Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from human breast cancer cell lines after demethylation treatment

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE28968: MRNA expression data from human breast cancer cell lines after demethylation treatment. GSE28969: MicroRNA expression data from human breast cancer cell lines after demethylation treatment. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Ramin Radpour

PROVIDER: E-GEOD-28976 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.

Radpour Ramin R Barekati Zeinab Z Kohler Corina C Schumacher Martin M MM Grussenmeyer Thomas T Jenoe Paul P Hartmann Nicole N Moes Suzette S Letzkus Martin M Bitzer Johannes J Lefkovits Ivan I Staedtler Frank F Zhong Xiao Yan XY

PloS one 20111104 11

<h4>Background</h4>The contribution of aberrant DNA methylation in silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations are reversible, it became of interest to determine the effects of the 5-aza-2'-deoxycytidine (DAC) demethylation therapy in breast cancer at different molecular levels.<h4>Methods and findings</h4>Here we investigate a synoptic model to predict complete DAC treatment effects at the level of genes, microRNAs and prote ...[more]

PMID: 22076154

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Project description:ERM-NM-117p is a synthetic peptide corresponding to the sequence P295LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERM-NM-1) and initially synthesized to mimic its calmodulin binding site. ERM-NM-117p was subsequently found to elicit estrogenic responses in E2-deprived ERM-NM-1-positive breast cancer cells, increasing proliferation and E2-dependent gene transcription. Surprisingly, in E2-supplemented media, ERM-NM-117p induced apoptosis and modified the actin network, influencing thereby cell motility. Here, we report that ERM-NM-117p induces a massive early (3h) transcriptional activity in breast cancer cell lines SKBR3). Remarkably, about 75% of the significantly modified transcripts were also modified by E2, confirming the pro-estrogenic profile of ERM-NM-117p. The different ER spectra of the used cell lines allowed us to extract a specific ERM-NM-117p signature related to ERM-NM-1 and its variant ERM-NM-136. With respect to ERM-NM-1, the peptide activates nuclear (cell cycle, cell proliferation, nucleic acid and protein synthesis) and extranuclear signaling pathways. In contrast, through ERM-NM-136 it exerts inhibitory events on inflammation and cell cycle and inhibition of EGFR signaling. This is the first work reporting ERM-NM-136 specific transcriptional effects. The fact that a number ERM-NM-117p-induced transcripts is different from those activated by E2 revealed that the apoptosis and actin modifying effects of ERM-NM-117p are independent from the ER-related actions of the peptide. Cells after a 4h incubation with medium containing 10% charcoal stripped FBS were incubated with or without E2 (10-6M) or ERa17p in RPMI 1640 supplemented with 10% charcoal stripped FBS, for 3 hours. Total RNA was isolated using Nucleospin II columns (Macheray-Nagel, Dttren, Germany), according to the manufacturerM-bM-^@M-^Ys instructions. RNA was labeled and hybridized according to the Affymetrix protocol (Affymetrix Gene-Chip Expression Analysis Technical Manual), using the HGU133A plus 2 chip, analyzing a total of 54675 transcripts. Signals were detected by an Affymetrix microarray chip reader.

Dataset Information

Expression data from human breast cancer cell lines after demethylation treatment

Publications

Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.

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