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 other cytokines. Both IFNalpha and IFNgamma have been shown to exert their effects via a recently discovered signalling pathway by inducing tyrosine phosphorylation of their receptors. Receptors for interferons and other cytokines signal through the action of associated protein tyrosine kinases of the JAK family (Janus kinase) and latent cytoplasmic transcriptional activators from the STAT family (signal transducers and activators of transcription). Here we report a gastric adenocarcinoma cell line, AGS, that is defective in its response to either IFNalpha or IFNgamma. AGS cells display selective alterations only in MHC class I inducibility and not in constitutive MHC class I expression. In nuclear extracts of AGS cells, no binding activity to interferon-responsive elements (GAS/ISRE) was observed. We found that AGS cells showed an extremely low level of STAT1 expression, which may be responsible for the absence of biological response to IFN. Because STAT1-deficient cells are highly sensitive to infection by virus, the absence of these proteins may also contribute to the tumor phenotype, giving the tumor a selective advantage, by inhibiting cell growth suppression mediated by IFN and abetting escape from the T cell antitumor response.
Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Spain.
E
E
Abril
L M
LM
Real
A
A
Serrano
P
P
Jimenez
A
A
García
J
J
Canton
I
I
Trigo
F
F
Garrido
F
F
Ruiz-Cabello
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000235:genetics / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000172:deficiency*; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D015534:Trans-Activators / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D007371:Interferon-gamma