Establishment of new interferon-gamma-resistant mutant cells with dominant phenotypes.
We established interferon-gamma-resistant (IGR) cells from a human colon adenocarcinoma cell line, LoVo. Their resistance was extremely high, and the ED50 values of IFN-gamma were > 10(5) IU/ml. Interestingly, although IGR-5 cells were still sensitive to the antiproliferative effect of IFN-alpha, the cells lost responsiveness to the antiviral effects of both IFN-alpha and gamma. Another clone, IGR-53, was unresponsive to both the antiproliferative and antiviral effects of either IFN-alpha or gamma. Furthermore, the IFN-gamma-resistant phenotypes of IGR cells were apparently dominant to the parental LoVo cells based on complementation tests. Although IGR-53 cells lack IFN-gamma receptors, IGR-5 cells seemed to have functional IFN-gamma receptors and processing mechanisms of IFN-gamma bound to the receptors. Northern analysis showed that IGR-5 cells responded to IFN-gamma and alpha, but the enhancement of IRF-1 expression by IFN-gamma was markedly suppressed.
Ohta
T
T
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Ando
O
O
Kurimoto
M
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004351:Drug Resistance; D006801:Humans; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D017471:Receptors, Interferon / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000302:isolation & purification
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; D010750:Phosphoproteins; D017471:Receptors, Interferon; D007371:Interferon-gamma