Barrett's esophagus is characterized by the replacement of squamous epithelium with specialized intestinal metaplastic mucosa. The exact mechanisms of initiation and development of Barrett's metaplasia remain unknown, but a hypothesis of successful adaptation against noxious reflux components has been proposed. To search for the repertoire of adaptation mechanisms of Barrett's metaplasia, we employed high-throughput functional genomic and proteomic methods that defined the molecular background of metaplastic mucosa resistance to reflux. Transcriptional profiling was established for 23 pairs of esophageal squamous epithelium and Barrett's metaplasia tissue samples using Affymetrix U133A 2.0 GeneChips and validated by quantitative real-time polymerase chain reaction. Differences in protein composition were assessed by electrophoretic and mass-spectrometry-based methods. Among 2,822 genes differentially expressed between Barrett's metaplasia and squamous epithelium, we observed significantly overexpressed metaplastic mucosa genes that encode cytokines and growth factors, constituents of extracellular matrix, basement membrane and tight junctions, and proteins involved in prostaglandin and phosphoinositol metabolism, nitric oxide production, and bioenergetics. Their expression likely reflects defense and repair responses of metaplastic mucosa, whereas overexpression of genes encoding heat shock proteins and several protein kinases in squamous epithelium may reflect lower resistance of normal esophageal epithelium than Barrett's metaplasia to reflux components. Despite the methodological and interpretative difficulties in data analyses discussed in this paper, our studies confirm that Barrett's metaplasia may be regarded as a specific microevolution allowing for accumulation of mucosal morphological and physiological changes that better protect against reflux injury.
Molecular defense mechanisms of Barrett's metaplasia estimated by an integrative genomics.
Sex, Age
View SamplesGastrointestinal stromal tumours (GISTs) represent a heterogeneous group of tumours of mesenchymal origin characterized by gain-of-function mutations in KIT or PDGFRA of the type III receptor tyrosine kinase family. Although mutations in either receptor are thought to drive an early oncogenic event through similar pathways, two previous studies reported the mutation-specific gene expression profiles. However, their further conclusions were rather discordant. To clarify the molecular characteristics of differentially expressed genes according to GIST receptor mutations, we combined microarray-based analysis with detailed functional annotations.
Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression.
Sex, Specimen part, Disease stage
View SamplesTotal RNA from three replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by histone H2A^4-20 mutant.
Regulation of gene transcription by the histone H2A N-terminal domain.
No sample metadata fields
View SamplesTotal RNA from three replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by the histone H2A K4,7G mutant.
Regulation of gene transcription by the histone H2A N-terminal domain.
No sample metadata fields
View SamplesTotal RNA from two replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by histone H3 K4,36,79G mutant.
Genetic and genomewide analysis of simultaneous mutations in acetylated and methylated lysine residues in histone H3 in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesTotal RNA from two replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by histone H3 K4,9,14,18,23,27,36,79G mutant.
Genetic and genomewide analysis of simultaneous mutations in acetylated and methylated lysine residues in histone H3 in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Simultaneous mutation of methylated lysine residues in histone H3 causes enhanced gene silencing, cell cycle defects, and cell lethality in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesTotal RNA from three replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by histone H2B K111A mutant.
Novel functional residues in the core domain of histone H2B regulate yeast gene expression and silencing and affect the response to DNA damage.
No sample metadata fields
View SamplesTotal RNA from three replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by histone H2B R102A mutant.
Novel functional residues in the core domain of histone H2B regulate yeast gene expression and silencing and affect the response to DNA damage.
No sample metadata fields
View SamplesTotal RNA from three replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by H3 K4,79R mutant.
Simultaneous mutation of methylated lysine residues in histone H3 causes enhanced gene silencing, cell cycle defects, and cell lethality in Saccharomyces cerevisiae.
No sample metadata fields
View Samples