Suppression of MHC class I RNA in highly oncogenic cells occurs at the level of transcription initiation

The oncogenic potential of some transformed cell lines has been shown in animal tumor models to be the direct result of MHC class I mRNA suppression. Rodent cells established with the highly oncogenic human adenovirus type 12 exhibit greatly reduced levels of class I Ag compared with cells derived with the nononcogenic adenovirus type 5. By using seven independently derived adenovirus-transformed cell lines, we have investigated the mechanism responsible for down-regulation of class I RNA expression. In all adenovirus 12-transformed cells examined, class I RNA suppression was the result of a block in transcription initiation. Highly oncogenic cell lines derived from a spontaneous melanoma and a chemically induced sarcoma also showed greatly reduced transcription of class I genes. We conclude that suppression of MHC class I RNA in a variety of highly oncogenic cells results largely from a substantial decrease in transcription initiation.