Role of adenovirus types 5 and 12 early region 1b tumor antigens in oncogenic transformation.

Recently we have reported that the difference in oncogenic potential between adenovirus type 5 (Ad5)-and Ad12-transformed cells in athymic nude mice is specified by early region 1b. In order to determine which of the two early region 1b (E1b) tumor antigens is responsible for the observed difference in oncogenicity we have constructed two Ad5/Ad12 hybrid plasmids: one allowing expression of the Ad5 19kD and Ad12 54kD E1b proteins, the other of the Ad5 58kD plus Ad12 19kD E1b polypeptides. Both hybrid plasmids contain the intact E1a regions of both serotypes. The chimeric plasmids were used to transform primary cultures of baby rat kidney cells and the resulting transformed cells were tested for oncogenicity in athymic nude mice. It was found that the degree of oncogenicity is determined by the identity of the large E1b tumor antigen. Studies with cells transformed by an Ad12 region E1 plasmid in which the gene coding for the 19kD tumor antigen was mutated showed that expression of this protein is nevertheless required for manifestations of the oncogenic phenotype of the transformed cell.