Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human DLD-1 cells stably expressing FOXO3a.A3-ER

ABSTRACT: In order to elucidate how FOXOs affect diverse cellular processes such as cell cycle progression, stress response and transformation we made use of an inducible version of the FOXO3a protein fused to the hormone binding domain of the human estrogen receptor (FOXO3a-A3-ER) in which all three Akt phosphorylation sites have been mutated to alanine. FOXO3a.A3-ER was stably expressed in the human colon carcinoma cell line DLD-1 (Kops et al., 2002b). In order to analyse the transcriptional response to FOXO3a activation we generated gene expression profiles from DL23 or parental DLD-1 cells, after 6 or 24 hours of 4-OHT treatment using cDNA microarrays.

INSTRUMENT(S): ScanArray 4000 [PerkinElmer]

ORGANISM(S): Homo sapiens

SUBMITTER: Almut Schulze

PROVIDER: E-MEXP-721 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression.

Delpuech Oona O Griffiths Beatrice B East Philip P Essafi Abdelkader A Lam Eric W-F EW Burgering Boudewijn B Downward Julian J Schulze Almut A

Molecular and cellular biology 20070423 13

Forkhead transcription factors of the O class (FOXOs) are important targets of the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway. FOXOs have been implicated in the regulation of cell cycle progression, oxidative stress resistance, and apoptosis. Using DNA microarrays, we analyzed the transcriptional response to FOXO3a activation by gene expression analysis in DLD-1 colon cancer cells stably expressing a FOXO3a.A3-ER fusion protein. We found that activation of FOXO3a resulted in repressi ...[more]

PMID: 17452451

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Project description:Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options, CRC shows a poor prognosis with a 5-year survival rate of ~45%. PRDM2/RIZ, a member of Positive Regulatory Domain (PRDM) gene family, expresses two main molecular variants, the PR-plus isoform (RIZ1) and the PR-minus (RIZ2). The imbalance in their expression levels in favour of RIZ2 is observed in many cancer types. The full length RIZ1 has been extensively investigated in several cancers where it acts as a tumour suppressor, whereas few studies have explored the RIZ2 oncogenic properties. PRDM2 is often target of frameshift mutations and aberrant DNA methylation in CRC. Accordingly, our analysis of Exome- and transcriptome public datasets available at The Cancer Genome Atlas (TCGA) portal revealed that PRDM2 gene is frequently mutated and transcriptionally deregulated in CRC. However, little is known about its role in CRC. In this study, we first evaluated the expression of the different PRDM2 transcripts by in silico analysis on TCGA CRC datasets. Our in-silico analysis on TCGA datasets revealed a highly significant downregulation of RIZ1 in CRC samples whereas a RIZ2 increase was observed in the same samples. Then, we assayed several CRC cell lines by qRT-PCR analysis for the main PRDM2 transcripts and selected DLD-1 cell line, which showed the lowest RIZ2 levels to mimic TCGA datasets analysis results and consequently to assess the PRDM2/RIZ2 role in CRC cells. RNAseq analysis revealed that RIZ2 overexpression induced an EGF overexpression suggesting that RIZ2 could be involved in the EGF autocrine regulation of DLD-1 cell behaviour. Noteworthy, the forced RIZ2 expression increased cell viability, growth, colony formation, migration and organoid formation thus confirming our previous findings on HEK-293 cells. These effects could be mediated by the release of high EGF levels by RIZ2 overexpressing DLD-1 cells. Our findings add novel insights on the putative RIZ2 tumor-promoting functions in CRC, although additional attempts are warranted to depict the underlying molecular mechanism of action

Dataset Information

Transcription profiling of human DLD-1 cells stably expressing FOXO3a.A3-ER

Publications

Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression.

Similar Datasets

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