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

Cytotechnology
M KösterH Hauser

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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Citations

Oct 12, 1999·Biotechnology and Bioengineering·P P MuellerH Hauser
Mar 29, 2002·Biotechnology and Bioengineering·Katharina SchroederPeter P Mueller
Jan 1, 1996·Cytotechnology·S KirchhoffH Hauser
Nov 13, 2008·Cytotechnology·Darrin KuystermansMohamed Al-Rubeai
Mar 31, 1999·Trends in Biotechnology·M FusseneggerP P Mueller
Oct 18, 2001·Journal of Biotechnology·A V CarvalhalM J Carrondo
Apr 13, 2002·Current Opinion in Biotechnology·Dana C Andersen, Lynne Krummen
Feb 16, 2002·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Andrea KrögerPeter P Mueller
Jun 22, 2000·Biotechnology and Bioengineering·C GeserickP P Mueller
Jul 19, 2013·Biological Chemistry·Christoph LippsDagmar Wirth

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