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

J Immunogenet. Aug-Oct 1989;16(4-5):315-20. doi: 10.1111/j.1744-313x.1989.tb00477.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic / genetics*
  • Chloramphenicol O-Acetyltransferase / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • H-2 Antigens / biosynthesis
  • H-2 Antigens / genetics*
  • Interferon-gamma / physiology*
  • Mice
  • Oncogenes / physiology*
  • Promoter Regions, Genetic / genetics
  • RNA Processing, Post-Transcriptional
  • Tumor Necrosis Factor-alpha / physiology*
  • beta 2-Microglobulin / genetics

Substances

  • H-2 Antigens
  • Tumor Necrosis Factor-alpha
  • beta 2-Microglobulin
  • Interferon-gamma
  • Chloramphenicol O-Acetyltransferase