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.
Seliger
B
B
Clinical Research Group, Max-Planck-Society, University of Goettingen, F.R. Germany.
Pfizenmaier
K
K
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics*; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D009857:Oncogenes / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000235:genetics
D006183:H-2 Antigens; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D007371:Interferon-gamma; D015500:Chloramphenicol O-Acetyltransferase