In this study, the prognostic properties of miR-205 expression levels are investigated in a well-documented prostate cancer cohort. We show that miR-205 is correlated to shortened overall survival, significantly dividing the PCa patients into high and low risk groups. Furthermore, miR-205 is shown to inversely correlate to occurrence of metastases. In situ hybridization is also performed, demonstrating high miR-205 expression in the basal cells of benign prostate tissue glands. A RIP-Chip assay using an AGO2 antibody was implemented and the miR-205 targets identified were found to be enriched in MAPK/ERK, Toll-like receptor and IL-6 signaling pathways. We also found individual targets involved in cancer and androgen receptor signaling. Ectopic levels of miR-205 are shown to decrease the level of androgen receptor both at the mRNA and protein levels in prostate cancer cell lines. This is further corroborated in the prostate cancer cohort were miR-205 expression levels in the prostatic tissues are found to inversely correlate to assessment of androgen receptor (AR) immunostaining and to serum levels of PSA, a protein regulated by AR signaling. The level of miR-205 is also found to be significantly lower in castration resistant prostate cancer patients than in hormone nave patients. Our data indicates that miR-205 is regulated by androgens and act by different mechanisms in androgen depleted settings, e.g. giving opposite effects on adhesion. Taken together these findings imply that miR-205 might have therapeutic potential especially for the castration resistant and currently untreatable form of prostate cancer.
miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients.
Specimen part, Cell line
View SamplesOBJECTIVE: Previous expression microarray analyses have failed to take into consideration the genetic heterogeneity and complex patterns of ERG gene alteration frequently found in cancerous prostates. The objective of this study is for the first time, to integrate the mapping of ERG gene alterations with the collection of expression microarray data.
Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer.
Sex, Specimen part
View SamplesGene expression of P. aerruginosa changes after short-term exposure to ciprofloxacin at sub-inhibitory concentrations but the effect of long-term exposure which select for the most fitted subpopulations is not known.
The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin.
No sample metadata fields
View SamplesIn the present in vitro study, interactions between P. aeruginosa (sessile biofilms as well as planktonic cells) and PMNs were analyzed by means of DNA microarray based transcriptomics. We found that the P. aeruginosa wild type biofilms, in contrast to planktonic cultures and quorum sensing (QS) deficient strains, respond to PMN exposure in a rather aggressive manner. The response does not involve protective mechanisms such as those involved in oxidative stress. Rather it is dominated by QS controlled virulence determinants such as those encoded by pqs, phz, rhlAB, all of which are designed to cripple Eukaryotic cells including PMNs and macrophages. Our comparative analysis supports the view that QS plays a major role in mechanisms by which P. aeruginosa evades host defense systems.
Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes.
No sample metadata fields
View SamplesTranscriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on day 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-gamma-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection.
Genome-wide transcription profile of endothelial cells after cardiac transplantation in the rat.
Sex, Specimen part
View Samples