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GSE54483
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sadanandam et al. (2013) recently published a study based on the use of microarray data to classify colorectal cancer (CRC) samples. The classification claimed to have strong clinical implications, as reflected in the paper title: A colorectal cancer classification system that associates cellular phenotype and responses to therapy. They defined five subtypes: (i) inflammatory; (ii) goblet-like; (iii) enterocyte; (iv) transit-amplifying; and (v) stem-like. Based on drug sensitivity data from 21 patients, they also reported that the so-called stem-like subtype show differential sensitivity to FOLFIRI. This is the key result in their publication, since it implies a direct relation between the subtype and the choice of CRC therapy (i.e. FOLFIRI response). However, our analyses using the same drug sensitivity data and results from additional patients showed that the CRC classification reported by Sadanandam et al. is not predictive of FOLFIRI response.
Publication Title
Colorectal cancer classification based on gene expression is not associated with FOLFIRI response.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
p21-activated kinases (Paks) play an important role in oncogenic signaling pathways, and have therefore been considered as potential therapeutic targets in various cancers. Most studies of Pak function employ loss of function methods such as gene knock-out or knock-down, but these approaches result in loss of both the enzymatic and scaffolding properties of these proteins, and thus may not reflect the effects of small molecule inhibitors that block catalytic function. In this study we use a new transgenic mouse model in which a specific peptide inhibitor of Group I Paks (Pak1, -2, and -3) is conditionally expressed in response to Cre recombinase. Using this model, we show that inhibition of endogenous Pak function impedes the transition of adenoma to carcinoma in an Apc-driven mouse model of colorectal cancer. These effects are mediated by inhibition of Wnt signaling through reduced ß-catenin activity as well as suppression of an epithelial-mesenchymal transition program mediated by miR-200 and Snai1. These results highlight the potential therapeutic role of Pak1 inhibitors in colorectal cancer and suggest new therapeutic strategies in this disease. Overall design: We generated a targeted transgenic mouse carrying a conditionally activated PID allele at the Rosa26 locus, and showed that expression of this allele effectively inhibited the activity of Group I Paks in vivo. To assess the global molecular effects of Pak inhibition in Apc-null CRC cells, we next explored the effect of repressing Pak activity on transcription. Total RNA was extracted from PID+ and PID- cells and RNA-sequencing was preformed, followed by pathway analysis and qPCR validation for selected mRNAs.
Publication Title
Group I Paks are essential for epithelial- mesenchymal transition in an Apc-driven model of colorectal cancer.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
To study the development and function of “natural-arising” T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3+ CD4+ Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) ß-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR ß-chain was able to provide stronger TCR signals. This TCR-ß–driven mechanism would thus unify former per se contradicting hypotheses of TCR-dependent and -independent nTreg development. Strikingly, peripheral FoxP3- CD4+ T cells expressing the same TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate into Th1 cells but were poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells. Overall design: We performed RNA-Seq analysis to determine the transcriptional differences between monoclonal FoxP3GFP-positive and -negative CD4+ T cells from NOD.TCRab.FoxP3GFP.Rag-/- and compared it with polyclonal FoxP3GFP-positive and -negative CD4+ T cells from NOD.FoxP3GFP mice
Publication Title
Nuclear transfer nTreg model reveals fate-determining TCR-β and novel peripheral nTreg precursors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Copper-based chemotherapeutic compounds Casiopeinas, have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis -in a process mediated by reactive oxygen species- for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions; before establishing settings and parameters needed for their wide clinical application.
Publication Title
Whole genome gene expression analysis reveals casiopeína-induced apoptosis pathways.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient derived xenograft (PDX) models is a promising platform to for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine environment on the gene expression of the engrafted human tumoral cells. We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data from PDAC and hepatocellular carcinoma (HCC). Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable one from the other based in their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models are clearly different and more similar to their original tumor than to PDX models from the other tumor type. Interestingly, the main differences between pancreatic PDX models and human PDAC is the expression of genes involved in pathways related with extracellular matrix interactions and cell cycle regulation likely reflecting the adaptations of the tumors to the new environment. Furthermore, most of these differences are detected in the first passages after the tumor engraftment, indicating early phases of the adaptation process. In conclusion, different from conventional cancer cell lines, PDX models of PDAC retain similar gene expression profiles of PDAC. Expression changes are mainly related to genes involved in stromal pathways likely reflecting the adaptation to new environments. We also provide evidence of the stability of gene expression patterns over subsequent passages.
Publication Title
Transcriptional dissection of pancreatic tumors engrafted in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the tumor epithelium are poorly understood. The signaling adapter p62 has been implicated as a positive regulator of epithelial tumorigenesis; however, its role in the stroma is unknown. We show here that p62 levels are reduced in the stroma of several tumors. Also, orthotopic and organotypic studies demonstrate that the loss of p62 in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism. Inhibition of the pathway by p62 deficiency results in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through modulation of metabolism in the tumor stroma.
Publication Title
Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression. Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events. Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.
Publication Title
The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We analyzed liver gene expression from male and female ARE-Del mice, which have prolonged and chronic expression of IFN gamma through deletion of the IFN gamma 3’ UTR AU-rich element. Overall design: Compare liver gene expression from male and female ARE-Del compared to control littermates (n=3)
Publication Title
Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Danio rerio
- 17 Downloadable Samples
- IlluminaGenomeAnalyzerII, IlluminaHiSeq2000
Description
Long non-coding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in human and mouse have annotated lncRNAs expressed in cell lines and adult tissues, but a systematic analysis of lncRNAs expressed during vertebrate embryogenesis has been elusive. To identify lncRNAs with potential functions in vertebrate embryogenesis, we performed a time series of RNA-Seq experiments at eight stages during early zebrafish development. We reconstructed 56,535 high-confidence transcripts in 28,912 loci, recovering the vast majority of expressed RefSeq transcripts, while identifying thousands of novel isoforms and expressed loci. We defined a stringent set of 1,133 non-coding multi-exonic transcripts expressed during embryogenesis. These include long intergenic ncRNAs (lincRNAs), intronic overlapping lncRNAs, exonic antisense overlapping lncRNAs, and precursors for small RNAs (sRNAs). Zebrafish lncRNAs share many of the characteristics of their mammalian counterparts: relatively short length, low exon number, low expression, and conservation levels comparable to introns. Subsets of lncRNAs carry chromatin signatures characteristic of genes with developmental functions. The temporal expression profile of lncRNAs revealed two novel properties: lncRNAs are expressed in narrower time windows than protein-coding genes and are specifically enriched in early-stage embryos. In addition, several lncRNAs show tissue-specific expression and distinct subcellular localization patterns. Integrative computational analyses associated individual lncRNAs with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first comprehensive identification of lncRNAs in a vertebrate embryo and forms the foundation for future genetic, genomic and evolutionary studies. Overall design: RNA-Seq for 8 zebrafish developmental stages, 2 lanes for each stage (3 for shield).
Publication Title
Ribosome profiling reveals resemblance between long non-coding RNAs and 5' leaders of coding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples