INDUCTION OF DIFFERENTIATION-REGULATED TRANSCRIPTION FACTOR OCT-6 SPECIFICALLY ACCOMPANIES MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I DOWN-REGULATION BY E1A OF ONCOGENIC ADENOVIRUS-TYPE-12

The E1A genes from adenovirus (Ad) types 5 and 12 share the capacity t o cooperate with a second oncogene to transform primary rodent cells i n vitro. However, only Ad12-transformed cells are oncogenic in immunoc ompetent rodents, an event that requires conserved region 3 (CR3) of E 1A to be intact. Ad12-induced tumorigenicity correlates with the E1A-C R3-dependent down-modulation of MHC class I transcription, contributin g to escape from CTL-mediated immune surveillance. Expression of MHC c lass I antigens is also lacking in undifferentiated embryonal carcinom a cells. In these cells, MHC class I expression increases during diffe rentiation in a process possibly involving octamer-binding proteins. W e found that both nononcogenic and oncogenic Ad-transformed cells cont ained the ubiquitously expressed factor Oct-1. In contrast, only oncog enic Ad12-transformed cells that are derived from primary tell culture s expressed an additional octamer-binding factor, which we identified as Oct-6. The induction of Oct-6 expression was at the RNA level and w as found to require an intact CR3 domain in Ad12 E1A. Like MHC class I expression, Oct-6 expression was not affected in already established cell lines expressing Ad12 EIA. The presence of Oct-6 in Ad12-transfor med cells correlated with an increase in octamer-dependent transcripti on of a reporter gene, relative to Ad5-transformed cells. These result s reveal a novel function for the Ad12-E1A oncoprotein and demonstrate an inverse correlation between the expression of Oct-6 and MHC class I genes in cells oncogenically transformed by Ad12.