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Distinct mechanisms of interferon‐gamma and tumor necrosis factor‐alpha action in oncogene‐transformed mouse fibroblasts
Author(s) -
Seliger Barbara,
Killian Marion,
Pfizenmaier Klaus
Publication year - 1988
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240380308
Subject(s) - tumor necrosis factor alpha , interferon gamma , alpha (finance) , oncogene , cancer research , action (physics) , interferon , alpha interferon , necrosis , biology , immunology , medicine , cytokine , pathology , cancer , genetics , physics , cell cycle , construct validity , nursing , quantum mechanics , patient satisfaction
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.