Establishment of New Interferon-γ-Resistant Mutant Cells with Dominant Phenotypes

We established interferon-γ-resistant (IGR) cells from a human colon adenocarcinoma cell line, LoVo. Their resistance was extremely high, and the ED50 values of IFN-γ were >105 IU/ml. Interestingly, although IGR-5 cells were still sensitive to the antiproliferative effect of IFN-α, the cells lost responsiveness to the antiviral effects of both IFN-α and γ. Another clone, IGR-53, was unresponsive to both the antiproliferative and antiviral effects of either IFN-α or γ. Furthermore, the IFN-γ-resistant phenotypes of IGR cells were apparently dominant to the parental LoVo cells based on complementation tests. Although IGR-53 cells lack IFN-γ receptors, IGR-5 cells seemed to have functional IFN-γ receptors and processing mechanisms of IFN-γ bound to the receptors. Northern analysis showed that IGR-5 cells responded to IFN-γ and α, but the enhancement of IRF-1 expression by IFN-γ was markedly suppressed.