Transfection of fibroblasts with activated c-myc confers resistance to antigrowth effects of interferon.
The Go/G1 to S transition in growth factor-stimulated Balb/c 3T3 fibroblasts is efficiently blocked by interferons (IFNs). In the present communication we studied whether deregulated expression of exogenously introduced c-myc changes the growth sensitivity to type I IFNs (alpha + beta). Constructs that link the two coding exons of c-myc to the long terminal repeat (LTR) of Ha-MS virus were introduced into the 3T3 fibroblasts. The steady state levels of exogenous c-myc mRNA in the individual stable clones were 3-10 fold higher than the endogenous mRNA levels in non transfected Balb/c 3T3 cells. The expression directed from the c-myc-construct was found to be completely resistant to inhibition by IFN while it was still partially responsive to addition or depletion of growth factors. To test the possible phenotypic changes after this genetic manipulation, the cell cycle distribution of individual c-myc-transfected clones was analyzed during the growth factor controlled transition from resting phase to proliferating state. We find that entry into S phase of the c-myc-transfected clones became completely resistant to inhibition by low IFN concentrations which blocked this process in the parental cell line and the control clones. It is concluded that deregulated expression of c-myc resulting from substitution of the authentic promoters and the first c-myc exon with a viral promoter reduces the sensitivity of synchronized fibroblasts to the antimitogenic effects of IFN.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006131:Growth Inhibitors / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects; D051379:Mice; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D006131:Growth Inhibitors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D007372:Interferons