We 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Specimen part, Treatment
View SamplesFor both CD4 and micropajfe cell types, upregulated genes were primarily related to immune activation and proliferation, while down-regulated genes represented more diverse processes, including cell membranes, vasculature development, cell adhesion, and lipid-related metabolic processes.
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Specimen part, Treatment
View SamplesFor both CD4 and micropajfe cell types, upregulated genes were primarily related to immune activation and proliferation, while down-regulated genes represented more diverse processes, including cell membranes, vasculature development, cell adhesion, and lipid-related metabolic processes.
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Specimen part, Treatment
View SamplesIn wild-type mice, expression of chemokines that are ligands for Ccr2, Cxcr3, and Cxcr2 increased at days 32 to 41 post-infection, with a return to baseline by day 75. Concomitant increases were seen in Ccr2 and Cxcr3 but not in Cxcr2 expression. Induction of these same factors also occurred in CD40-ligand and CD40 knockout mice but only at a much later time-point, during uncontrolled Pneumocystis pneumonia (PCP). Expression of CD4 Th1 markers was increased in wild-type mice during clearance of infection. Ccr2 and Cx3cr1 knockout mice cleared Pneumocystis infection with kinetics similar to wild-type mice, and all animals developed anti-Pneumocystis antibodies. Upregulation of Ccr2 and Cxcr3 and their ligands supports an important role for T helper cells and mononuclear phagocytes in the clearance of Pneumocystis infection. However, based on the current and prior studies, no single chemokine receptor appears to be critical to the clearance of Pneumocystis.
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Specimen part, Treatment
View SamplesWe examine the transcriptional profile of lung Tgd17 cells from mice that are deficient for Aire compared to wild-type mice. Overall design: Duplicate samples of 500 sorted lung resident CD27- Vg1,2,4,5- gd T cells from
Aire Inhibits the Generation of a Perinatal Population of Interleukin-17A-Producing γδ T Cells to Promote Immunologic Tolerance.
Sex, Age, Specimen part, Cell line, Subject
View SamplesA SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide dosage effect on gene and microRNA expression
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect.
Specimen part, Disease
View SamplesMultiple myeloma (MM) is characterized by marked genomic instability. Beyond structural rearrangements, a relevant role in its biology is represented by allelic imbalances leading to significant variations in ploidy status. To better elucidate the genomic complexity of MM, we analyzed a panel of 45 patients using combined FISH and microarray approaches. Using a self-developed procedure to infer exact local copy numbers for each sample, we identified a significant fraction of patients showing marked aneuploidy. A conventional clustering analysis showed that aneuploidy, chromosome 1 alterations, hyperdiploidy and recursive deletions at 1p and chromosomes 13, 14 and 22 were the main aberrations driving samples grouping. Then, we integrated mapping information with gene and microRNAs expression profiles: a multiclass analysis of the identified clusters showed a marked gene-dosage effect, particularly concerning 1q transcripts, also confirmed by correlating gene expression levels and local copy number alterations. A wide dosage effect affected also microRNAs, indicating that structural abnormalities in MM closely reflect in their expression imbalances. Finally, we identified several loci in which genes and microRNAs expression correlated with loss-of-heterozygosity occurrence. Our results provide insights into the composite network linking genome structure and gene/microRNA transcriptional features in MM.
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect.
Specimen part, Disease
View SamplesSmall nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may play a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM), by profiling puri?ed malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCL) and 4 normal controls. Overall, a global sno/scaRNAs down-regulation was found in MMs and at more extent in sPCLs compared to normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the TC4 MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by imprinting mechanism at 15q11. However, the imprinting center resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information into the bio-molecular complexity of plasma cell dyscrasias.
The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma.
Specimen part, Disease, Disease stage
View Samples