Characterization of a gastric tumor cell line defective in MHC class I inducibility by both α‐ and γ‐interferon

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Abstract
α/β and γ type interferons (IFN), act through distinct cell surface receptors and induce transcription of an overlapping sets of genes. MHC class I genes are inducible by both type of interferons. We have analyzed a gastric tumor cell line, AGS, which was completely defective in MHC class I response to interferon‐α and ‐γ. Northern blot analysis demonstrated that the lack of IFN response was related with the absence of up‐regulation of specific HLA class I mRNA. Electrophoretic mobility shift assays in various tumor cell lines after IFN‐α and IFN‐γ treatment showed differential binding of the transcriptional factors to MHC class I regulatory elements. Comparison of k‐B binding activity showed that IFN‐α and IFN‐γ induced opposite changes in NF‐kB binding activity in AGS cells, indicating that the absence of MHC class I response in AGS appears to be independent of k‐B activity. In contrast, there were remarkable differences in the level of transcriptional factor binding to an interferon‐responsive sequence element (IRSE), between AGS and other interferon‐responsive tumor cell lines. This result suggests that the low level of transcriptional factor binding to IRSE in AGS cells was responsible of the lack of induction of MHC class I antigens. In this context, overlapping factors in the signal transduction pathway of both type I and II interferons may be involved in the non‐responsiveness of this gastric carcinoma tumor cell line.