Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Colon Cancer cell line YB5 untreated cells vs YB5 treated 24h with Depsipeptide at 20 nM

ABSTRACT: Study the effect of HDACi Depsipeptide on gene expression. We combined these data with whole genome DNA methylation microarray to test the reactivation of genes that have an hypermethylated promoter region. We did two independant experiments with 2 untreated and 2 treated different batch of cells

ORGANISM(S): Homo sapiens

SUBMITTER: Noel Raynal

PROVIDER: E-GEOD-34077 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

DNA methylation does not stably lock gene expression but instead serves as a molecular mark for gene silencing memory.

Raynal Noël J-M NJ Si Jiali J Taby Rodolphe F RF Gharibyan Vazganush V Ahmed Saira S Jelinek Jaroslav J Estécio Marcos R H MR Issa Jean-Pierre J JP

Cancer research 20120104 5

DNA methylation is commonly thought of as a "molecular lock" that leads to permanent gene silencing. To investigate this notion, we tested 24 different histone deacetylase inhibitors (HDACi) on colon cancer cells that harbor a GFP locus stably integrated and silenced by a hypermethylated cytomegalovirus (CMV) promoter. We found that HDACi efficiently reactivated expression of GFP and many other endogenous genes silenced by DNA hypermethylation. After treatment, all promoters were marked with act ...[more]

PMID: 22219169

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease characterized by late diagnosis and treatment resistance. Recurrent genetic alterations in defined genes in association with perturbations of developmental cell signaling pathways have been associated with PDAC development and progression. Here, we show that GATA6 contributes to pancreatic carcinogenesis during the temporal progression of pancreatic intraepithelial neoplasia by virtue of Wnt pathway activation. GATA6 is recurrently amplified by both quantitative-PCR and fluorescent in-situ hybridization in human pancreatic intraepithelial neoplasia and in PDAC tissues, and GATA6 copy number is significantly correlated with overall patient survival. Forced overexpression of GATA6 in cancer cell lines enhanced cell proliferation and colony formation in soft agar in vitro and growth in vivo, as well as increased Wnt signaling. By contrast siRNA mediated knockdown of GATA6 led to corresponding decreases in these same parameters. The effects of GATA6 were found to be due to its ability to bind DNA, as forced overexpression of a DNA-binding mutant of GATA6 had no effects on cell growth in vitro or in vivo, nor did they affect Wnt signaling levels in these same cells. A microarray analysis revealed the Wnt antagonist Dickopf-1 (DKK1) as a dysregulated gene in association with GATA6 knockdown, and direct binding of GATA6 to the DKK1 promoter was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift assays. Transient transfection of GATA6, but not mutant GATA6, into cancer cell lines led to decreased DKK1 mRNA expression and secretion of DKK1 protein into culture media. Forced overexpression of DKK1 antagonized the effects of GATA6 on Wnt signaling in pancreatic cancer cells. These findings illustrate that one mechanism by which GATA6 promotes pancreatic intraepithelial neoplasia is by virtue of its activation of canonical Wnt signaling via regulation of DKK1. AsPC1 and A13A cells were stably transfected with a lentivirus expressing mock shRNA or shRNA to GATA6. Each control/shRNA pair (total 4 samples) was analyzed by two-color microarray and the genes commonly dysregulated in both cell lines identified.

Dataset Information

Colon Cancer cell line YB5 untreated cells vs YB5 treated 24h with Depsipeptide at 20 nM

Publications

DNA methylation does not stably lock gene expression but instead serves as a molecular mark for gene silencing memory.

Similar Datasets

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