Transforming Mechanisms of Simian Virus 40

Major effort in this laboratory is directed toward elucidating the mechanisms utilized by the oncogenic DNA virus simian virus 40 (SV40) to alter cell growth properties and to induce tumors. The virus encodes a multifunctional protein, the large tumor (T) antigen, that is sufficient to convert cells in culture to a transformed phenotype and to induce progressive tumors in immunocompromised and transgenic animals. The SV40 oncogene product is unique. Unlike many other oncogene products that must act cooperatively to fully transform cells, the T antigen alone can convert primary cells to tumorigenic cells. Genetic analysis and molecular techniques are used to dissect the transformation pathways used by T antigen and to relate specific parameters of the transformed cell phenotype to known functions of the protein. Particular attention is paid to the ability of T antigen to bind to and inactivate specific functions of the tumor suppressor or growth control proteins Rb, p53, and 300/p400 as well as its ability to transactivate cell cycle and riosomal RNA genes. An active component of the research involves investigating the role(s) of T antigen activities in generating tumors in specific tissues of transgenic mice bearing portions of the T antigen coding sequence under control of tissue specific transcriptional control regions. These types of investigations provide insight into mechanisms of cell growth control and induction and progression of tumors.