Rat cells transformed by the highly oncogenic adenovirus 12 lack at least two cellular proteins which are present in cells transformed by the non-oncogenic adenovirus 5 and in untransformed cells. One protein has been identified as the heavy chain of the rat class I major histocompatibility complex. This finding may explain the difference in oncogenicity between adenoviral species.

The distribution and stability of the cellular tumor antigen p53 were studied in baby rat kidney cells transformed by region El sequences of nononcogenic adenovirus (Ad) type 5 (Ad5) or oncogenic type 12 (Adl2). In transformed cells expressing the large ElB T antigen of AdS, p53 was associated with this T antigen. The complexed proteins were concentrated in a cytoplasmic body, which has been shown to consist of a cluster of 8-nm filaments (A. Zantema et al., Virology 142:44-58, 1985). In transformed cells expressing the EIB region of Adl2, however, no association between the viral large T antigen and p53 was detectable. In the latter case, both proteins were found almost exclusively in the nucleus. The stability of p53 in both Ad5-and Adl2-transformed cells was increased relative to that in primary cells or cells immortalized by the ElA region only. Thus, the increased stability of p53 in Ad-transformed cells is not caused by association with a viral T antigen, but it correlates with expression of E1B and with morphological transformation.

No abstract

Expression of class I MHC transplantation antigens has been shown to be reduced in baby rat kidney (BRK) cells transformed by highly oncogenic adenovirus type 12 (Ad12), as compared with untransformed cells and cells transformed by non‐oncogenic Ad5. Here we show that this reduction of class I expression also occurs in a variety of other primary cell cultures transformed by Ad12, and that reduction of class I gene expression occurs for all class I loci. Transfection of Ad5E1 into class I‐negative Ad12‐transformed BRK cells leads to complete restoration of class I expression. Introduction of Ad12E1 into most class I‐positive established cell lines does not result in suppression of class I expression. However, transfection of the Ad12E1A region into a class I‐positive cell line which was immortalized by a mutant Ad12E1A region resulted in suppression of class I gene expression, implying that the suppression of class I activity in Ad12‐transformed cells is due to an active switching‐off process.

Expression of the class I transplantation antigens of the major histocompatibility complex (MHC) is suppressed in cells transformed by the oncogenic human adenovirus 12 (Ad12). This suppression of class I antigen expression, which contributes to the tumorigenic phenotype of the transformed cells, has also been observed in some naturally occurring cancers. In the present study, the rate of transcription initiation of class I genes was measured by a nuclear run-on assay in Ad5- and Ad12-transformed cells of three different types. The rate of transcription was the same in all three. The stability of the class I messenger RNA was also examined and found to be the same in all three cell types. The results indicate that in Ad12-transformed cells the suppression is caused by an inhibition of the post-transcriptional processing of class I MHC messenger RNA in the nucleus.