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MRNA expression data from human breast cancer cell lines after demethylation treatment

ABSTRACT: The contribution of aberrant DNA methylation and the downstream effects in tumorogenesis through silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations can be reversed, we investigated the effects of the epigenetic therapy in breast cancer cell lines. We used microarrays to investigate the global gene expression profile after demethylation treatment with 5-aza-2’-deoxycytidine (DAC) in breast cancer cell lines and identified distinct classes of early and late systematic stable or transient effects of the treatment. Three selected breast cell lines including MDA-MB231 (a highly aggressive cell line), SKBR3 (a non-aggressive cell line) and HB2 (a breast epithelial cell line as control) were subject for RNA isolation before treatment, after treatment with DAC and at five point follow-ups (1st, 3rd, 5th, 7th and 10th passages) at “drug holiday” condition and hybridized on Affymetrix microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Radpour R

PROVIDER: S-ECPF-GEOD-28968 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Project description:Breast cancer is a genetically and phenotypically complex disease. To understand the role of microRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer (BC) cell lines to discover miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations.Using a microarray carrying LNA™ modified oligonucleotide capture probes (Exiqon), expression levels of 725 human miRNAs were measured in 51 BC cell lines. MiRNA expression was explored by unsupervised cluster analysis and then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer. Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 BC cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of BC cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters of which half were related to the ER-status of the cell lines. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group of cell lines, 39 miRNAs were associated with ERBB2 overexpression and 24 miRNAs with E-cadherin gene mutations, which are frequent in this subtype of BC cell lines. In contrast, 31 different miRNAs were associated with E-cadherin promoter hypermethylation, which, contrary to E-cadherin mutation, is exclusively observed in BC cell lines that are not of luminal origin. The differential expression of 30 miRNAs were associated with p16INK4 status while only a few differentially expressed miRNAs were associated with BRCA1, or PIK3CA/PTEN, TP53 mutation status of the cell lines (P-value < 0.05). Twelve miRNAs were associated with DNA copy number variation of the respective locus. Luminal-basal and epithelial-mesenchymal associated miRNAs determine the overall subdivision of miRNA transcriptome of BC cell lines. Specific sets of miRNAs were associated with ERBB2 overexpression, p16INK4aor E-cadherin mutation or E-cadherin methylation status, which implies that these miRNAs may contribute to the driver role of the genetic aberrations. Additionally, miRNAs, which are located in a genomic region showing recurrent genetic aberrations, may themselves play a driver role in breast carcinogenesis or contribute to a driver gene in their vicinity. In short, our study provides detailed molecular miRNA portraits of BC cell lines, which can be exploited for functional studies of clinically important miRNAs. Affymetrix plus2PM arrays were hybridized according to the manufacturer's procedure using RNA extracted from 52 cultured breast cancer cell lines. Most cellines were analyzed in triplicate. Gene expression data in log2 scale arrays were calculated and associated with diverse characteristics. This submission represents the gene expression component of the study only

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MRNA expression data from human breast cancer cell lines after demethylation treatment

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