Disseminated prostate cancer cells colonize the skeleton to progress into macroscopic lesions only if they successfully adapt to the bone microenvironment. We previously reported that the ability of prostate cancer cells to generate skeletal tumors in animal models correlated with the expression of the alpha-receptor for Platelet-Derived Growth Factor (PDGFRa). In this study we aimed to identify PDGFRa-regulated genes responsible for the acquisition of a bone-metastatic prostate phenotype. We performed genome-wide expression comparative analyses of human prostate cancer cell lines that differ for PDGFRa expression and propensity to establish tumors in the skeleton of animal models. We investigated the genes that were differentially regulated in the highly bone-metastatic PC3-ML cells and their low-metastatic counterpart PC3-N cells, and the genes differentially regulated between PC3-N and PC3-N with overexpression of PDGFRa (PC3NRa). We have previously shown that DU-145 cells lack PDGFRa and fail to survive longer than three days as disseminated tumor cells after homing to the mouse bone marrow. Interestingly, and in contrast to PC3-N cells, the exogenous expression of PDGFRa did not promote metastatic bone-tropism of DU-145 cells in our model. Thus, we examined the genes that were differentially regulated between DU-145 and DU-145(Ra) and excluded them from our candidate genes. Finally, to refine our findings and compensate for PC3 and DU-145 genetic disparity, we performed a comparative analysis of the genes differentially regulated between two bone metastatic single-cell progenies that were derived from PC3-ML cells.
Interleukin-1β promotes skeletal colonization and progression of metastatic prostate cancer cells with neuroendocrine features.
Cell line
View SamplesCyclin D1b is a splice variant of the cell cycle regulator Cyclin D1 and is known to harbor divergent and highly oncogenic functions in human disease. While Cyclin D1b is induced during disease progression in many cancer types, the mechanisms underlying Cyclin D1b function remain poorly understood. Herein, models of human disease were utilized to resolve the downstream pathways requisite for the pro-tumorigenic functions of Cyclin D1b. Specifically, it was shown that Cyclin D1b modulates the expression of a large transcriptional network that cooperates with AR signaling to enhance tumor cell growth and invasive potential. Notably, Cyclin D1b promoted AR-dependent activation of genes associated with metastatic phenotypes. Further exploration determined that transcriptional induction of SNAI2 (Slug) was essential for Cyclin D1b- mediated proliferative and invasive properties, implicating Slug as a critical driver of disease progression. Importantly, Cyclin D1b expression highly correlated with that of Slug in clinical samples of advanced disease. Further, in vivo analyses provided strong evidence that Slug enhances both tumor growth and homing to distal soft tissues. Collectively, these findings reveal the underpinning mechanisms behind the pro-tumorigenic functions of Cyclin D1b, and demonstrate that the convergence of the Cyclin D1b-AR and Slug pathways results in the activation of processes critical for the promotion of lethal tumor phenotypes.
Convergence of oncogenic and hormone receptor pathways promotes metastatic phenotypes.
Specimen part, Cell line
View SamplesIntact living conduit vessels (umbilical veins) were exposed to normal or high intraluminal pressure, or low or high shear stress in combination with a physiological level of the other force. We used a unique vascular ex vivo perfusion system. After six hours of perfusion endothelial cells were isolated from the stimulated vessels and RNA was extracted. RNA from 16 experiments from each stimulation were pooled and analyzed in duplicate DNA microarrays.
Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressure.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP).
No sample metadata fields
View SamplesMicroRNA are small non-coding RNA molecules that regulate gene expression. To investigate the role of microRNA in ITP, we performed genome-wide expression analyses of mRNA and microRNA in T-cells from ITP patients and controls. We identified 1,915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, e.g. T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of IL-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP.
MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP).
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA regulate immune pathways in T-cells in multiple sclerosis (MS).
Specimen part, Disease, Disease stage
View SamplesMicroRNAs are small noncoding RNA molecules that are involved in the control of gene expression. To investigate the role of microRNA in multiple sclerosis (MS), we performed global microarray analyses of mRNA and microRNA in peripheral blood T-cells from relapsing-remitting MS patients and controls. We identified 2,452 regulated genes and 21 regulated microRNA that differed between MS patients and controls. By Kolmogorov-Smirnov test, 20 of 21 regulated microRNA were shown to affect the expression of their target genes, many of which are involved in the immune system. LIGHT (TNFSF14) was a microRNA target gene significantly decreased in MS. The down-regulation of mir-494 and predicted mRNA-target LIGHT was verified by real-time PCR and we could demonstrate decreased serum levels of LIGHT in MS. Thus, regulated microRNA were significantly associated with both gene and protein expression of a molecule in immunological pathways. These findings indicate that microRNA may be important regulatory molecules in T-cells in MS.
MicroRNA regulate immune pathways in T-cells in multiple sclerosis (MS).
Specimen part, Disease, Disease stage
View SamplesDifferent human adipose tissue depots may have functional differences. Subcutaneous human adipose tissue has been extensively studied, but less is known about other depots. Perithyroid (PT) adipose tissue contains not only white adipocytes but also brown adipocytes. The aim of this study was to compare the expression of brown adipocyte containing perithyroid adipose tissue with s.c. adipose tissue.role in the development of obesity. Expression profiling of adipose tissue may give insights into mechanisms contributing to obesity and obesity-related disorders.
Gene expression in human brown adipose tissue.
Sex, Specimen part
View SamplesChildren with newly diagnosed ITP that after 12 month enter remission, shows molecular separate entities. The molecular basis for remission and tolerance induction is characterized by gene transcriptional profiling
Normalised immune expression in remission of paediatric ITP.
No sample metadata fields
View SamplesThe aim of this study was to find disease-associated genes in atopic eczema.
Increased expression of aquaporin 3 in atopic eczema.
No sample metadata fields
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