E-GEOD-6505 - Transcription profiling of mouse NIH3T3 cells were compared with myc/ras transformed NIH3T3 cells and with IRF1 expressing myc/ras transformed cells
Submitted on 11 December 2006, released on 14 June 2008, last updated on 27 March 2012
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. Experiment 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.
transcription profiling by array, unknown experiment type
Tumor suppression by IFN regulatory factor-1 is mediated by transcriptional down-regulation of cyclin D1. Andrea Kröger, Anja Stirnweiss, Julia Elisabeth Pulverer, Katjana Klages, Martina Grashoff, Jörg Reimann, Hansjörg Hauser. Cancer Res 67(7):2972-81 (2007)