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Platform
GSE42781
Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The Epidermal Growth Factor Receptor 2 (ERBB2 or HER2) is amplified and overexpressed in approximately 20% of invasive breast cancers and is associated with metastasis and poor prognosis. Here we describe the role of a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells. Overexpression of Delta-HER2 in human mammary cells decreased apoptosis and increased proliferation and expression of epithelial-to-mesenchymal markers. It also induced invasion in three-dimensional cultures and promoted tumorigenicity and metastasis in vivo. In contrast, similar overexpression of wild-type HER2 failed to evoke the same effects. Unbiased protein-tyrosine phosphorylation profiling revealed a significant increase in phosphorylation of several key signaling proteins upon Delta-HER2 expression, some of which not previously shown to belong to the HER2 pathway. In addition, microarray analysis revealed the expression of a set of genes specifically associated with Delta-HER2 expression. We found those genes to be highly expressed in ER-negative, high grade and metastatic primary breast tumors. Altogether, these results provide new insights into the function of a tumorigenic splice variant of HER2 and the signaling cascade deriving from its activity
Publication Title
Mammary tumor formation and metastasis evoked by a HER2 splice variant.
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Danio rerio
- 20 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Zebrafish Genome Array (zebrafish)
Description
The mammalian heart has poor regenerative capacity following injury. In contrast, certain lower vertebrates such as zebrafish retain a robust capacity for regeneration into adult life. Here we use an integrated approach to identify evolutionary conserved regenerative miRNA-dependant regulatory circuits in the heart. We identified novel miRNA-dependant networks involved in critical biological pathways, which are differentially utilized between the infarcted mouse heart and the regenerating zebrafish heart.
Publication Title
Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.
Sample Metadata Fields
Age, Specimen part
View Samples- Danio rerio
- 8 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
The mammalian heart has poor regenerative capacity following injury. In contrast, certain lower vertebrates such as zebrafish retain a robust capacity for regeneration into adult life. Here we use an integrated approach to identify evolutionary conserved regenerative miRNA-dependant regulatory circuits in the heart. We identified novel miRNA-dependant networks involved in critical biological pathways, which are differentially utilized between the infarcted mouse heart and the regenerating zebrafish heart. Overall design: 2 conditions, 4 biological replicates per condition
Publication Title
Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 8 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The mammalian heart has poor regenerative capacity following injury. In contrast, certain lower vertebrates such as zebrafish retain a robust capacity for regeneration into adult life. Here we use an integrated approach to identify evolutionary conserved regenerative miRNA-dependant regulatory circuits in the heart. We identified novel miRNA-dependant networks involved in critical biological pathways, which are differentially utilized between the infarcted mouse heart and the regenerating zebrafish heart.
Publication Title
Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
The mammalian heart has poor regenerative capacity following injury. In contrast, certain lower vertebrates such as zebrafish retain a robust capacity for regeneration into adult life. Here we use an integrated approach to identify evolutionary conserved regenerative miRNA-dependant regulatory circuits in the heart. We identified novel miRNA-dependant networks involved in critical biological pathways, which are differentially utilized between the infarcted mouse heart and the regenerating zebrafish heart. Overall design: 2 conditions, 3 biological replicates per condition
Publication Title
Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Danio rerio
- 48 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impaired tissue regeneration corresponds with altered expression of developmental genes that persists in the metabolic memory state of diabetic zebrafish.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Danio rerio
- 24 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Olsen et al (2010) have shown that induced Diabetes mellitus (DM) in adult Zebrafish results in an impairment of tissue regeneration as monitored by caudal fin regeneration. In those studies, streptozocin was used to induce hyperglycemia in adult zebrafish, and then, following streptozocin withdrawal, a recovery phase was allowed to re-establish euglycemia, due to pancreatic b-cell regeneration. DM-associated impaired fin regeneration continued indefinitely in the metabolic memory state (MM); allowing for subsequent molecular analysis of the underlying mechanisms of MM. This study focuses on elucidating the molecular basis explaining DM-associated impaired fin regeneration and why it persists into the MM state. The analysis of microarray data indicated that of the 14,900 transcripts analyzed, aberrant expression of 71 genes relating to tissue developmental and regeneration processes were identified in DM fish and the aberrant expression of these 71 genes persisted into the MM state. Key regulatory genes of major signal transduction pathways were identified among this group of 71; and therefore, these findings provide a possible explanation for how hyperglycemia induces impaired fin regeneration and why it continues into the MM state.
