title: Inhibition of interferon-gamma antiviral and antiproliferative activities by ras oncogene expression.
abstract: In this study, we evaluated the effect of ras oncogene activation on cell response to interferons (IFNs). For this purpose, we treated NIH 3T3 murine fibroblasts transformed by transfection with K-, Ha-, or N-ras oncogenes, either mutated or amplified, for 24 hours with IFN-gamma or IFN-alpha. 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-gamma antiviral and antiproliferative activities than normal NIH 3T3 cells. Similarly, the induction of 2',5'-oligoadenylate synthetase following IFN-gamma treatment was completely depressed in transformed cells. Only class I antigens, measured at the cell surface and mRNA levels, appeared partially inducible by IFN-gamma in ras-transformed cells. When the same cell lines were treated with IFN-alpha, we observed full response. Because both normal and ras-transformed NIH 3T3 cells were able to bind [125I]IFN-gamma with comparable Kd values (8.3 X 10(-11) M vs. 3 X 10(-11) M, respectively), these findings suggest that ras oncogenes may differentially impair IFN-gamma activities by affecting activation of IFN-inducible genes downstream from the receptor binding event.
authors.affiliation: Institute of Microbiology, University of Turin Medical School, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gariglio
authors.forename: G
authors.initials: G
authors.lastname: Gribaudo
authors.forename: A
authors.initials: A
authors.lastname: Franco
authors.forename: M A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: G
authors.initials: G
authors.lastname: Cavallo
authors.forename: S
authors.initials: S
authors.lastname: Landolfo
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005786:Gene Expression Regulation; D011905:Genes, ras; D006131:Growth Inhibitors; D006183:H-2 Antigens / Q000235:genetics; D007370:Interferon Type I / Q000037:antagonists & inhibitors; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D014762:Viral Interference
chemical_list: D006131:Growth Inhibitors; D006183:H-2 Antigens; D007370:Interferon Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase