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GSE7345
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates cell proliferation, cytoskeletal organization and other signaling networks, and is the most frequent target of activating mutations in cancer. Activating germline mutations of KRAS and HRAS cause severe developmental abnormalities leading to Noonan, cardio-facial-cutaneous and Costello syndrome, but activating germline mutations of NRAS have not been reported. Autoimmune lymphoproliferative syndrome (ALPS) is the most common genetic disease of lymphocyte apoptosis and causes autoimmunity as well as excessive lymphocyte accumulation, particularly of CD4-, CD8- ab T cells. Mutations in ALPS typically affect CD95 (Fas/APO-1)-mediated apoptosis, one of the extrinsic death pathways involving tumor necrosis factor receptor (TNFR) superfamily proteins, but certain ALPS individuals have no such mutations. We show here that the salient features of ALPS as well as a predisposition to hematological malignancies can be caused by a heterozygous germline Gly13Asp activating mutation of the NRAS oncogene that does not impair CD95-mediated apoptosis. The increase in active, GTP-bound NRAS augments RAF/MEK/ERK signaling which markedly decreases the pro-apoptotic protein BIM and attenuates intrinsic, nonreceptor-mediated mitochondrial apoptosis. Thus, germline activating mutations in NRAS differ from other p21 Ras oncoproteins by causing selective immune abnormalities without general developmental defects. Our observations on the effects of NRAS activation indicate that RAS-inactivating drugs, such as farnesyl-transferase inhibitors (FTIs) should be examined in human autoimmune and lymphocyte homeostasis disorders.
Publication Title
NRAS mutation causes a human autoimmune lymphoproliferative syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. Isolation and characterization of viable populations of the constituent cell types of prostate tumors could provide valuable insight into the biology of cancer. The CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between normal and tumor-associated reactive stromal cells. Reactive stroma is characterized by smooth muscle differentiation, prostate down-regulation of SPOCK3, MSMB, CXCL13, and PAGE4, bladder down-regulation of TRPA1, HSD17B2, IL24, and SALL1, and an up-regulation of CXC-chemokines. This study identified a group of differentially expressed genes in CD90+ reactive stromal cells that are potentially involved in organ development and smooth muscle cell differentiation.
Publication Title
Gene expression down-regulation in CD90+ prostate tumor-associated stromal cells involves potential organ-specific genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer cells were MACS sorted from tumor tissue specimem 05-179. Self replicates of CD26+ cancer cells were generated and the expression profiles were determined using Affymetrix U133 Plus 2.0 arrays. These data represent cancer cell type specific transcriptome.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [AltAnalyz probeset-to-Ensembl mapping (huex10st)
Description
A growing body of evidence points to the essential role of bone marrow (BM) tumor microenvironment in Multiple Myeloma (MM) maintenance and progression. Mesenchymal stem cells (MSC) are one of the most important players in this scenario. Through direct and indirect interactions, these cells support MM cells by promoting increase of proliferation, migration, survival, and drug resistance. Additionally, an increasing number of evidence has been demonstrating that MSC from MM patients (MM-MSC) have several abnormalities when compared with their normal counterpart from normal donors (ND-MSC). Therefore, the aimed of our study was to explore the differences between MM-MSC and ND-MSC through gene expression analysis.
Publication Title
Transcriptome Analysis of Mesenchymal Stem Cells from Multiple Myeloma Patients Reveals Downregulation of Genes Involved in Cell Cycle Progression, Immune Response, and Bone Metabolism.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Breast cancer patients present lower 1,25(OH)2D3 or 25(OH)D3 serum levels than unaffected women. Although 1,25(OH)2D3 pharmacological concentrations of 1,25(OH)2D3 may exert antiproliferative effects in breast cancer cell lines, much uncertainty remains about the effects of calcitriol supplementation in tumor specimens in vivo. We have evaluated tumor dimension (ultrassonography), proliferative index (Ki67 expression), 25(OH)D3 serum concentration and gene expression profile, before and after a short term calcitriol supplementation (dose to prevent osteoporosis) to post-menopausal patients. Results: Thirty three patients with operable disease had tumor samples evaluated. Most of them (87.5%) presented 25(OH)D3 insufficiency (<30 ng/mL). Median period of calcitriol supplementation was 30 days. Although tumor dimension did not vary, Ki67 immunoexpression decreased after supplementation. Transcriptional analysis of 15 matched pre/post-supplementation samples using U133 Plus 2.0 GeneChip (Affymetrix) revealed 18 genes over-expressed in post-supplementation tumors. As a technical validation procedure, expression of four genes was also determined by RT-qPCR and a direct correlation was observed between both methods (microarray vs PCR). To further explore the effects of near physiological concentrations of calcitriol on breast cancer samples, an ex vivo model of fresh tumor slices was utilized. Tumor samples from another 12 post-menopausal patients were sliced and treated in vitro with slightly high concentrations of calcitriol (0.5nM), that can be attained in vivo, for 24 hours In this model, expression of PBEF1, EGR1, ATF3, FOS and RGS1 was not induced after a short exposure to calcitriol. Conclusions: In our work, most post-menopausal breast cancer patients presented at least 25(OH)D3 insufficiency. In these patients, a short period of calcitriol supplementation may prevent tumor growth and reduce Ki67 expression, probably associated with discrete transcriptional changes. This observation deserves further investigation to better clarify calcitriol effects in tumor behavior under physiological conditions.
