Down-regulation of MHC class I antigen in insulinoma cells controlled by the R1 element of the H-2 enhancer.
Tumorigenesis in mice of the rat insulin promoter [RIP]-simian virus 40 tumor antigen [SV40 Tag] transgenic lineages, RIP1-Tag2 and RIP1-Tag4, is a process initiated by expression of SV40 Tag in pancreatic beta cells, evolution of islet cell hyperplasia and insulinoma appearance. Analysis of major histocompatibility complex [MHC] class I gene expression during this process revealed a normal level of MHC class I molecules at the surface of pancreatic islet cells of RIP1-Tag4 mice, while hyperplastic islets from the same mice contained cells expressing a normal level and cells expressing a low level of MHC class I antigen. Insulinomas themselves expressed very low levels or no MHC class I gene product. Thus, down-regulation of MHC class I gene appears to accompany tumor progression of SV40 Tag-transformed beta islet cells. MHC class I antigen expression in a series of clonally derived cell lines of beta cell origin from different SV40 Tag-induced insulinomas ranged from quite low to undetectable, although expression was inducible by interferon-gamma. Nuclear run-on and transient transfection analyses indicated that expression of the MHC class I gene in these cells in controlled at the transcriptional level, and that the decreased expression is paralleled by reduced binding of transcription factors to the R1 element of the H-2 enhancer.
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Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Kralli
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Ricciardi
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Knowles
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D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002461:Cell Line, Transformed; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic; D006183:H-2 Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D014162:Transfection; D014407:Tumor Cells, Cultured
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D015500:Chloramphenicol O-Acetyltransferase