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GSE88935
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Differentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different transcription factors (TFs). A disturbed function of TFs can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Growth Factor Independence 1b (Gfi1b) is a repressing TF with a key role in quiescence of HSCs and emergence and maturation of erythrocytes and platelets. Here, we show that low expression of GFI1B in blast cells is associated with inferior prognosis of MDS and AML patients. Using mouse models with either reduced expression or conditional deletion of Gfi1b, crossed with a mouse model reflecting human MDS or AML, we demonstrate that AML development was accelerated with heterozygous loss of Gfi1b, and latency was further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b significantly enhanced stemness of leukemic cells with upregulation of genes fundamentally involved in leukemia development. On a molecular level, we found that loss of Gfi1b not only increased the levels of reactive oxygen species (ROS) but also induced gene expression changes of key AML pathways such as the p38/AKT pathway. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS/AML development.
Publication Title
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
One of the most important features of tumor microenvironment, imposing adverse effect on patient prognosis, is low oxygen tension. There are two types of hypoxia that may occur within tumor mass: chronic and cycling. Preliminary studies point at cycling hypoxia as being more relevant in induction of aggressive phenotype of tumor cells and radioresistance though little is known about the molecular mechanism of this phenomenon. Analysis of gene expression profile of human prostate (PC-3), ovarian (SK-OV-3) and melanoma (WM793B) cancer cells to expermental cycling (interchanging conditions of 1% and 21% oxygen) or chronic (1% oxygen) for 72 hours. Gene expression profiles were analyzed using U133 Plus 2.0 Array (Affymetrix) oligonucleotide microarrays. Data analysis revealed that globally gene expression profiles induced by the two types of hypoxia are similar and they strongly depend on the cell type.However, cycling hypoxia changes expression of lower number of genes in comparison to chronic one ( 3767 vs. 5954 probesets (p<0.001)) and to lower extent (lower fold changes). Analysis of hypoxia-regulated gene lists obtained using Random Variance Model t-test identified 253 probe sets (FC>2, p<0.001) common to all three cell lines, though no universal (changed throughout all analyzed cell lines) genes specifically influanced only by cycling hypoxia was selected. On the other hand, we identified such genes within particular one or two cell lines. Among them those related with EGF pathway seemed to be overrepresented (i.e. EPHA2, AREG, and HBEGF) and together with PLAU and IL-8 were mostly validated by Q-PCR.
Publication Title
Global gene expression profiling in three tumor cell lines subjected to experimental cycling and chronic hypoxia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Analysis of gene expression profile of B16-F10 murine melanoma cells exposed to hypoxic conditions (1% oxygen) or hypoxia mimicry (cobalt chloride) for 24 hours. Gene expression profiles were analyzed using MG-U74Av2 oligonucleotide microarrays. Data analysis revealed 2541 probesets (FDR<5%) for 1% oxygen experiment and 364 probesets (FDR<5%) for cobalt chloride, that showed differences in expression levels. Analysis of hypoxia-regulated genes (1% O2) by stringent Family-Wise Error Rate estimation indicated 454 significantly changed transcripts (p<0.05). The most upregulated genes were Lgals3, Selenbp1, Nppb (more than ten-fold increase). Both hypoxia and hypoxia-mimicry induced HIF-1 regulated genes. However, unsupervised analysis (Singular Value Decomposition) revealed distinct differences between gene expression induced by these two experimental conditions.
Publication Title
Gene expression profile of B 16(F10) murine melanoma cells exposed to hypoxic conditions in vitro.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In somatic cells elevated temperature induces activation of the heat shock transcription factor 1 (HSF1) what leads to heat shock proteins synthesis and cytoprotection. However, in the male germ cells (spermatocytes) upon HSF1 activation, caspase-3 dependent apoptosis is induced and spermatogenic cells are actively eliminated.
Publication Title
Impact of heat shock transcription factor 1 on global gene expression profiles in cells which induce either cytoprotective or pro-apoptotic response following hyperthermia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Mutation of MTF in Arabidopsis increases Agrobacterium-mediated transformation susceptibility. Being a putative transcription factor, different genes controlling transformation may be regulated by MTF.
Publication Title
Cytokinins secreted by Agrobacterium promote transformation by repressing a plant myb transcription factor.
Sample Metadata Fields
Specimen part
View Samples- Ovis aries
- 43 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Lambs that inherit a callipyge allele from their dam have an up-regulation of maternally imprinted transcripts near the callipyge mutation but do not exhibit muscle hypertrophy. It is not clear what effects these maternally expressed transcripts have in the muscle or how the inheritance of a maternal callipyge allele prevents the expression of the callipyge phenotype which is seen paternal heterozygotes only.
Publication Title
Effect of DLK1 and RTL1 but not MEG3 or MEG8 on muscle gene expression in Callipyge lambs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 99 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The introduction of microarray techniques to cancer research brought great expectations for finding biomarkers that would improve patients treatment; however, the results of such studies are poorly reproducible and critical analyses of these methods are rare. In this study, we examined global gene expression in 97 ovarian cancer samples. Also, validation of results by quantitative RT-PCR was performed on 30 additional ovarian cancer samples. We carried out a number of systematic analyses in relation to several defined clinicopathological features. The main goal of our study was to delineate the molecular background of ovarian cancer chemoresistance and find biomarkers suitable for prediction of patients prognosis. We found that histological tumor type was the major source of variability in genes expression, except for serous and undifferentiated tumors that showed nearly identical profiles. Analysis of clinical endpoints [tumor response to chemotherapy, overall survival, disease-free survival (DFS)] brought results that were not confirmed by validation either on the same group or on the independent group of patients. CLASP1 was the only gene that was found to be important for DFS in the independent group, whereas in the preceding experiments it showed associations with other clinical endpoints and with BRCA1 gene mutation; thus, it may be worthy of further testing. Our results confirm that histological tumor type may be a strong confounding factor and we conclude that gene expression studies of ovarian carcinomas should be performed on histologically homogeneous groups. Among the reasons of poor reproducibility of statistical results may be the fact that despite relatively large patients group, in some analyses one has to compare small and unequal classes of samples. In addition, arbitrarily performed division of samples into classes compared may not always reflect their true biological diversity. And finally, we think that clinical endpoints of the tumor probably depend on subtle changes in many and, possibly, alternative molecular pathways, and such changes may be difficult to demonstrate.
Publication Title
Gene expression analysis in ovarian cancer - faults and hints from DNA microarray study.
Sample Metadata Fields
No sample metadata fields
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