IRF-1 reverts the transformed phenotype of oncogenically transformed cells in vitro and in vivo

Kröger, Andrea; Dallügge, Andreas; Kirchhoff, Sabine; Hauser, Hansjörg

doi:10.1038/sj.onc.1206260

Cited by 55 publications

(50 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IRF-1 reverses IRF-2-induced transformation of NIH3T3 cells and tumor formation in nude mice . IRF-1 inhibits anchorage-independent growth of cells transformed by various oncogenes and overexpression of IRF-1 inhibits tumor formation in syngeneic mice Yim et al, 1997;Kirchhoff and Hauser, 1999;Kroger et al, 2001;Kroger et al, 2003). Although there is no spontaneous tumor development in IRF-1À/À mice, IRF-1/p53 double-deficient mice have increased tumor incidence and enhanced multiplicity and alteration of tumor spectrum, when compared to p53À/À mice alone (Nozawa et al, 1999).…”

Section: Irf-1 Expression Is Elevated In Normal Cells and Is Induced mentioning

confidence: 99%

Central role of interferon regulatory factor‐1 (IRF‐1) in controlling retinoic acid inducible gene‐I (RIG‐I) expression

Sarkar

Emdad

et al. 2007

Journal Cellular Physiology

View full text Add to dashboard Cite

Section: Irf-1 Expression Is Elevated In Normal Cells and Is Induced mentioning

confidence: 99%

Central role of interferon regulatory factor‐1 (IRF‐1) in controlling retinoic acid inducible gene‐I (RIG‐I) expression

Sarkar

Emdad

et al. 2007

Journal Cellular Physiology

View full text Add to dashboard Cite

“…The inhibition of transformation by different oncogenes and the growth-suppressive effects in different kinds of cancer cells suggest that a key pathway is targeted by IRF-1 (5,6).…”

Section: Introductionmentioning

confidence: 99%

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

Kröger

Stirnweiß²,

Pulverer³

et al. 2007

Cancer Research

View full text Add to dashboard Cite

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 signalregulated 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 tumorsuppressive effects. [Cancer Res 2007;67(7):2972-81]

show abstract

“…Both intrinsic and systemic responses including adaptive immunity have been linked to IRF-1-induced tumor suppression (11,12,16). Here, we show that neither intrinsic nor adaptive effects but innate defense mechanisms play a key role in IRF-1 induced inhibition of lung metastases.…”

Section: Discussionmentioning

confidence: 73%

“…Ectopic expression of IRF-1 in tumor cells shows inhibition of proliferation and tumorigenicity (16,21). These effects are mediated by the inhibition of cell-cycle progression or induction of apoptosis and require comparably high levels of IRF-1 protein (11).…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of IRF-1 inhibits proliferation, reverses transformation (16), and induces tumor-specific immune responses (11,17). To determine the mechanisms of IRF-1 on metastasis formation, we generated a CT26HA tumor cell line expressing IRF-1 under the control of a tetracyclinedependent promoter (CT26HA/IRF-1).…”

Section: Irf-1 Decreases Metastatic Tumor Growth and Prolongs Survivamentioning

confidence: 99%

See 1 more Smart Citation

IRF-1 Expression Is Essential for Natural Killer Cells to Suppress Metastasis

et al. 2011

Self Cite

View full text Add to dashboard Cite

IFN-g promotes tumoral immune surveillance, but its involvement in controlling metastases is less clear. Using a mouse model of pulmonary metastases, we show that local IFN-g treatment inhibits formation of metastases through its regulation of IRF-1 in tumor cells. IRF-1 is an IFN-g-induced transcription factor pivotal in the regulation of infection and inflammation. IRF-1 blockade abolished the inhibitory effect of IFN-g on tumor metastases, whereas ectopic expression of IRF-1 phenocopied the inhibitory effects of IFN-g. IRF-1 did not affect the survival of tumor cells in the circulation or their infiltration into lungs, but it was essential to support the pulmonary attraction and activation of natural killer (NK) cells. Depleting NK cells from mice abolished the protective effect of IFN-g or IRF-1 on metastases. In addition, cytotoxicity assays revealed that tumor cells expressing IRF-1 were targeted more effectively by NK cells than IRF-1 nonexpressing tumor cells. Moreover, NK cells isolated from lungs inoculated with IRF-1-expressing tumor cells exhibit a greater cytotoxic activity. Mechanistic investigations revealed that IRF-1-induced NK cell cytotoxicity was independent of perforin and granzyme B but dependent on the NK cell activating receptor DNAM-1. Taken together, our findings establish IRF-1 as an essential mediator of the cross-talk between tumor cells and NK cells that mediate immune surveillance in the metastatic niche. Cancer Res; 71(20); 6410-8. Ó2011 AACR.

show abstract

IRF-1 reverts the transformed phenotype of oncogenically transformed cells in vitro and in vivo

Cited by 55 publications

References 46 publications

Central role of interferon regulatory factor‐1 (IRF‐1) in controlling retinoic acid inducible gene‐I (RIG‐I) expression

Central role of interferon regulatory factor‐1 (IRF‐1) in controlling retinoic acid inducible gene‐I (RIG‐I) expression

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

IRF-1 Expression Is Essential for Natural Killer Cells to Suppress Metastasis

Contact Info

Product

Resources

About