Inhibition of Interferon-<IMG SRC="/math/gamma.gif" ALT="{gamma}" BORDER="0"> Antiviral and Antiproliferative Activities by ras Oncogene Expression

In this study, we evaluated the effect of ras oncogene activation on cell response to interferons (LFNs). For this purpose, we treated NIH 3T3 murine fibroblasts transfonned by transfection with K-, Ha-, or N-ras oncogenes, either mutated or amplified, for 24 hours with IFN-γ or IFN-α. We evaluated cell response by measuring virus replication, [3H]thymidine incorporation, 2′,5′- oligoadenylate synthetase activation, and class I antigen induction. Transformed cells were much less responsive to IFN-γ antiviral and antiproliferative activities than normal NIH 3T3 cells. Similarly, the induction of 2′,5′-oligoadenylate synthetase following IFN-γ treatment was completely depressed in transformed cells. Only class I antigens, measured at the cell surface and mRNA levels, appeared partially inducible by IFN-γ in ras-transformed cells. When the same cell lines were treated with IFN-α, we observed full response. Because both normal and ras-transformed NIH 3T3 cells were able to bind [125I]IFN-γ with comparable K<inf>d</inf> values (8.3 × 10−11 M</it> vs. 3 × 10−11 M</it>, respectively), these findings suggest that ras oncogenes may differentially impair IFN-γactivities by affecting activation of IFN-inducible genes downstream from the receptor binding event.