Life and Medical Sciences
Cell & Developmental Biology
Wiley InterScience Backfile Collection 1832-2000
To address the mechanisms that regulate expression of specific growth-related nuclear proto-oncogenes, the transcript levels of the c-fos, c-myc, (2′5′)-oligoadenylate synthetase, IFN-α1, and IFN-β1 genes have been measured in the human leukemic cell lines KG-1, U937, and HL-60 following growth stimulation by serum, induction of differentiation by tumor-promoting agents, and/or treatment of cells with exogenously supplied alpha interferon (rIFN-α2). Production of fos and myc RNA was measured by S1 mapping, using fos DNA probes which identified either primary unspliced transcripts or steady-state-spliced mRNA levels, and using a myc probe which spanned the two major c-myc start sites, P1 and P2. Pretreatment of a quiescent KG-1 cell population with IFN for 18 hours before serum addition decreased the stimulation of both fos and myc RNA production. In HL-60 and U937 cells, IFN pretreatment had no inhibitory effect on serum-induced fos or myc transcription; however, in U937, rIFN-α2 treatment alone stimulated fos mRNA 11-fold. Expression of 2′5′ oligoadenylate synthetase was induced in IFN-treated cultures but not in cells stimulated with serum alone. No serum-induced IFN-α1 or IFN-β1 gene expression was observed in KG-1 or U937 cells. These results demonstrate that exogenous rIFN-α2 treatment of quiescent KG-1 cells can antagonize the effect of growth factors by altering expression of nuclear proto-oncogenes, but in general growth inhibition is not obligatorily coupled to inhibition of proto-oncogene transcription.
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