Transcription profiling of human oesophageal cells stimulated with a low pH environment
Ontology highlight
ABSTRACT:
Missing data files: GSM38763.CEL (Time 0 mins rep 1), GSM38764.CEL (Time 0 mins rep 2), GSM38771.CEL (Time 240 mins rep 1), and GSM38772.CEL (Time 240 mins rep 2).
ORGANISM(S): Homo sapiens
SUBMITTER: Shane Duggan
PROVIDER: E-GEOD-2144 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Low pH induces co-ordinate regulation of gene expression in oesophageal cells.
Duggan Shane P SP Gallagher William M WM Fox Edward J P EJ Abdel-Latif Mohammed M MM Reynolds John V JV Kelleher Dermot D
Carcinogenesis 20050819 2
The development of gastro-oesophageal reflux disease (GORD) is known to be a causative risk factor in the evolution of adenocarcinoma of the oesophagus. The major component of this reflux is gastric acid. However, the impact of low pH on gene expression has not been extensively studied in oesophageal cells. This study utilizes a transcriptomic and bioinformatic approach to assess regulation of gene expression in response to low pH. In more detail, oesophageal adenocarcinoma cell lines were expos ...[more]
Similar Datasets
Project description:The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrettâ??s metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisions with data derived from gene expression studies of Barrettâ??s esophagus and associated adenocarcinoma. Additionally this study may be used to assess divergence in response to bile acids by comparisons with similar study performed in SKGT4 barrett''s assocaited adenocarcinoma cell line. HET-1A cells were exposed to 300um DCA over 24 hours in duplicate experiments including matched timepoint controls
2010-02-28 | E-GEOD-13378 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE13376: Exposure of Barrett's associated adenocarcinoma cell lines SKGT4 to deoxycholic acid (DCA) GSE13378: Exposure of squamous esophageal cell line HET-1A to deoxycholic acid (DCA) Refer to individual Series
2010-03-02 | E-GEOD-13400 | biostudies-arrayexpress
Project description:Comparison of normal adult rat extraocular muscle, cardiac muscle, leg (gastrocnemius-soleus) muscle and smooth muscle (stomach wall). Affymetrix microarray chip RG-U34A was used. MAS version 5 was used to analyze the muscle group differences. Data form part of publication: FASEB Journal 17: 1370-1372, 2003 (full length article available at http://www.fasebj.org/cgi/doi/10.1096/fj.02-1108fje).
2007-10-27 | E-GEOD-142 | biostudies-arrayexpress
Project description:Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer which is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood although genomic sequencing studies have identified several genes encoding chromatin remodeling enzymes that are frequently mutated in OAC. This finding is consistent with the knowledge that one important change that occurs in cancer cells is a reprogramming of the chromatin environment which leads to subsequent changes in their transcriptional profile.
2017-07-07 | E-MTAB-5163 | biostudies-arrayexpress
Project description:Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of <15%, and the incidence is predicted to double within the next 20 years. Current neo-adjuvant chemotherapy treatment strategies only benefit a minority (20-30%) of patients and there are currently no methods available to differentiate between responders and non-responders. Here we performed quantitative proteomics using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) on albumin/IgG-depleted and non-depleted plasma samples from 23 patients with locally advanced OAC or oesophageal gastric junction cancers prior to treatment. Individuals were grouped based on tumour regression (TRG) score (TRG1-3 vs TRG4 and 5) after chemotherapy and differentially abundant proteins were compared using univariate and multivariate analyses. Protein depletion led to the identification of around twice as many proteins in the samples compared to non-depletion. SWATH-MS revealed significant quantitative differences in the abundance of several proteins (p<0.05) between the two groups. These included all three c1q subunit proteins, C1QA, C1QB and C1QC, which were of higher abundance in the low TRG group (higher degree of regression in response to treatment). Of those that were found to be of higher abundance in the high TRG group, GSTP1 was found to exhibit the lowest p-value (univariate analysis) and highest accuracy and Cohen’s kappa value (multivariate analysis). The concentrations of c1q complex and GSTP1 were further examined and validated using ELISA-based assays. This study provides quantitative information relating to differences in the plasma proteome that underpin response to chemotherapeutic treatment in oesophageal cancers.
