Transcription profiling of lapatinib treated of breast cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Priti Hegde
PROVIDER: E-MEXP-440 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles.
Hegde Priti S PS Rusnak David D Bertiaux Melissa M Alligood Krystal K Strum Jay J Gagnon Robert R Gilmer Tona M TM
Molecular cancer therapeutics 20070501 5
Lapatinib (GW572016) is a small-molecule dual inhibitor of epidermal growth factor receptor (ErbB1) and ErbB2 receptor kinase activities currently in phase III clinical trials. We used phosphoprotein and microarray analyses to carry out targeted pathway studies of phosphorylation and gene expression changes in human breast cancer cell lines in the presence or absence of lapatinib. Studies were done in four breast cancer cell lines, two of which were responsive and two of which were nonresponsive ...[more]
Similar Datasets
Project description:To obtain an integrated view of gene regulation in response to environmental and endogenous estrogens on a genome-wide scale, we performed ChIP-seq, to identify estrogen receptor 1 (ER) binding sites, and RNA-seq in endometrial cancer cells exposed to bisphenol A (BPA; found in plastics), genistein (GEN; found in soybean), or 17β-estradiol (E2; an endogenous estrogen). GEN and BPA treatment induces thousands of ER binding sites and >50 gene expression changes, representing a subset of E2‑induced gene regulation changes. Genes affected by E2 were highly enriched for ribosome-associated proteins; however, GEN and BPA failed to regulate most ribosome-associated proteins and instead enriched for transporters of carboxylic acids. Treatment-dependent changes in gene expression were associated with treatment-dependent ER binding sites, with the exception that many genes up-regulated by E2 harbored a BPA-induced ER binding site, but failed to show any expression change after BPA treatment. GEN and BPA exhibited a similar relationship to E2 in the breast cancer line T-47D, where cell type specificity played a much larger role than treatment specificity. Overall, both environmental estrogens clearly regulate gene expression through ER on a genome-wide scale, although with lower potency resulting in less ER binding sites and less gene expression changes compared to the endogenous estrogen, E2. RNA-seq of human cancer cell lines treated with estradiol, bisphenol A, genistein or DMSO (control)
2012-06-13 | E-GEOD-38234 | biostudies-arrayexpress
Project description:Comparison of brain gene expression between silver foxes selected for tame behavior and non-selected silver fox.
2005-12-31 | E-MEXP-451 | biostudies-arrayexpress
Project description:Transcription factors (TFs) can relay signals through temporal alterations in their levels. The cell stress responsive TF p53 exhibits different dynamics depending on the type of stress, which influence the magnitude and dynamics of expression of its target genes and subsequent cellular outcomes. The mechanisms decoding p53 dynamics into levels and dynamics of RNA and protein of its targets remain unclear. We systematically quantified p53 target mRNA and protein levels over time under two p53 dynamical regimes – oscillatory and sustained – using RNA-seq and quantitative mass spectrometry. We categorized the mRNA dynamical patterns arising from oscillatory or sustained p53 expression, as well as the corresponding protein dynamics. We found that in both cases oscillatory dynamics allowed for the greatest variety of dynamical patterns of the downstream species. Target proteins from a wide range of functional categories were induced under both p53 dynamic conditions, with induction levels being overall higher under sustained dynamics. Mathematical modeling combined with analysis of empirical data revealed three mechanisms of decoding p53 dynamics: adjustment of mRNA and protein degradation rates, adjustment of activation thresholds for expression of mRNA and corresponding protein levels, and usage of coherent and incoherent feed-forward loop motifs in generating exclusive responses to p53 oscillatory or sustained dynamics, respectively. Our results highlight the diversity of mechanisms that decode complex TF dynamics into dynamical patterns of mRNA and proteins.
2022-02-11 | PXD027030 | Pride
Project description:Bacillus anthracis Sterne 34F2 cells were grown in the absence of and in the presence of different concentrations of paraquat and hydrogen peroxide. Additionally, a deletion mutant strain lacking the sodA1 gene was also assayed with and without the addition of different concentrations of paraquat.
2007-04-12 | E-MEXP-1043 | biostudies-arrayexpress
Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens. Total of 28 arrays included in this study, which corresponding to 9 individuals with paired pre/post treatment samples and an additional 10 untreated control individuals. pair_analysis_normData.txt for paired analysis of pre/post treatment; ordinary_analysis_normData.txt for non-paired analysis include all samples, except for 38 Pax V0 and 56 Pax V1, which shows technicial bias and lowest array quality, hence removed from analysis.
2011-08-29 | E-GEOD-31729 | biostudies-arrayexpress
Project description:Inferring in humans biological responses to external cues such as drugs, chemicals, viruses and hormones, is an essential question in biomedicine and cannot be easily studied in humans. Thus, biomedical research has continuously relied on animal models for studying the impact of these compounds and attempted to M-^StranslateM-^T the results to humans. In this context, the Systems Biology Verification for Industrial Methodology for Process Verification in Research (SBV IMPROVER) initiative had run a Species Translation Challenge for the scientific community to explore and understand the limit of translatability from rodent to human using systems biology. Therefore, a multi-layer omics dataset was generated that comprised of phosphoproteomics, transcriptomics and cytokine data derived from normal human (NHBE) and rat (NRBE) bronchial epithelial cells exposed in parallel to more than 50 different stimuli under identical conditions. The present manuscript describes in detail the experimental settings, the generation, processing and quality control analysis of the multi-layer omics dataset. The datasets are accessible in public repositories could be leveraged for further translation studies.
