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Transcription profiling of rat REF52 cells reveals an E2F1-dependent gene expression program that determines the balance between proliferation and cell death

ABSTRACT: E2F1 has been shown to induce both proliferation and apoptosis. We now show that PI3K/Akt signaling regulates the balance of these events by specifically blocking expression of genes in the E2F1 apoptotic program but not the proliferative program. Experiment Overall Design: 11 samples total, two replicates each (except Sample 1 which is represented once)

ORGANISM(S): Rattus norvegicus

SUBMITTER: Timothy Hallstrom

PROVIDER: E-GEOD-9496 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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An E2F1-dependent gene expression program that determines the balance between proliferation and cell death.

Hallstrom Timothy C TC Mori Seiichi S Nevins Joseph R JR

Cancer cell 20080101 1

The Rb/E2F pathway regulates the expression of genes essential for cell proliferation but that also trigger apoptosis. During normal proliferation, PI3K/Akt signaling blocks E2F1-induced apoptosis, thus serving to balance proliferation and death. We now identify a subset of E2F1 target genes that are specifically repressed by PI3K/Akt signaling, thus distinguishing the E2F1 proliferative or apoptotic function. RNAi-mediated inhibition of several of these PI3K-repressed E2F1 target genes, includi ...[more]

PMID: 18167336

Similar Datasets

An E2F1-Dependent Gene Expression Program That Determines the Balance Between Proliferation and Cell Death

Project description:E2F1 has been shown to induce both proliferation and apoptosis. We now show that PI3K/Akt signaling regulates the balance of these events by specifically blocking expression of genes in the E2F1 apoptotic program but not the proliferative program. Keywords: PI3K dependent modulation of E2F1 gene expression measured by Affymetrix gene expression analysis

2007-11-02 | GSE9496 | GEO

Expression data from U2OS ER-E2F1 cells after FOXO knockdown and E2F1 activation

Project description:Effect of FOXO knockdown on E2F1-mediated transcription U2OS cells stably expressing ER-E2F1 were infected with two different lentiviruses both targeting FOXO1 and FOXO3 or control virus encoding scrambled sequence. Twenty four hours post infection medium was replaced to serum-free DMEM for 24 hours. Then medium was replaced to serum-free DMEM with or without 20 nM 4-hydroxy tamoxifen for 6 hours.

2012-07-05 | E-GEOD-39136 | biostudies-arrayexpress

Expression data from lenses triply deficient for E2F1, E2F2, and E2F3 transcription factors

Project description:The E2F family consists of transcriptional repressors and activators that control cell proliferation. In the classic paradigm of cell cycle regulation, the three activators, E2F1, E2F2 and E2F3, are invariably depicted as the final components of a CDK/Rb signaling cascade that executes the transcriptional program necessary to commit cells to enter S phase. Unexpectedly, we find through analysis of Affymetrix expression array data that mature lens epithelial cells deficient for E2F1-3 fail to repress cell cycle-regulated genes (and other targets of E2F) and that this corresponds with subsequent apoptosis and cellular collapse in the lens. Murine lenses were collected at two stages of development for RNA extraction and hybridization on Affymetrix microarrays. Our aim was to determine key events that lead to cellular collapse of lenses triply deficient for E2F1, E2F2, and E2F3 in neonates.

2010-06-23 | E-GEOD-16533 | biostudies-arrayexpress

Cross-platform prediction of gene expression signatures.

Project description:We developed a method to convert gene expression signatures across the Illumina and Affymetrix platforms. We generated an E2F1 signature. We processed RNA for E2F1, MYC, and Ras signatures on the Illumina platform. 16 Melanoma samples are also included for validation.

2013-08-21 | E-GEOD-50051 | biostudies-arrayexpress

Screening of new target genes specifically activated by deregulated E2F

Project description:To identify genes specifically activated by deregulated E2F, we examined gene expression profiles using human normal fibroblasts (HFFs), which were starved of serum and re-stimulated with serum, over-expressed with E2F1 or expressed with adenovirus E1a to forcedly inactivate RB. To identify genes activated by growth stimulation, human normal fibroblasts (HFFs) were starved of serum for 48 hr, infected with control virus, restimulated with serum or left serum-starved for 18 hr and harvested. To identify genes actived by deregulated E2F, HFFs were starved of serum for 48 hr, infected with control virus, adenovirus expressing E2F1 or adenovirus E1a, further cultured in the absence of serum for 18 hr and harvested. Gene expression profiles of ecach sample were examined by DNA microarray.

2015-11-20 | E-GEOD-67887 | biostudies-arrayexpress

An E2F1-dependent gene expression program that determines the balance between proliferation and cell death.

