title: Proliferation control of mammalian cells by the tumor suppressor IRF-1.
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.
authors.affiliation: Genetics of Eukaryotes, GBF-Gesellschaft für Biotechnologische Forschung mbH, Mascheroder Weg 1, 38124, Braunschweig, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Köster
authors.forename: S
authors.initials: S
authors.lastname: Kirchhoff
authors.forename: F
authors.initials: F
authors.lastname: Schaper
authors.forename: H
authors.initials: H
authors.lastname: Hauser