This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kröger, A. Articles by Hauser, H. Search for Related Content PubMed PubMed Citation Articles by Kröger, A. Articles by Hauser, H.

Tumor Suppression by IFN Regulatory Factor-1 Is Mediated by Transcriptional Down-regulation of Cyclin D1

¹ Department of Gene Regulation and Differentiation, Helmholtz Center for Infection Research, Braunschweig, Germany and ² Department of Internal Medicine, University of Ulm, Ulm, Germany

Requests for reprints: Andrea Kröger, Department of Gene Regulation and Differentiation, Helmholtz Center for Infection Research, Inhoffenstraße 7, D-38124 Braunschweig, Germany. Phone: 49-531-6181-5041; Fax: 49-531-6181-5002; E-mail: andrea.kroeger{at}helmholtz-hzi.de.

IFNs have been ascribed to mediate antitumor effects. IFN regulatory factor-1 (IRF-1) is a major target gene of IFNs. It inhibits cell proliferation and oncogenic transformation. Here, we show that 60% of all mRNAs deregulated by oncogenic transformation mediated by c-myc and H-ras are reverted to the expression levels of nontransformed cells by IRF-1. These include cell cycle–regulating genes. An indirect target is cyclin D1. Activation of IRF-1 decreased cyclin D1 expression and cyclin-dependent kinase 4 kinase activity concomitant with change in the levels of hyperphosphorylated retinoblastoma protein. These effects are mediated by inhibition of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway and a transcriptional repression of cyclin D1. As shown by in vitro assays and tumor growth in nude mice, IRF-1–mediated effects on cell cycle progression were found to be overridden by ectopic expression of cyclin D1. Conversely, decrease of cyclin D1 by RNA interference experiments prevents transformation and tumor growth. The data show that cyclin D1 is a key target for IRF-1–mediated tumor-suppressive effects. [Cancer Res 2007;67(7):2972–81]

This article has been cited by other articles:

				M. Frontini, M. Vijayakumar, A. Garvin, and N. Clarke A ChIP-chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response Nucleic Acids Res., March 1, 2009; 37(4): 1073 - 1085. [Abstract] [Full Text] [PDF]

				A. Moschonas, M. Kouraki, P. G. Knox, E. Thymiakou, D. Kardassis, and A. G. Eliopoulos CD40 Induces Antigen Transporter and Immunoproteasome Gene Expression in Carcinomas via the Coordinated Action of NF-{kappa}B and of NF-{kappa}B-Mediated De Novo Synthesis of IRF-1 Mol. Cell. Biol., October 15, 2008; 28(20): 6208 - 6222. [Abstract] [Full Text] [PDF]

				E. C. de Bruin, C. J.H. van de Velde, J. H. J.M. van Krieken, C. A.M. Marijnen, and J. P. Medema Epithelial Human Leukocyte Antigen-DR Expression Predicts Reduced Recurrence Rates and Prolonged Survival in Rectal Cancer Patients Clin. Cancer Res., February 15, 2008; 14(4): 1073 - 1079. [Abstract] [Full Text] [PDF]