Since in the hamster tumor system the loss of Ad12 DNA sequences is still compatible with the oncogenic phenotype, the possibility exists that human tumors, though themselves devoid of viral DNA sequences, could have had cells as precursors which originally carried integrated adenoviral DNA sequences.
Interestingly, the concentration of the putative tumour suppressor and co-activator p300 was elevated in cell lines expressing high levels of Ad12-E1A and Ad12-E1B due to an increased half-life.
These findings provide the first in vivo evidence that the expression of the Ad12 E1 region gene induces cartinoid tumors associated with the activation of the nuclear oncogenes N-myc and c-jun.
The transcriptional down-regulation of the major histocompatibility complex (MHC) class I antigens in adenovirus type 12 (Ad12) transformed cells gives them the potential to escape immunosurveillance and to form tumors.
Rhim et al. were first to show that superinfection of Ad12-SV40-infected immortalized human epidermal cells with an RNA tumor virus containing a ras oncogene, such as Ki-MSV, or their treatment with chemical carcinogens, leads to the ability of cells to both grow in anchorage-independent fashion and to form tumors in athymic nude mice.
The Ad12-transformed cells uniformly expressed low levels of class I MHC antigens; these cells produced tumors 200- to 1,000-fold less efficiently in allogeneic adult hamsters than in syngeneic adult hamsters and produced tumors with about the same efficiency in immunoimmature newborns and immunocompetent syngeneic adult hamsters.
Thus, despite the fact that all products required for oncogenic transformation in vitro were derived from the highly oncogenic Ad12, the recombinant virus did not produce tumors in vivo.
The levels of expression of the viral genome in the Balb/c tumor and in the retinoblastoma line were determined by in vitro translation of RNA isolated from these cells and selected with appropriate restriction endonuclease fragments of Ad12 DNA.