2014-06-10 | E-MTAB-2091 | biostudies-arrayexpress
Project description:Starting with our early global expression analyses of TCDD-treated human hepatoma cells {Puga, 2000 4679 /id}, the AHR transcriptional induction profile has been extensively studied, whether activated by TCDD, B[a]P or in the absence of exogenous ligands (reviewed in {Frericks, 2007 5618 /id}). In addition to using prior knowledge to integrate expression profiles into the AHR gene target network, we performed a new set of expression profile analyses of wild type Hepa-1c1c7 and c35 cell lines and compared the responses in naïve cells with responses in TCDD or B[a]P exposed cells for 8 hours. Results of our expression array studies are in close agreement with current knowledge. Experiment Overall Design: Three biological replicates were each performed for wildype naïve cells (DMSO), TCDD activated cells, and B[a]P activated cells, and for c35 (AHR mutant) naïve cells (DMSO), TCDD activated cells, and B[a]P activated cells.
2009-04-25 | E-GEOD-11796 | biostudies-arrayexpress
Project description:T-47 cells were treated with rapamycin, 3-methyladenine (3MA)-rapamycin and vehicle (DMSO, control) in a time series manner (1, 8, 24 and 48h), Affymetrix Genechip U133 Plus 2.0 array were used to compare the gene expression patterns of rapamycin-treated, 3MA-rapamycin treated versus control cells. All experiments were carried out in triplicates and a total of 24 chips were used. 3MA-Rapamycin treated samples were only limited to 24 h as total RNA for 48h was degraded.
2012-01-11 | E-MEXP-3487 | biostudies-arrayexpress
Project description:The amyloid beta (Aβ) peptide represents a 37 to 49 amino acids endoproteolytic fragment of the amyloid precursor protein. The cellular biology that governs the formation and clearance of Aβ has been understood to play a critical role in Alzheimer’s disease (AD). The primary objective of this study was to generate an in-depth inventory of human brain proteins that oligomeric preparations of Aβ1-42 can bind to using an unbiased in vitro discovery approach. Synthetic Aβ1-42 peptides and a brain extract generated from adult human frontal lobe tissue served in these studies as baits and biological source material, respectively. oAβ1-42 was prepared by aggregating the peptide at 4 ºC for 24 h, using previously described procedures known to generate amyloid-β-derived diffusible ligands (ADDLs). Because the interaction with a given binding partner may rely on a binding epitope that comprises N- or C-terminal residues of Aβ1-42, two separate experiments (I and II) were conducted, which differed in the orientation the oAβ1-42 bait was tethered to the affinity matrix. To facilitate meaningful comparisons across experiments, the method of Aβ1-42 capture was not based on immunoaffinity reagents. Instead, alternative Aβ1-42 baits were equipped with biotin moieties attached to the N- or C-terminus by a 6-carbon linker chain, enabling their consistent affinity-capture on streptavidin agarose matrices. Biotin-saturated streptavidin agarose matrices served as negative controls and three biological replicates of samples and controls were generated for each of the three separate interactome datasets by reproducing the affinity-capture step side-by-side on three separate streptavidin agarose affinity matrices that had been saturated with the biotinylated baits. To identify differences in protein-protein interactions of monomeric versus oligomeric Aβ1-42, a 3rd interactome experiment was conducted in which oAβ1-42-biotin or mAβ1-42-biotin served as baits. Digitonin-solubilized brain extracts, which are known to comprise extracellular and most cellular proteins (except for nuclear proteins) served as biological starting material, consistent with the main subcellular areas previously reported to harbor Aβ. Following extensive washes of affinity matrices in their protein-bound state, binders to the bait peptides were eluted by rapid acidification, fully denatured in 9 M urea, and trypsinized. To avoid notorious confounders related to variances in the subsequent handling and analysis of samples, individual peptide mixtures were labeled with distinct isobaric tandem mass tags (TMT) in a six-plex format, then combined and concomitantly subjected to ZipTip-based pre-analysis clean-up by strong cation exchange (SCX) and reversed phase (RP) separation. Four-hour split-free reversed phase nanospray separations were online coupled to an Orbitrap Fusion Tribrid mass spectrometer, which was configured to run an MS3 analysis method.
2017-07-05 | PXD004867 | Pride
Project description:We previously noted that combination glucocorticoids and PI3K inhibition induces synergistic cell death. To identify genes involved in myeloma cell death we examined mRNA expression in each individual treatment and in the combination. The glucocoriticoid resistant cells (MM.1RL) are used as a negative control. Gene expression is assessed using Illumina Human HT-12v4 bead chips For this experiment, the lab is using human multiple myeloma cell lines that were isolated from a patient. MM.1S cells display sensitivity to glucocorticoids. MM.1RL cells display resistance to glucocorticoid treatment due to spontaneous mutations that render the glucocorticoid receptor inoperable. In this experiment, there will be 4 conditions for the MM.1S cells, and 2 conditions for the MM.1RL cells. We will be treating the MM.1S cells with a glucocorticoid alone (Dexamethasone - 1 uM), a PI3K inhibitor alone (LY249002 - 25 uM), a combination of the two drugs, and a vehicle control. The MM.1RL cells will be treated with a PI3K inhibitor alone, and with a vehicle control. Since the PI3K inhibitor is diluted in DMSO, as a control an equal volume of DMSO will be added to all conditions not containing the PI3K inhibitor. Conditions within the MM.1S cell line will be compared with each other. Specifically, we hope to identify genes that are similarly affected by all three experimental conditions. The MM.1RL conditions will not be analyzed at this time. There will be 4 biological replicates of each condition.
2015-12-07 | E-GEOD-64704 | biostudies-arrayexpress