Publication Title
Impaired tissue regeneration corresponds with altered expression of developmental genes that persists in the metabolic memory state of diabetic zebrafish.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Danio rerio
- 24 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Olsen et al (2010) have shown that induced Diabetes mellitus (DM) in adult Zebrafish results in an impairment of tissue regeneration as monitored by caudal fin regeneration. In those studies, streptozocin was used to induce hyperglycemia in adult zebrafish, and then, following streptozocin withdrawal, a recovery phase was allowed to re-establish euglycemia, due to pancreatic b-cell regeneration. DM-associated impaired fin regeneration continued indefinitely in the metabolic memory state (MM); allowing for subsequent molecular analysis of the underlying mechanisms of MM. This study focuses on elucidating the molecular basis explaining DM-associated impaired fin regeneration and why it persists into the MM state. The analysis of microarray data indicated that of the 14,900 transcripts analyzed, aberrant expression of 71 genes relating to tissue developmental and regeneration processes were identified in DM fish and the aberrant expression of these 71 genes persisted into the MM state. Key regulatory genes of major signal transduction pathways were identified among this group of 71; and therefore, these findings provide a possible explanation for how hyperglycemia induces impaired fin regeneration and why it continues into the MM state.
Publication Title
Impaired tissue regeneration corresponds with altered expression of developmental genes that persists in the metabolic memory state of diabetic zebrafish.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Smyd3 is a histone methyltransferase implicated in tumorigenesis. Here we show that Smyd3 expression in mice is required but not sufficient for chemically induced liver and colon cancer formation. In these organs Smyd3 is functioning in the nucleus as a direct transcriptional activator of several key genes involved in cell proliferation, epithelial-mesenchymal transition, JAK/Stat3 oncogenic pathways, as well as of the c-myc and b-catenin oncogenes. Smyd3 specifically interacts with H3K4Me3-modified histone tails and is recruited to the core promoter regions of many but not all active genes. Smyd3 binding density on target genes positively correlates with increased RNA Pol-II density and transcriptional outputs. The results suggest that Smyd3 is an essential transcriptional potentiator of a multitude of cancer-related genes. Overall design: Standard Smyd3-deficient (Smyd3-KO) mice were generated using gene-trap ES cell clones (AS0527 from International Gene Trap Consortium), in which a selection cassette, containing the splice acceptor site from mouse EN2 exon 2 followed by the beta-galactosidase and neomycin resistance gene fusion gene and the SV40 polyadenylation sequence was inserted into the 5th intron of the Smyd3 gene. The resulting mice were devoid of Smyd3 mRNA and protein in all tissues, including liver and colon. For the generation of Smyd3-Tg mice the open reading frame of the mouse Smyd3 cDNA, which contained 3 Flag epitopes at the 3’ end was inserted into the StuI site of the pTTR1-ExV3 plasmid (Yan et al, 1990). The 6.8 kb HindIII fragment containing the mouse transthyretin enhancer/promoter, intron 1, Smyd3 cDNA, three Flag epitopes and SV40 poly-A site was used to microinject C57Bl/6 fertilized oocytes. Founder animals were identified by Southern blotting and crossed with F1 mice to generate lines. Specific overexpression in the liver was tested by RT-PCR analysis in different tissues.
Publication Title
Smyd3 Is a Transcriptional Potentiator of Multiple Cancer-Promoting Genes and Required for Liver and Colon Cancer Development.
Sample Metadata Fields
No sample metadata fields
View Samples