In vivo evolution of adenovirus 2-transformed cell virulence associated with altered E1A gene function

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.