Modulation of nuclear proto-oncogene expression and cellular growth in myeloid leukemic cells by human interferon alpha

✍ Scribed by Adele H. Marshall; Deborah Alper; John Hiscott

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 820 KB
• Volume: 135
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041350221

✦ Synopsis

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-a1, and IFN-P1 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 (rlFN-a2). 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, rlFN-a2 treatment alone stimulated fos mRNA 1 1 -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-a1 or IFN-P, gene expression was observed in KG-1 or U937 cells. These results demonstrate that exogenous rlFN-a2 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.