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. 1995 Jan;18(1-2):67-75.
doi: 10.1007/BF00744321.

Proliferation control of mammalian cells by the tumor suppressor IRF-1

M Köster  1 , S Kirchhoff, F Schaper, H Hauser
Affiliations

Proliferation control of mammalian cells by the tumor suppressor IRF-1

M Köster et al. Cytotechnology. 1995 Jan.

Abstract

We have attempted to establish a system in which cell proliferation is controlled by a physiological regulator. Interferon regulatory factor 1 (IRF-1) is a transcription factor that recognizes a sequence which is present in the interferon-β promoter as well as in the promoters of interferon-inducible genes. IRF-1 acts as a tumor suppressor. Constitutive overexpression of recombinant IRF-1 leads to inhibition of cell growth. The extent of this growth arrest depends on the intracellular concentration of IRF-1. In order to allow IRF-1 expression in various mammalian cells we have established two different systems for conditional IRF-1 transcription and activation, respectively. In one case, an inducible promoter, in the other case a fusion protein composed of IRF-1 and the hormone-binding domain of the human estrogen receptor was used. Both systems allow to control gradually the growth of mammalian cell lines by adjusting the intracellular concentration of IRF-1 via estradiol or tetracycline in the medium. Despite the activity of IRF-1 as an antiproliferative agent the expression of certain proteins is retained. Moreover, expression of genes which are controlled by IRF-1 responsive promoters is enhanced.

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