TUMORIGENICITY OF ADENOVIRUS-TRANSFORMED RODENT CELLS IS INFLUENCED BY AT LEAST 2 REGIONS OF ADENOVIRUS-TYPE-12 EARLY REGION 1A

Chimeric adenovirus type 5 (Ad5)/Ad12 early region IA (E1A) genes were used to transform primary baby rat kidney cells in cooperation with A d12 E1B, and the resulting cell lines were assayed far tumorigenicity in syngeneic rats. It was found that lines were nontumorigenic when tr ansformed by hybrid E1A genes consisting of the amino-terminal 80 amin o acids from Ad12 including conserved region 1 (CR1), with the remaini ng portion from Ad5. In contrast, cell lines transformed by hybrids co ntaining Ad12 E1A sequences from the amino terminus to the leftmost bo rder of CR3 or beyond were tumorigenic. To extend these results, seque nces spanning CR2 and CR3 of Ad5 E1A were replaced with the homologous regions of Ad12 E1A and additional transformed cell lines were establ ished. These lines were weakly-to-moderately tumorigenic, suggesting t hat Ad12 E1A sequences between CR2 and CR3 may be involved in tumorige nicity but are not the sole factors influencing it. Interestingly, exa mination of an EIA sequence alignment indicated that the region betwee n CR2 and CR3 of Ad12 E1A is also conserved in the corresponding seque nce of simian adenovirus type 7, which, like Ad12, is highly oncogenic . This region is characterized by the presence of a stretch of several alanine residues and is similar to a motif present in a number of pro teins with transcriptional repression activity. The possibility that t his region may influence tumorigenicity by means of a transcriptional regulatory mechanism is discussed.