UNRESPONSIVENESS TO INTERFERON ASSOCIATED WITH STAT1 PROTEIN-DEFICIENCY IN A GASTRIC ADENOCARCINOMA CELL-LINE

HC class I expression can be up-regulated by interferons (IFN) and oth er cytokines. Both IFN alpha and IFN gamma have been shown to exert th eir effects via a recently discovered signalling pathway by inducing t yrosine phosphorylation of their receptors. Receptors for interferons and other cytokines signal through the action of associated protein ty rosine kinases of the JAK family (Janus kinase) and latent cytoplasmic transcriptional activators from the STAT family (signal transducers a nd activators of transcription). Here we report a gastric adenocarcino ma cell line, AGS, that is: defective in its response to either IFN al pha or IFN gamma. AGS cells display selective alterations only in MHC class I inducibility and not in constitutive MHC class I expression. I n nuclear extracts of AGS cells, no binding activity to interferon-res ponsive elements (GAS/ISRE) was observed. We found that AGS cells show ed an extremely low level of STAT1 expression, which may be responsibl e for the absence of biological response to IFN. Because STAT1-deficie nt cells are highly sensitive to infection by virus, the absence of th ese proteins may also contribute to the tumor phenotype, giving the tu mor a selective advantage, by inhibiting cell growth suppression media ted by IFN and abetting escape from the T cell antitumor response.