Publication Title
Calcitriol supplementation effects on Ki67 expression and transcriptional profile of breast cancer specimens from post-menopausal patients.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Vitamin D may have anti-tumorigenic actions by influencing the gene expression profile of target tissues, which possess vitamin D receptors. We used a more physiological in vitro model, represented by short-term culture of breast cancer tissue slices, to study the transcriptional effects of a near physiological concentration of calcitriol. Methods. Breast cancer fragments were sliced and maintained in culture for 24 hours in the presence or absence (control) of calcitriol 0.5nM or 100nM (called physiological or supra-physiological concentrations). Five and 16 samples were included in a test or validation group and gene expression was analyzed by microarray (using SAM paired analysis) or qPCR, respectively. Results. Nine genes were regulated by calcitriol 0.5nM including CYP24A1, DPP4, EFTUD1 (FDR0.01), which were up-modulated. However, using a less stringent FDR value (0.25) 61 genes were differentially expressed. Among the down-regulated transcripts were members of the MHC class II complex (HLA-DPA1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB3) and IgG binding (FCGR2A, FCGR2B, FCGR2C). There was an enrichment of genes presenting transcription factor binding sites for vitamin D, among the up-regulated genes and for interferon regulatory factor IRF1, among the down-regulated genes. Analyzing calcitriol supra-physiological effects, a more impressive transcriptional modulation was identified and 136 and 60 genes (FDR 0.1) were more and less expressed in treated samples. Up-regulated genes were involved in vitamin metabolic process, regulation of leukocyte-mediated immunity and positive regulation of alpha-beta T cell activation. Many of the induced genes were already reported as vitamin D responsive genes, including CD14, which was also up-regulated in another set of 16 samples. Genes modulated by both calcitriol concentrations were CYP24A1, DPP4, CA2 (these three in both sets of samples), EFTUD1, TKTL1, KCNK3. Conclusion. Small increments in calcitriol concentration, within the physiological range, for a relatively short period of time may exert transcriptional effects in breast cancer samples. Further studies employing physiological concentrations of vitamin D for longer periods of time may help to elucidate the hormone effects in breast cancer treatment and prevention.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
HER-2 positive breast cancers frequently sustain elevated AKT/mammalian target rapamycin (mTOR) signaling which has been associated with resistance to doxorubicin treatment in the clinic. In our study we investigated if the mTOR inhibitor rapamycin increased the sensitivity to doxorubicin therapy in HB4a, a luminal normal mammary cell line; C5.2, a transformed cell derived from HB4a transfected with HER-2 and SKBR3 that exhibits HER-2 amplification. Flow cytometry analysis showed that the combination treatment for 24 hours with rapamycin 20nM and doxorubicin caused accumulation of HB4a and C5.2 cells in S-G2/M. Otherwise in SKBR3 cells, we observed a relative depletion of cells in S-G2/M and concomitant accumulation in G0/G1 of 10% of the cells. The analysis of IC50 of doxorubicin alone and in combination with rapamycin indicated that the sensitivity was increased 2.37 fold in HB4a, 2.46 in C5.2 and 1.87 in SKBR3, suggesting that rapamycin might have enhanced the effects of doxorubicin. Changes in gene expression resulting from co-treatment demonstrated that functional groups of genes with roles in cell cycle, proliferation, apoptosis regulation were represented in the 3 cells analysed. Other biological functions were exclusively associated with each cell suggesting that the inhibition of mTOR activation induced by HER-2 is complex and depends on the cellular context.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells, are thought to be responsible for metastasis and chemoresistance.. In this study, based on whole transcriptome analysis from putative breast CSCs and reverse-engineering of transcription control networks, we were able to identify two networks associated to this phenotype.
Publication Title
Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype.
Sample Metadata Fields
Age, Disease stage
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of hindlimb muscles from dystrophic mice
Publication Title
Comparative transcriptome analysis of muscular dystrophy models Large(myd), Dmd(mdx)/Large(myd) and Dmd(mdx): what makes them different?
Sample Metadata Fields
Sex, Specimen part
View Samples