15-25% of breast cancers (BC) show ERBB2-amplification and overexpression of the encoded ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs may help understand their behavior and design new therapeutic strategies. In this study, we defined the high resolution genome and gene expression profiles of 54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. We first identified the ERBB2-C17orf37-GRB7 genomic segment as the minimal common amplicon, and CRKRS and IKZF3 as the most frequent centromeric and telomeric amplicon borders, respectively. Second, we identified 17 genome regions affected by copy number aberration (CNA). The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in ERBB2-amplified BCs. The genomic profiles of estrogen receptor-postive (ER+) and negative (ER-) ERBB2-amplified BCs were different. The WNT/-catenin signaling pathway was involved in ER- ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes associated with ER+ ERBB2-amplified BCs. The size of the ERBB2-amplicon was different in inflammatory (IBC) and non inflammatory BCs. ERBB2-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. We have shown that ERBB2 BCs are heterogeneous and identified genomic features that may be useful in the design of therapeutical strategies
Genome profiling of ERBB2-amplified breast cancers.
No sample metadata fields
View SamplesWe performed gene expression pofiling of Zeb2cKO and control sciatic nerves and identified significantly changed genes ZEB2 is also known as SIP1 Overall design: 4 RNA-Seq samples from P7 sciatic nerves of Ctrl and Zeb2 cKO mice (duplicatess, Ctrl and cKO)
Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination.
Specimen part, Subject
View SamplesAfter-ripening induced seed dormancy release in wheat is associated with mRNA oxidation.
Integrated analysis of seed proteome and mRNA oxidation reveals distinct post-transcriptional features regulating dormancy in wheat (Triticum aestivum L.).
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identical gene regulation patterns of T3 and selective thyroid hormone receptor modulator GC-1.
Sex, Age, Specimen part, Cell line
View SamplesWheat seed germination and seminal root growth can be inhibited by treatment with exogenous ABA
Regulation of wheat seed dormancy by after-ripening is mediated by specific transcriptional switches that induce changes in seed hormone metabolism and signaling.
Specimen part
View SamplesSynthetic selective thyroid hormone (TH) receptor (TR) modulators (STRMs) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver and insulin resistance in preclinical animal models. STRMs differ from native THs in preferential binding to the TR subtype versus TR, increased uptake into liver and reduced uptake into other tissues. However, selective modulators of other nuclear receptors (NRs) exhibit important gene-selective actions which have been attributed to differential effects on receptor conformation and dynamics and these effects can have profound influences in animals and humans. While there are suggestions that STRMs could exhibit such gene-specific actions, the extent to which these effects are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, triiodothyronine (T3), and the prototype STRM GC-1 induce identical gene-sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TR, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency versus T3, at angiopoietin-like factor 4 (ANGPTL4) in HepG2. Investigation of the latter effect confirms that GC-1 acts through TR to directly induce this gene. However, this gene-selective GC-1 activity is not related to unusual T3 response element (TRE) sequence, unlike previously documented promoter-selective STRM actions. Together, our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRMs will be subtle and rare.
Identical gene regulation patterns of T3 and selective thyroid hormone receptor modulator GC-1.
Specimen part, Cell line
View Samples[1] Lactic acidosis time course: MCF7 cells were exposed to lactic acidosis for different length of time. We used microarrays to examine the genomic programs of cells incubated under lactic acidosis for different length of time
Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.
Cell line, Treatment
View SamplesFetal and neonatal beta cells have poor glucose-induced insulin secretion and only gain robust glucose responsiveness several weeks after birth. This unresponsiveness may be due to a generalized immaturity of the metabolic pathways normally found in beta cells.
Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells.
No sample metadata fields
View SamplesGene expression profiling of Peditric Burkitt lymphoma (PBL) patients samples were performed to analyze the comparative genomic signature and to investigate targetable signaling pathways in PBL
Comparative genomic expression signatures of signal transduction pathways and targets in paediatric Burkitt lymphoma: a Children's Oncology Group report.
Sex, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Three-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancer.
Specimen part, Cell line
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