Insulin like growth factor 1 (IGF-1) has a central role in mammalian hearing and hearing loss. The auditory and vestibular systems form the inner ear and have a common developmental origin. During chicken early development IGF-1 modulates neurogenesis of the cochleovestibular ganglion but no further studies have been conducted to explore the potential role of IGF-1 in the vestibular system.
Comparative gene expression study of the vestibular organ of the Igf1 deficient mouse using whole-transcript arrays.
Specimen part
View SamplesChromosomal instability (CIN) is thought to be a source of mutability in human cancer. However, CIN is highly deleterious for the cell, and the resulting aneuploidy induces metabolic stress and compromises cell fitness. Here we utilized the X-chromosome dosage compensation mechanism and changes in X-chromosome number to demonstrate in Drosophila epithelial cells the causal relationship between CIN, aneuploidy, gene dosage imbalance and tumorigenesis. Whereas the harmful effects of CIN can be buffered by resetting the X-chromosome dosage compensation to compensate for changes in X-chromosome number, interfering with the mechanisms of dosage compensation suffices to induce tumorigenesis. In addition, multiple mechanisms buffer the deleterious effects of CIN including DNA-damage repair, activation of the p38 signalling pathway, and induction of cytokine expression to promote compensatory cell proliferation. These data reveal a key role of gene dosage imbalances to CIN-induced programmed cell death and tumorigenesis and the existence of robust compensatory mechanisms.
Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis.
Specimen part
View SamplesComparison of transcriptional profile of CD8 cytotoxic T lymphocytes terated with the mTORC1 inhibitor rapamycin or the mTOR inhibitor KU-0063794 and comparison with proteomic analysis.
The cytotoxic T cell proteome and its shaping by the kinase mTOR.
Specimen part, Treatment
View SamplesThe emergence of immune resistance variants during immunotherapy is poorly understood. We generated a highly immune resistant cell line (P3) from a susceptible cell line (P0) by subjecting it to 3 rounds of in vivo immune selection. Subsequently, microarray analysis of P0 and P3 was performed to identify genes that may contribute to the increase in immune resistance.
Ectopic expression of vascular cell adhesion molecule-1 as a new mechanism for tumor immune evasion.
No sample metadata fields
View SamplesIdentification of genes that are differentially regulated in fibroblasts derived from dysplastic oral mucosa and oral squamous cell carcinoma compared to fibroblasts derived from normal oral mucosa.
Identification of two distinct carcinoma-associated fibroblast subtypes with differential tumor-promoting abilities in oral squamous cell carcinoma.
Sex, Age, Specimen part
View SamplesWe studied the effects of acute activation of the melanoma oncogene RAC1 P29S using a tamoxifen-inducible ER-fusion protein system in mouse melanocytes Overall design: An ER-RAC1 P29S fusion protein was stably expressed in the spontaneously immortalized mouse melanocyte cell line melan-a. The fusion protein was activated by treatment with 500 nM 4OH-tamoxifen. RNA was isolated and sequenced at 0 h, 4 h and 40 h post-treatment. The gene expression profiles at 4 h and 40 h were compared to the 0 h time-point. To control for effects induced by 4OH-tamoxifen independent from ER-RAC1 P29S, we performed the same experiment in melan-a cells transduced with an empty vector.
RAC1<sup>P29S</sup> Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance.
Subject
View SamplesWe studied the effects of endogenous expression of the melanoma oncogene RAC1 P29S in BRAF V600E;PTEN hemizygous mouse melanomas. Overall design: Transgenic mice with a conditional knock-in of the P29S mutation in the endogenous Rac1 locus were generated and crossed onto C57BL/6J, Tyr-CreER;BrafCA/wt;Ptenfl/wt mice. Melanomas were induced by topical 4OH-tamoxifen. We compared the gene expression profile in whole tumour lysates from Tyr-CreER+/-;Ptenfl/wt;BrafCA/wt;Rac1LSL-P29S/wt mice versus Tyr-CreER+/-;Ptenfl/wt;BrafCA/wt;Rac1wt/wt mice (n = 6 tumours from 5-6 animals per group).
RAC1<sup>P29S</sup> Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance.
Cell line, Subject
View SamplesComparatative gene expression analysis for CD4 T cell subsets isolated from peripheral blood and palatine tonsils
A methodology for global validation of microarray experiments.
Specimen part
View SamplesDNA microarrays are popular tools for measuring gene expression of biological samples. This ever increasing popularity is ensuring that a large number of microarray studies are conducted, many of which with data publicly available for mining by other investigators. Under most circumstances, validation of differential expression of genes is performed on a gene to gene basis. Thus, it is not possible to generalize validation results to the remaining majority of non-validated genes or to evaluate the overall quality of these studies. <br></br> We have devised an approach for the global validation of DNA microarray experiments that will allow researchers to evaluate the general quality of their experiment and to extrapolate validation results of a subset of genes to the remaining non-validated genes. We applied this method to a microarray experiment validated with quantitative real time polymerase chain reaction. The experiment consists of three biological replicate treatments of mouse 3T3-L1 preadipocytes with the steroid hormone dexamethasone for 3 hours. Total RNA was extracted from each of our three treatment and three control samples, and we labeled and hybridized five aliquots of each sample to Affymetrix MGU74Av2 microarrays, for a total of 30 microarrays.<br></br> We illustrate why the popular strategy of selecting only the most differentially expressed genes for validation generally fails as a global validation strategy and propose random-stratified sampling as a better gene selection method. We also illustrate shortcomings of often-used validation indices such as overlap of significant effects and the correlation coefficient and recommend the concordance correlation coefficient (CCC) as an alternative.
A methodology for global validation of microarray experiments.
Cell line, Subject, Compound
View SamplesWe report that knockdown of EJC core proteins, eIF4A3, Y14, Magoh, causes a transcript-wide changes in alternative splicing, as well as some transcriptional changes. These changes are specific to EJC core proteins, and KD of UPF1 protein caused different sets of alterantive splicing changes. These changes are linked to the rate of transcription. Overall design: Examination of 4 different knockdown, as well as GFP knockdown in HeLa cells, 2 replicates each condition.
Transcriptome-wide modulation of splicing by the exon junction complex.
No sample metadata fields
View Samples