Project description:The Rb/E2F pathway regulates the expression of genes essential for cell proliferation but that also trigger apoptosis. During normal proliferation, PI3K/Akt signaling blocks E2F1-induced apoptosis, thus serving to balance proliferation and death. We now identify a subset of E2F1 target genes that are specifically repressed by PI3K/Akt signaling, thus distinguishing the E2F1 proliferative or apoptotic function. RNAi-mediated inhibition of several of these PI3K-repressed E2F1 target genes, including AMPK alpha 2, impairs apoptotic induction by E2F1. Activation of AMPK alpha 2 with an AMP analog further stimulates E2F1-induced apoptosis. We also show that the presence of the E2F1 apoptotic expression program in breast and ovarian tumors coincides with good prognosis, emphasizing the importance of the balance in the E2F1 proliferation/apoptotic program.

| S-EPMC2243238 | biostudies-literature

Transcription profiling of Drosophila E2f/Rb genetic pathway manipulation

Project description:We demonstrate that the cell cycle regulators, E2f /Dp and Rb, control the transcription of ribosomal proteins (RP) in Drosophila embryos. Mutation of E2f1 or Dp and over expression of Rbf1 increase and reduce RP transcription, respectively. Although E2f/Dp/Rb might exert this effect through a repressor complex, the regulatory regions of RP genes do not show an enrichment of canonical E2f binding sites. In addition, E2f1, Dp and Rbf1 also regulate the expression of RACK1, a ribosomal component and a negative regulator of cell cycle progression. These findings strengthen the coupling of cell cycle regulation to protein biosynthesis. Experiment Overall Design: Our study examines the genomic response of intact Drosophila embryos to the genetic manipulation of E2F/Rb pathway molecules. For over-expression experiments, Arm-Gal4 stocks were crossed to UAS-gene stocks for the following genes: E2f1/Dp, E2f2/Dp, Rbf1, and E2f1336-805 (a dominant negative form of E2f1 lacking the DNA binding domain) [16]. The E2f17172 and E2f191 null alleles were balanced by TM3[Kr-GFP]. Dpa2 and Dpa4 null alleles were balanced by CyO[Kr-GFP]. 14-16 hr E2f17172/E2f191 null mutant embryos were hand selected based on the absence of fluorescent Bolwigâs organs in Kr-GFP balanced stocks using a Zeiss stereomicroscope equipped with epifluorescence. E2f17172/E2f191 and Dpa2/Dpa4 null mutant embryos (8-10h) were selected using the COPASTM SELECT system for automated sorting of multi-cellular organisms. Eighteen RNA samples, two from each cross, were obtained from approximately 200 to 700 embryos per sample. For each cross, 2 h embryo collections were aged for 8 to 14 h at 25oC, quick frozen in an ethanol/dry ice mixture, and stored at -80 oC. The RNA was prepared for microarray analysis in accordance with Affymetrix instructions.

2008-06-15 | E-GEOD-7655 | biostudies-arrayexpress

E2F1 ChIP-Seq on mouse hepatocytes overexpressing E2F1

Project description:E2F transcription factors are known regulators of the cell cycle, proliferation, apoptosis and differentiation. We reveal an essential role for E2F1 in liver through the regulation of glycolysis and lipogenesis. E2F1 deficiency leads to a decreased in glycolysis and de novo synthesis of fatty acids in hepatocytes. ChIP-Seq was performed to determine direct tagets of E2F1 in hepatocytes. We highlight that E2F1 directly binds the promoters of genes implicated in metabolic process and notably key lipogenic genes to control these pathways.

2015-12-01 | GSE74006 | GEO

p21 Regulates Wnt-Notch Balance via DREAM/MMB/Rb-E2F1 and Maintains Intestinal Stem Cell Homeostasis

Project description:The crosstalk and balance regulation of Wnt-Notch have been known to be essential for cell fate decision and tissue regeneration, while how the balance is maintained and how the Wnt-Notch pathways are connected with the cell cycle regulation are still not clear. In the mouse model with accelerated aging phenotypes due to the loss of cell cycle inhibitor p21 function in Werner syndrome background, we observed the imbalance of Wnt-Notch signaling, along with the fast turnover of intestinal epithelia, which might cause the abnormal mobilization of stem cells, exhaust the stem cell reservoir, and result in the accelerated aging phenotypes. We revealed that the loss of p21 caused the shift of DREAM/Rb complex to MMB/E2F1 complex and the fast turnover of intestinal epithelia. Importantly, we identified the E2F1 as the transcriptional regulator for Notch1, which connected the p21-DREAM/MMB/Rb-E2F1 pathway with Wnt-Notch pathway. The overexpression of p21 rescued the imbalance of Wnt-Notch pathway. Our data identify p21 as an important factor in maintaining sequential mobilization, proliferation, and homeostasis of intestinal stem cells.

2023-12-10 | GSE248188 | GEO

Identification of the immunomodulatory properties of the E2F1-induced melanoma secretome on CD4+ or CD8+ immune cells as characterized by Affymetrix microarrays

Project description:This study elucidates the effect of the E2F1-regulated melanoma-secreted factors on the phenotype and transcriptional program of immune cells (CD4+ T and CD8+ T cells) in the melanoma immune microenvironment. In order to determine the immune modulatory effect of the secretome on immune cells, we established a co-culture system where different melanoma cell lines (high-E2F1/invasive and low E2F1/non-invasive) were co-cultured with CD4+ or CD8+ T cells without direct interaction. These data describe the transcriptomes of immune cells and for the two melanoma cell lines Mel147 and C8161, both in co- and monoculture condition, with stable E2F1 knockdowns and corresponding controls.

2024-10-27 | E-MTAB-12750 | biostudies-arrayexpress

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