The long-range goal of our research is to understand the process by which simian virus 40 acts to transform cells in culture and to cause tumors in animals. We propose to examine the roles that SV40-encoded proteins play in transformation and oncogenicity. By understanding the mechanism of SV40 oncogenesis, we hope to move closer to an understanding of human cancer.
Our specific aims are to use an SV40 early region deletion mutant that we have isolated to discover the SV40 functions that are involved in cellular transformation and oncogenesis. The mutant, F8dl, lacks over 60% of the coding sequences for the SV40 large tumor antigen and yet this mutant still can transform and cause tumors. We propose to answer the following questions: 1) Does the F8dl-encoded T antigen bind to specific sites on cellular DNA? 2) Does the F8dl-encoded T antigen bind to specific sequences on cellular chromatin? 3) Are interactions of T antigen within cellular nuclei important for transformation and if so, how does T antigen act within the nucleus to transform?
