The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The human mammary gland contains two distinctive types of fibroblasts within the stroma. The epithelial cells are surrounded by loosely connected intralobular fibroblasts, which are subsequently surrounded by the more compacted interlobular fibroblasts. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. In this report, we compared the gene expression profiles between the two stromal subtypes.
Interlobular and intralobular mammary stroma: genotype may not reflect phenotype.
No sample metadata fields
View SamplesGenome-wide gene expression in 33 fusion-positive and 25 fusion-negative rhabdomyosarcoma cases was studied using GeneChip Human Genome U133 Plus2 (Affymetrix)
Distinct methylation profiles characterize fusion-positive and fusion-negative rhabdomyosarcoma.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.
Specimen part, Cell line, Treatment
View SamplesEWS-FLI1 is a chimeric ETS transcription factor that is, due to a chromosomal rearrangement, specifically expressed in Ewings sarcoma family tumors (ESFT) and is thought to be the initiating event in the development of the disease. Previous genomic profiling experiments have identified a number of EWS-FLI1 regulated genes and genes that discriminate ESFT from other sarcomas, but so far a comprehensive analysis of EWS-FLI1 dependent molecular functions characterizing this aggressive cancer is lacking. In this study a molecular function map of ESFT was constructed based on an integrative analysis of gene expression profiling experiments on a uniform microarray platform following EWS-FLI1 knockdown in a panel of five ESFT cell lines, and on gene expression data from the same platform of 59 primary ESFT tumors. Based on the assumption that EWS-FLI1 is the driving transcriptional force in ESFT pathogenesis, we predicted an inverse correlation of gene expression for EWS-FLI1 regulated genes between the putative tissue of origin and the cell lines under EWS-FLI1 knockdown conditions. Consistent with recent reports, mesenchymal progenitor cells (MPC) were found to fit this hypothesis best and were therefore used as the reference tissue for the construction of the molecular function map in ESFT.
A molecular function map of Ewing's sarcoma.
No sample metadata fields
View SamplesHuman HOS cell line was differentiated by beta-glycerophosphate (BGP) treatment and gene expression profiling was studied with Illumina expression microarray (HumanHT12_V4).
miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.
Specimen part, Cell line, Treatment
View SamplesHuman HOS cell line was overexpressed with miR23a and gene expression profiling was studied with Illumina expression microarray (HumanHT12_V4).
miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.
Specimen part, Cell line
View SamplesIn fasted mammals, glucose homeostasis is maintained through activation of the cAMP responsive CREB coactivator TORC2, which stimulates the gluconeogenic program in concert with the forkhead transcription factor FOXO1. Here we show that starvation also triggers TORC activation in Drosophila, where it maintains energy balance by promoting the expression of CREB target genes in the brain. TORC mutant flies have reduced glycogen and lipid stores, and they are sensitive to starvation as well as oxidative stress. Neuronal TORC expression rescued starvation and oxidative stress sensitivity as well as CREB target gene expression in TORC mutants. During refeeding, increases in insulin signaling inhibited TORC activity in wild type flies by stimulating the Salt Inducible Kinase 2 (SIK2)-mediated phosphorylation and subsequent degradation of TORC. Depletion of neuronal SIK2 increased TORC activity and enhanced resistance to starvation and oxidative stress in adult flies. As disruption of insulin signaling, either by ablation of insulin-producing cells (IPCs) or by mutation of the insulin receptor adaptor gene chico, also increased TORC activity, our results illustrate the importance of an insulin-regulated pathway in brain that promotes energy balance in Drosophila.
The insulin-regulated CREB coactivator TORC promotes stress resistance in Drosophila.
No sample metadata fields
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
No sample metadata fields
View SamplesIdiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease that is difficult to diagnose and follows an unpredictable clinical course. The object of this study was to develop a predictive gene signature model of IPF from whole lung tissue. We collected whole lung samples from 11 IPF patients undergoing diagnostic surgical biopsy or transplantation. Whenever possible, samples were obtained from different lobes. Normals consisted of healthy organs donated for transplantation. We measured gene expression on microarrays. Data were analyzed by hierarchical clustering and Principal Component Analysis. By this approach, we found that gene expression was similar in the upper and lower lobes of individuals with IPF. We also found that biopsied and explanted specimens contained different patterns of gene expression; therefore, we analyzed biopsies and explants separately. Signatures were derived by fitting top genes to a Bayesian probit regression model. We developed a 153-gene signature that discriminates IPF biopsies from normal. We also developed a 70-gene signature that discriminates IPF explants from normal. Both signatures were validated on an independent cohort. The IPF Biopsy signature correctly diagnosed 76% of the validation cases (p < 0.01), while IPF Explant correctly diagnosed 78% (p < 0.001). Examination of differentially expressed genes revealed partial overlap between IPF Biopsy and IPF Explant and almost no overlap with previously reported IPF gene lists. However, several overlapping genes may provide a basis for developing therapeutic targets.
Bayesian probit regression model for the diagnosis of pulmonary fibrosis: proof-of-principle.
Sex, Age, Specimen part
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
Specimen part, Disease, Disease stage, Cell line
View Samples