Distinct mechanisms of interferon-gamma and tumor necrosis factor-alpha action in oncogene-transformed mouse fibroblasts.
The potential mechanisms of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha action on tumor cells have been investigated in a model of mouse fibroblasts transformed by distinct retroviral vectors carrying the v-mos, c-myc, and v-Ha-ras oncogene, respectively. Treatment with both cytokines not only caused growth inhibition of v-mos- and c-myc-transformants, but also a reversion of transformation-induced suppression of major histocompatibility complex (MHC) class I antigen expression in all transformed cell lines. The phenotypical reversion of transformants was preceded by a selective modulation of LTR-controlled oncogene expression. TNF-alpha primarily affected stability of oncogene-specific RNAs without influencing the activity of retroviral promoters. In contrast, IFN-gamma was effective at the transcriptional level, apparently due to inhibition of LTR activity as revealed from reduced CAT activity in IFN-gamma-treated LTR-CAT transformants. This IFN-gamma-mediated down-regulation of retroviral promoter activity seemed to be selective for Moloney-virus-derived promoters, since the activity of other viral and cellular promoters was not suppressed by IFN-gamma.
Seliger
B
B
Max-Planck-Society, Medical Clinic of the University of Göttingen, Federal Republic of Germany.
Killian
M
M
Pfizenmaier
K
K
D000818:Animals; D002472:Cell Transformation, Viral / Q000187:drug effects; D005347:Fibroblasts; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000502:physiology*; D009857:Oncogenes; D010641:Phenotype; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma