title: In vivo evolution of adenovirus 2-transformed cell virulence associated with altered E1A gene function.
abstract: Neoplastic cell populations may evolve to a state of higher virulence in immunocompetent hosts. Transforming gene involvement in this process of tumor progression was evaluated using adenovirus type 2 (Ad2)-transformed hamster cells that are highly susceptible to destruction by natural killer cells and activated macrophages, due to Ad E1A gene function, and are nontumorigenic in immunocompetent animals. Cells selected for increased tumorigenicity retained parental cell patterns of viral gene integration and methylation and expressed Ad2 E1A proteins but exhibited altered E1A function evidenced by decreased susceptibility to killer cell-mediated lysis and inability to support E1A(-) mutant virus replication. The data suggest that an interruption in cellular pathways of E1A expression may result in increased transformed cell virulence.
authors.affiliation: Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
authors.forename: J L
authors.initials: JL
authors.lastname: Cook
authors.forename: A M
authors.initials: AM
authors.lastname: Lewis
authors.forename: T
authors.initials: T
authors.lastname: Klimkait
authors.forename: B
authors.initials: B
authors.lastname: Knust
authors.forename: W
authors.initials: W
authors.lastname: Doerfler
authors.forename: T A
authors.initials: TA
authors.lastname: Walker
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000472:pathogenicity*; D017456:Adenovirus Early Proteins; D000818:Animals; D002472:Cell Transformation, Viral; D006224:Cricetinae; D005786:Gene Expression Regulation; D007121:Immunocompetence; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008647:Mesocricetus / Q000276:immunology; D051379:Mice; D008819:Mice, Nude / Q000276:immunology; D009374:Neoplasms, Experimental / Q000209:etiology / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000502:physiology*; D014774:Virulence
chemical_list: D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral