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| Status |
Public on Dec 16, 2006 |
| Title |
Tumor suppression by Interferon regulatory factor-1 relies on down-regulation of cyclin D1 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Interferons have been ascribed to mediate antitumor effects. IRF-1 is a major target gene of interferons. 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 non-transformed cells by IRF-1. These include cell cycle regulating genes. Activation of IRF-1 decreases cyclin D1 expression and CDK4 kinase activity concomitant with dephosphorylation of pRb. These effects of IRF-1 are mediated by inhibition of the MEK-ERK pathway and a transcriptional repression of cyclin D1. IRF-1 mediated effects on cell cycle progression were found to be overridden by ectopic expression of cyclin D1. Ablation of cyclin D1 by RNA interference experiments prevents transformation and tumor growth in nude mice. The data demonstrate that cyclin D1 is a key target for IRF-1 mediated tumor suppressive effects.
Keywords: NIH3T3 cells, myc, ras, IRF-1, proliferation, transformation, G1/S cell cycle ceckpoint
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| Overall design |
3 samples were analysed, two replicates per sample. NIH3T3 cells were compared with myc/ras transformed NIH3T3 cells and with IRF1 expressing myc/ras transformed cells.
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| |
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| Contributor(s) |
Geffers R, Kroger A |
| Citation(s) |
17409403 |
| |
| Submission date |
Dec 11, 2006 |
| Last update date |
Feb 18, 2018 |
| Contact name |
Robert Geffers |
| E-mail(s) |
robert.geffers@helmholtz-hzi.de
|
| Phone |
+49 531-6181-3058
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| Organization name |
HCI - Helmholtz Centre for Infection Research
|
| Department |
Dep. Molecular Bacteriology
|
| Lab |
Genome Analytics
|
| Street address |
Inhoffenstr. 7
|
| City |
Braunschweig |
| ZIP/Postal code |
38124 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA98679 |
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