Recombinant interleukin 2 regulates levels of c-myc mRNA in a cloned murine T lymphocyte

J. C. Reed, D. E. Sabath, R. G. Hoover, M. B. Prystowsky

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The cellular oncogene c-myc has been implicated in the regulation of growth of normal and neoplastic cells. Recently, it was suggested that c-myc gene expression may control the G(0)→G(1)-phase transition in normal lymphocytes that were stimulated to enter the cell cycle by the lectin concanavalin A (Con A). Here we describe the effects of purified recombinant interleukin 2 (rIL2) and of ConA on levels of c-myc mRNA in the noncytolytic murine T-cell clone L2. In contrast to resting (G0) primary cultures of lymphocytes, quiescent L2 cells have a higher RNA content than resting splenocytes and express receptors for interleukin 2 (IL2). Resting L2 cells are therefore best regarded as early G1-phase cells. Purified rIL2 was found to stimulate the rapid accumulation of c-myc mRNA in L2 cells. Levels of c-myc mRNA became maximal within 1 h and declined gradually thereafter. In contrast, ConA induced slower accumulation of c-myc mRNA in L2 cells, with increased levels of c-myc mRNA becoming detectable 4 to 8 h after stimulation. Experiments with the protein synthesis inhibitor cycloheximide demonstrated that the increase in levels of c-myc mRNA that were induced by ConA was a direct effect of this lectin and not secondary to IL2 production. Cyclosporin A, an immunosuppressive agent, markedly reduced the accumulation of c-myc mRNA that was induced by ConA but only slightly diminished the accumulation of c-myc mRNA that was induced by rIL2. Taken together, these data provide evidence that (i) c-myc gene expression can be regulated by at least two distinct pathways in T lymphocytes, only one of which is sensitive to cyclosporin A, and (ii) the accumulation of c-myc mRNA can be induced in T cells by IL2 during the G1 phase of the cell cycle.

Original languageEnglish (US)
Pages (from-to)3361-3368
Number of pages8
JournalMolecular and cellular biology
Volume5
Issue number12
DOIs
StatePublished - Jan 1 1985
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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