Transforming properties of a 15-kDa truncated Ad12 E1A gene product.

A mutant Ad12 E1A region (Ad12 R11E1A) was constructed, which directs the synthesis of only a 15-kDa N-terminal E1A product. When controlled by the SV40 early promoter plus enhancer region (SVR11E1A) this mutant E1A region is capable of immortalizing primary baby rat kidney (BRK) cells, showing that the information essential for immortalization is located in the N-terminal part of region E1A and is shared by the 13 S and 12 S mRNA gene products. This immortalization is thought to be an essential step in the process of oncogenic transformation. Primary BRK cells transformed by SVR11E1A in the presence of Ad12 E1B are nononcogenic. This implies that the E1A region also codes for activities required for oncogenicity. However, in the presence of an activated c-Ha-ras oncogene the SVR11E1A region can oncogenically transform primary BRK cells, showing that the c-Ha-ras oncogene not only can complement for the Ad12 E1B region, but also for the E1A function lost by the R11 deletion.