2022-08-22 | PXD032137 | Pride
Project description:Oesophageal exposure to duodenogastroesophageal refluxate is implicated in the development of BarrettM-bM-^@M-^Ys Metaplasia, with increased risk of progression to oesophageal adenocarcinoma. The literature proposes that reflux exposure activates NF-kB, driving the aberrant expression of intestine-specific caudal-related homeobox genes. However, early events in the pathogenesis of BarrettM-bM-^@M-^Ys Metaplasia from a normal epithelium are poorly understood. To investigate this, our study subjected a 3D model of the normal human oesophageal mucosa to repeated, pulsatile exposure to specific bile components and examined changes in gene expression. Initial 2D experiments with a range of bile salts observed that taurochenodeoxycholate (TCDC) impacted upon NF-kB activation without causing cell death. Informed by this, the 3D human oesophageal model was repeatedly exposed to TCDC in the presence and absence of acid, and the epithelial cells underwent gene expression profiling. We identified ~300 differentially expressed genes following each treatment, with a large and significant overlap between treatments. Enrichment analysis (Broad GSEA, DAVID and MetacoreM-bM-^DM-", GeneGo Inc) identified multiple gene sets related to cell signalling, inflammation, proliferation, differentiation and cell adhesion. Specifically NF-kB activation, Wnt signalling, cell adhesion and targets for the transcription factors PTF1A and HNF4M-NM-1 were highlighted. CDX1/2 transcription factors are believed to play a role in BM development; however, in this study their targets were not enriched, suggesting that CDX1/2 activation may not be the one of the initial events for BM formation. Our findings highlight new areas for investigation in the earliest stages of BM pathogenesis of oesophageal diseases and new potential therapeutic targets. RNA was extracted from oesophageal epithelium grown in a 3D oesophageal mucosa model. The model received pulsatile exposure for 10 mins twice a day for 11 days to pH 7.4 (control, n=6), TCDC (n=6), pH 4 (n=6) or TCDC, pH 4 (n=6). In one experiment, four oesophageal constructs were grown using the epithelial cells from one patient and each construct was exposed to a different insult. The experiment was performed six times using cells from three different patients, repeating each experiment once to produce technical replicates. RNA was then pooled from one technical replicate per patient to produce 8 samples for array analysis. The three treatments were compared to the control.
2013-03-22 | E-GEOD-45380 | biostudies-arrayexpress
Project description:Esophageal cancers (ECs) are highly aggressive tumors with poor prognosis and few treatment options. This study investigated the possibility of treating esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) cells by inhibitors of broad and specific histone deacetylases (HDACi; SAHA, MS-275, FK228) and/or of DNMT (Azacytidine, AZA). Drug targets (HDAC1,2,3 and DNMT1) were present in non-neoplastic (HET-1A), ESCC (OE21) and EAC (OE33) cell lines. All cell lines responded to HDACi by reduced HDAC activity and increased histone acetylation as well as to AZA by up-regulation of p21. Expression of drug targets remained largely unaffected by HDACi and AZA treatment. Importantly, cell viability, apoptosis, cell cycle dynamics and DNA damage were only affected by HDACi and/or AZA in ESCC and EAC, but not the non-neoplastic cells. This was specifically seen for the combination of MS-275 and AZA, leading to enhanced cancer cell selectivity and drug efficiency. By transcriptome analyses of MS-275, AZA and MS-275/AZA treated cells, known (e.g. p21) as well as novel regulated genes significantly associated with the cellular effects post HDACi and/or AZA treatment in ESCC and EAC cells were identified. Finally, human EC tissue specimens frequently expressed the actionable drug targets HDAC1/2/3 and DNMT1. In summary, a combined HDACi (MS-275)/AZA treatment is cancer cell selective and efficient in vitro. Since the majority of ECs express the drug targets in situ, this paves the way for further investigations of HDACi/AZA treatment in esophageal cancer cells and their translation into a clinico-pathological setting. To elucidate the transcriptome response to HDAC inhibitors of normal esophageal cells and esophageal tumor cells, total RNA was isolated from non-neoplastic esophageal epithelial cells (Het1A cells) a well as from two esophageal tumor cell lines (OE21 and OE33), respectively. Cells were treated with either MS-275, Azacytidine (AZA) or in combination of both. DMSO treatment was used as control in each case. Total RNA was isolated from cells 24 h after treatment and experiments were performed in biological triplicates.
2015-04-29 | E-GEOD-57130 | biostudies-arrayexpress
Project description:Many biological processes involve post-transcriptional regulation of gene expression by alternative pre-mRNA splicing. Here, we show that an alternative splicing factor SRSF6 affects tissue homeostasis of the skin. In this dataset, we study effects on gene expression and alternative splicing upon SRSF6 overexpression (+doxycycline) in mouse skin using inducible R26-rtTA+/-, ColA1-TREtight-SRSF6+/- transgenic mice 4 mixed-background strain samples (2 SRSF6-induced skin samples and 2 uninduced skin control samples)
2014-01-19 | E-GEOD-52458 | biostudies-arrayexpress
Project description:A cell line (MFD-1) was derived from a 55-year old male with oesophageal adenocarcinoma. Using different sources of genetic material from normal and tumour tissue surgically resected, peripheral blood and the derived cell line a high concordance of genotypes calls across the whole genome confirms MFD-1 was derived from parent tumour. The SNP6 array contained 906,000 probes for the genotyping of SNPs and 946,000 probes for the genotyping of non-polymorphic copy number. Affymetrix CEL files were analysed using the tool PICNIC2 (predicting absolute allele copy number variation with microarray cancer data).
