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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Post-transcriptional downregulation of MHC class I expression in oncogene-transformed cells is reverted by IFN-gamma and TNF-alpha.

Transformation of murine NIH3T3 fibroblasts with retroviral vectors carrying the mos, myc and the Ha-ras oncogene, respectively, was associated with a strong reduction of H2 antigen expression in the cell membrane. Analysis of H-2K and beta 2-microglobulin promoter-driven CAT activity in these oncogenic transformants and normal NIH3T3 fibroblasts revealed unchanged promoter activity, suggesting post-transcriptional control of MHC class I expression by these oncogenes. Treatment with IFN-gamma and TNF-alpha caused 2- to 3-fold enhancement of H-2K and beta 2-microglobulin promoter activity, as well as a normalization (TNF-alpha treatment) or enhancement (IFN-gamma treatment) of H2 membrane expression. These data suggest that IFN-gamma as well as TNF-alpha can counteract downregulation of H-2 genes by interference with an oncogene-induced, post-transcriptional block as well as by a direct enhancement of H-2 gene transcription.[1]


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