Activation of multiple growth regulatory genes following inducible expression of IRF-1 or IRF/RelA fusion proteins (original) (raw)

Oncogene volume 15, pages 1425–1435 (1997)Cite this article

Abstract

Interferon Regulatory Factor (IRF)-1 has been characterized as an important growth regulatory and immunomodulatory transcription factor. To further characterize the potential targets of IRF-1 antiproliferative activity, IRF-1 was expressed under the control of the tetracycline-inducible system in murine NIH3T3 cells. Due to their ability to mimic IRF-1 transactivator function, the regulatory potential of IRF-1/RelA and IRF-2/RelA fusion proteins consisting of the DNA binding domains of IRF-1 or IRF-2 fused to the transactivation domain of NF-κB RelA(p65) was also examined. Cells inducibly expressing IRF-1 or IRF/RelA in response to doxycycline treatment displayed significantly reduced growth rates compared to control cells, and inhibition of cell growth correlated directly with the level of transgene expression. Interestingly, IRF-1 and IRF/RelA expression also induced a low level of apoptosis, as detected by microscopic analyses. Furthermore, expression of the interferon inducible, double stranded RNA dependent kinase PKR was increased following IRF-1 or IRF/RelA induction. Most strikingly, induction of IRF-1 and IRF/RelA expression resulted in a significant increase in STAT1 (p91) protein and increased ISGF3 DNA binding activity, suggesting that IRF-1 tumor suppressor activity may involve a novel mechanism which activates the JAK-STAT pathway through STAT1. WAF1 levels were also constitutively elevated in IRF-1 and IRF-1/RelA cells. These studies demonstrate that inducible expression of the transactivation function of IRF-1 or IRF/RelA mediates tumor suppressor activity by inducing cell growth arrest, apoptosis and the differential activation of growth regulatory genes such as PKR, STAT1 and WAF1.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 50 print issues and online access

$259.00 per year

only $5.18 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal, H3T 1E2, Quebec, Canada
    Hannah Nguyen, Rongtuan Lin & John Hiscott
  2. Department of Microbiology and Immunology, McGill University, Montreal, H3T 1E2, Quebec, Canada
    Hannah Nguyen & John Hiscott
  3. Department of Medicine, McGill University, Montreal, H3T 1E2, Quebec, Canada
    Rongtuan Lin & John Hiscott

Authors

  1. Hannah Nguyen
    You can also search for this author inPubMed Google Scholar
  2. Rongtuan Lin
    You can also search for this author inPubMed Google Scholar
  3. John Hiscott
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Nguyen, H., Lin, R. & Hiscott, J. Activation of multiple growth regulatory genes following inducible expression of IRF-1 or IRF/RelA fusion proteins.Oncogene 15, 1425–1435 (1997). https://doi.org/10.1038/sj.onc.1201318

Download citation

Keywords

This article is cited by