2016-10-03 | E-MTAB-4590 | biostudies-arrayexpress
Project description:Global expression profiling of airway epithelial cells infected with Pseudomonas aeruginosa and the rsmA mutant. Recent work in our laboratory investigated the impact of RsmA on a number of airway epithelial cell phenotypes including actin depolymerization, cytotoxicity and invasion. These cellular phenotypes were influenced by the positive effect of RsmA on the expression of the TTSS in P. aeruginosa (Mulcahy et al. 2006. Infect. Immun.). Pseudomonas aeruginosa is an important opportunistic pathogen which is capable of causing both acute and chronic infections in immunocompromised patients. Successful adaptation of the bacterium to its host environment relies on the ability of the organism to tightly regulate gene expression. RsmA, a small RNA-binding ; protein, controls the expression of a large number of virulence-related genes in P. aeruginosa, including those encoding the type III secretion system and associated effector proteins, with important consequences for epithelial cell morphology and cytotoxicity. In order to examine the influence of RsmA-regulated functions in ; the pathogen on gene expression in the host, we compared global expression profiles of airway epithelial cells in response to infection with P. aeruginosa PAO1 and an rsmA mutant. The RsmA-dependent response of host cells was characterized by significant changes in the global transcriptional pattern, including the increased expression of two Kruppel-like factors, KLF2 and KLF6. This increased expression was mediated by specific type III effector proteins. ExoS was required for the enhanced expression of KLF2, whereas both ExoS and ExoY were required for the enhanced expression of KLF6. Neither ExoT nor ExoU influenced the expression of the transcription factors. Additionally, the increased gene expression of KLF2 and KLF6 was associated with ExoS-mediated cytotoxicity. Therefore, this study identifies for the first time the human transcription factors ; KLF2 and KLF6 as targets of the P. aeruginosa type III exoenzymes S and Y, with potential importance in host cell death. Experiment Overall Design: RNA isolation and microarray sample preparation Experiment Overall Design: Biological samples from two independent infection experiments were used in two independent microarray experiments as outlined below. Total RNA was isolated from epithelial cells using a RNeasy Kit (Qiagen) according to manufacturer's instructions. Genomic DNA was removed using DNA-free (Ambion) and confirmed by PCR to be free of DNA, prior to cDNA synthesis. Isolated RNA was used in the preparation of fragmented cRNA for microarray hybridization according to the manufacturer's protocol (Affymetrix). Briefly, 8.5ug of RNA was converted to double stranded cDNA by reverse transcription, using a Superscript cDNA synthesis kit (Invitrogen), with an oligo dT primer containing a T7 RNA polymerase site added 3' of the poly (T) (Affymetrix). After second strand synthesis, cDNA was converted to biotin-labelled cRNA by in vitro transcription (Enzo). The labelled cRNA was purified using Genechip clean up module (Qiagen). Total cRNA quality and yield was measured using a GeneQuant spectrophotometer and 20ug of cRNA was fragmented at 94ºC for 35 mins in fragmentation buffer (40 mM tris acetate, pH 8.1, 100 mM potassium acetate, 30 mM magnesium acetate). Full length and fragmented cRNA sample integrity was assessed by electrophoresis on a 1% agarose-TBE gel visualized by staining with SyBr green. Fragmented cRNA was sent to MRC geneservice (Cambridge, UK) for assessment of RNA quality using a Bioanalyzer (Agilent) before hybridization and scanning. The arrays were washed and stained in a fluidics station and scanned according to the manufacturer's protocols (Affymetrix). Experiment Overall Design: Microarray data analysis Experiment Overall Design: Raw image analysis was performed using Microarray Suite v5.0 software (Affymetrix). Downstream data analysis was performed using GeneSight software version 2.7 (Biodiscovery). For all analyses, the signal intensities from two independent infection and microarray experiments were used. Statistically significant changes in gene expression were identified by firstly performing analysis of variance (ANOVA), for comparison between multiple groups, with a P value of < 0.05. The list of transcripts generated using ANOVA was then subjected to a Student's t-test, for comparison between two groups, with a P value of < 0.05. To identify different levels of gene expression compared to baseline, a fold change cut-off of greater than or equal to 1.5 was applied to this data.
2007-10-27 | E-GEOD-4485 | biostudies-arrayexpress