Characterization of a gastric tumor cell line defective in MHC class I inducibility by both alpha- and gamma-interferon.
Alpha/beta and gamma 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-alpha and gamma. 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-alpha and IFN-gamma treatment showed differential binding of the transcriptional factors to MHC class I regulatory elements. Comparison of kappa-B binding activity showed that IFN-alpha and IFN-gamma induced opposite changes in NF-kappa B binding activity in AGS cells, indicating that the absence of MHC class I response in AGS appears to be independent of kappa-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.
Abril
E
E
Departamento de Análisis Clínicos, Hospital Virgen de las Nieves, Universidad de Granada, Spain.
Mendez
R E
RE
García
A
A
Serrano
A
A
Cabrera
T
T
Garrido
F
F
Ruiz-Cabello
F
F
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015703:Antigens, CD / Q000502:physiology; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007822:Laryngeal Neoplasms / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology*; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D006680:HLA Antigens; D016898:Interferon-alpha; D007371:Interferon-gamma; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor