Filters
Technology
Platform
GSE21656
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Combination of platinum-based chemotherapy and radiation is currently the standard treatment for locally advanced lung cancer patients. However, therapeutic resistance to these therapies may arise from the presence of cancer stem cells (CSCs). To investigate the CSCs hypothesis of chemo-radiation resistance, we used microarray assay to profile CSCs-like cisplatin-resistant lung cancer cells (CDDP-R) versus its parental cells. CDDP-R cells were established by exposing H460 lung cancer cells to 3M cisplatin for 7 days, followed by 0.8% methylcellulose selection over 14 consecutive days.We found that CDDP-R cells expressed higher levels of stem cell markers, including CD133 and ALDH. They are more resistant to cisplatin- and etoposide-induced apoptosis and to high radiation dose (20Gy). Clonogenic assays suggest that CDDP-R cells were more resistant to radiation than parental H460 cells (DER=1.21, p<0.01). Xenograft studies suggest that CDDP-R cells were more tumorigenic (p<0.001). Microarray and comprehensive protein interaction networks analyses revealed IGFBP3 as a highly ranked hub protein which plays an important role in the mechanism of cisplatin resistance. We found reduced level of IGFBP3 and enhanced IGFR-1 activation upon IGF stimulation in CDDP-R cells. The specific targeting of IGF-1R using siRNA resulted in significant sensitization of CDDP-cells (DER=1.17, p<0.05) to radiation compared with the parental H460 cells. Our findings suggest that CDDP-R cells have the characteristics of CSCs and constitute a suitable model to study lung CSCs. Profiling of CSCs-like H460 cells led to the identification of IGF as an important pathway for chemo- and radiotherapy resistance in lung cancer.
Publication Title
Role of insulin-like growth factor-1 signaling pathway in cisplatin-resistant lung cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
Sentrix MouseRef-8 Expression BeadChip (Target ID), Rosetta/Merck Mouse TOE 75k Array 1 microarray
Description
A major task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription, and phenotypic information. Here we validated our method through the characterization of transgenic and knockout mouse models of candidate genes that were predicted to be causal for abdominal obesity. Perturbation of eight out of the nine genes, with Gas7, Me1 and Gpx3 being novel, resulted in significant changes in obesity related traits. Liver expression signatures revealed alterations in common metabolic pathways and networks contributing to abdominal obesity and overlapped with a macrophage-enriched metabolic network module that is highly associated with metabolic traits in mice and humans. Integration of gene expression in the design and analysis of traditional F2 intercross studies allows high confidence prediction of causal genes, and identification of involved pathways and networks.
Publication Title
Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Sentrix MouseRef-8 Expression BeadChip (Target ID)
Description
A major task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription, and phenotypic information. Here we validated our method through the characterization of transgenic and knockout mouse models of candidate genes that were predicted to be causal for abdominal obesity. Perturbation of eight out of the nine genes, with Gas7, Me1 and Gpx3 being novel, resulted in significant changes in obesity related traits. Liver expression signatures revealed alterations in common metabolic pathways and networks contributing to abdominal obesity and overlapped with a macrophage-enriched metabolic network module that is highly associated with metabolic traits in mice and humans. Integration of gene expression in the design and analysis of traditional F2 intercross studies allows high confidence prediction of causal genes, and identification of involved pathways and networks.
Publication Title
Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Sentrix MouseRef-8 Expression BeadChip (Target ID)
Description
A major task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription, and phenotypic information. Here we validated our method through the characterization of transgenic and knockout mouse models of candidate genes that were predicted to be causal for abdominal obesity. Perturbation of eight out of the nine genes, with Gas7, Me1 and Gpx3 being novel, resulted in significant changes in obesity related traits. Liver expression signatures revealed alterations in common metabolic pathways and networks contributing to abdominal obesity and overlapped with a macrophage-enriched metabolic network module that is highly associated with metabolic traits in mice and humans. Integration of gene expression in the design and analysis of traditional F2 intercross studies allows high confidence prediction of causal genes, and identification of involved pathways and networks.
Publication Title
Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Sentrix MouseRef-8 Expression BeadChip (Target ID)
Description
A major task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription, and phenotypic information. Here we validated our method through the characterization of transgenic and knockout mouse models of candidate genes that were predicted to be causal for abdominal obesity. Perturbation of eight out of the nine genes, with Gas7, Me1 and Gpx3 being novel, resulted in significant changes in obesity related traits. Liver expression signatures revealed alterations in common metabolic pathways and networks contributing to abdominal obesity and overlapped with a macrophage-enriched metabolic network module that is highly associated with metabolic traits in mice and humans. Integration of gene expression in the design and analysis of traditional F2 intercross studies allows high confidence prediction of causal genes, and identification of involved pathways and networks.
Publication Title
Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Sentrix MouseRef-8 Expression BeadChip (Target ID)
Description
A major task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription, and phenotypic information. Here we validated our method through the characterization of transgenic and knockout mouse models of candidate genes that were predicted to be causal for abdominal obesity. Perturbation of eight out of the nine genes, with Gas7, Me1 and Gpx3 being novel, resulted in significant changes in obesity related traits. Liver expression signatures revealed alterations in common metabolic pathways and networks contributing to abdominal obesity and overlapped with a macrophage-enriched metabolic network module that is highly associated with metabolic traits in mice and humans. Integration of gene expression in the design and analysis of traditional F2 intercross studies allows high confidence prediction of causal genes, and identification of involved pathways and networks.
Publication Title
Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 424 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Background: Obesity is a risk factor for breast cancer in postmenopausal women and is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, molecular mechanisms through which excess adiposity influences breast cancer etiology are not well-defined.
Publication Title
Effect of obesity on molecular characteristics of invasive breast tumors: gene expression analysis in a large cohort of female patients.
Sample Metadata Fields
Disease stage
View Samples- Rattus norvegicus
- 20 Downloadable Samples
Illumina HiSeq 2500
Description
Gene expression analysis of hypothalami from female animals at different juvenile developmental reproductive stages. Results provide insight into the role of the hypothalamus in controlling the onset of puberty. Overall design: SD rats were housed (8/cage) in a controlled environment and euthanized at different ages (PND=7, PND=14, Early Juvenile: 21 days, Late Juvenile: 28 days, Late Proestus (the day of first ovulation): 30-33 days. Rats were anesthetized and brains were rapidly removed. The medial basal hypothalamus (MBH) was dissected away from the rest of the brain and flash frozen. Total RNA was isolated from each sample using Qiagen''s RNeasy Mini Kit (Valencia, CA). Samples were bioanalyzed on a RNA 6000 Nano chip kit to check for integrity and concentration before sending it to OHSU''s Massively Parallel Sequencing Shared Resource for library preparation and sequencing.
Publication Title
Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The hematopoietic microenvironment consists of non-hematopoietic derived stromal elements and hematopoietic derived monocytes and macrophages which interact and function together to control the proliferation and differentiation of early blood-forming cells. Two human stromal cell lines (HS-5 and HS-27a) representing distinct functional components of this microenvironment have been extensively characterized and shown to influence monocyte gene expression. This series of gene expression profiles is intended to extend the previous studies and identify which gene expression changes may require cell-cell contact or occur in the stromal cells as a result of monocyte influence;or in the monocytes as a result of stormal influences.
Publication Title
Functionally and phenotypically distinct subpopulations of marrow stromal cells are fibroblast in origin and induce different fates in peripheral blood monocytes.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The bone marrow microenvironment is a complex mixture of cells that function in concert to regulate hematopoiesis. Cellular components include fixed nonhematopoietic stromal elements as well as monocytes and resident macrophages, which are derived from the hematopoietic stem cells. Although these monocyte-lineage cells are reported to modify stromal cell function, the reverse also occurs. Given the secretory capability of the monocyte/macrophage and their various potential functions, it is not surprising that stromal cells contained within a particular niche can modify monocyte gene expression and functional maturation.
Publication Title
Functionally and phenotypically distinct subpopulations of marrow stromal cells are fibroblast in origin and induce different fates in peripheral blood monocytes.
Sample Metadata Fields
Sex
View Samples