Premium
Modulation of nuclear proto‐oncogene expression and cellular growth in myeloid leukemic cells by human interferon alpha
Author(s) -
Marshall Adele H.,
Alper Deborah,
Hiscott John
Publication year - 1988
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041350221
Subject(s) - alpha interferon , myeloid cells , alpha (finance) , oncogene , myeloid , microbiology and biotechnology , biology , modulation (music) , interferon , myeloid leukemia , cancer research , cell , virology , cell cycle , genetics , physics , medicine , construct validity , nursing , patient satisfaction , acoustics
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‐β 1 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‐β 1 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.