D013539:Simian virus 40 / Q000235:genetics*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000957:Antigens, Viral, Tumor; D009856:Oncogene Proteins, Viral; D016159:Tumor Suppressor Protein p53; D004247:DNA