Although many genes have been proposed to be involved in prostate carcinogenesis, no single gene or gene profile has shown to have prognostic value. The main challenge for clinical management is to distinguish slowly growing tumors from those that will relapse. In this study, we compared expression profiles of 18 prostate samples (7 with Gleason 6, 8 with Gleason 7 and 3 with Gleason score equal or higher than 8) and 5 non-neoplastic prostate samples, using the GeneChip Human Exon Array 1.0 ST of Affymetrix. Microarray analysis revealed 99 genes showing statistically significant differences among tumors with Gleason score 6, 7 and 8. In addition, mRNA expression of 29 selected genes was analyzed by qRT-PCR with microfluidic cards in an extended series of 30 prostate tumors. From these, 29 were selected to be validated and the differential expression of 18 of them (62%) was independently confirmed by quantitative real-time RT-PCR (14 upregulated and 4 downregulated in higher Gleason scores) in the extended series. This list was further narrowed down to 12 genes that were differentially expressed in tumors with Gleason score of 6-7 vs 8. Finally, the protein levels of two genes from the 12-gene signature (SEC14L1 and TCEB1) were additionally validated by immunohistochemistry. Strong protein levels of both genes were correlated with Gleason score, stage, and PSA progression.
A 12-gene expression signature is associated with aggressive histological in prostate cancer: SEC14L1 and TCEB1 genes are potential markers of progression.
Specimen part
View SamplesComparative microarray-based transcriptome analysis of A. thaliana mlo2 mlo6 mlo12 mutants and wild type plants upon Golovinomyces orontii inoculation revealed an increased and accelerated accumulation of many defense-related transcripts. Despite the biotrophic nature of the interaction, this included the non-canonical activation of a jasmonic acid/ethylene-dependent transcriptional program.
Key Components of Different Plant Defense Pathways Are Dispensable for Powdery Mildew Resistance of the Arabidopsis <i>mlo2 mlo6 mlo12</i> Triple Mutant.
Specimen part, Treatment
View SamplesSeasonal influenza outbreaks and recurrent influenza pandemics present major challenges to public health. By studying immunological responses to influenza in different host species, it may be possible to discover common mechanisms of susceptibility in response to various influenza strains. This could lead to novel therapeutic targets with wide clinical application. Using a mouse-adapted strain of influenza (A/HK/1/68-MA20 [H3N2]), we produced a mouse model of severe influenza (p-flu) that reproduces the hallmark high viral load and overexpression of cytokines associated with susceptibility to p-flu in humans. We mapped genetic determinants of the host response using a panel of 29 closely related mouse strains (AcB/BcA panel of recombinant congenic strains) created from influenza-susceptible A/J and influenza-resistant C57BL/6J (B6) mice. Combined clinical quantitative trait loci (cQTL) and lung expression QTL (eQTL) mapping identified candidate genes for two sex-specific QTLs on chromosomes 2 and 17. The former includes the previously described Hc gene, a deficit of which is associated with the susceptibility phenotype in females. The latter includes the phospholipase gene Pla2g7 and Tnfrsf21, a member of the tumor necrosis factor receptor superfamily. Confirmation of the gene underlying the chromosome 17 QTL may reveal new strategies for influenza treatment.
Mapping of clinical and expression quantitative trait loci in a sex-dependent effect of host susceptibility to mouse-adapted influenza H3N2/HK/1/68.
Age, Specimen part
View SamplesEpidermal stem cells ensure proper faring of skin homeostatic processes under both physiological and challenging conditions. Currently, the molecular events underpinning ageing within the epidermal stem cell niche are poorly understood.
In Silico Analysis of the Age-Dependent Evolution of the Transcriptome of Mouse Skin Stem Cells.
Age, Specimen part
View SamplesWe analysed whole PolyA+ RNA from human osteosarcoma U2OS cells depleted for human Cactin or transfected with a control shRNA. Overall design: Two independent shRNAs targeting human Cactin (shCac_C and shCac_D), a control shRNA (shCtrl), a single cell line (U2OS)
Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion.
Cell line, Treatment, Subject, Time
View SamplesTo assess the effects of histone deacetylase (HDAC) inhibitor, HDACi 4b, treatment on muscle function on a molecular level, we performed microarray analysis on skeletal muscle (gastrocnemius) samples from wt and N17182Q mice treated with the HDAC inhibitor 4b for 3 months (50 mg/kg; s.c. injection 3x weekly; n=4 per group). The transcriptome pattern in N17182Q mice compared to wt controls consisted of deficits in the expression of genes related to mitochondrial function and oxidative metabolism. In addition, we noted that numerous genes associated with basal contractile function were altered in HD N17182Q mice. These include genes related to the muscle contractile complex, Tnnt3 and Myh8, as well as several additional myosin genes: myosin heavy chain genes, Myh10 and Myh4, and myosin light chain genes, Myl1, Mylc2 and Mylk. These findings implicate deficits in the underlying contractile function in skeletal muscle from HD mice. Further, we found robust effects of 4b treatment on the expression of genes in skeletal muscle, with 556 genes showing significantly altered expression, at p<0.005, in 4b-treated N17182Q muscle compared to vehicle-treated control mice.
HDAC inhibition imparts beneficial transgenerational effects in Huntington's disease mice via altered DNA and histone methylation.
Specimen part, Treatment
View SamplesThe importance of regulatory T cells (Treg) for immune tolerance is well recognized, yet the signaling molecules influencing their suppressive activity are relatively poorly understood. We identified the cytoplasmic tyrosine phosphatase SHP-1 as a novel endogenous brake and modifier of the suppressive ability of Treg cells; consistent with this notion, loss of SHP-1 expression strongly augments the ability of Treg cells to suppress inflammation in a mouse model. Specific harmacological inhibition of SHP-1 enzymatic activity via the cancer drug sodium stibogluconate (SSG) potently augmented Treg cell suppressor activity both in vivo and ex vivo.
The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells.
Specimen part
View SamplesAnoxia induces several heat shock proteins and a heat pre-treatment can acclimatize Arabidopsis seedlings to a subsequent anoxic treatment. In this work we analyzed the response of Arabidopsis seedlings to anoxia, heat and a combined heat+anoxia stress. A significant overlapping between the anoxic and heat shock responses has been observed by whole-genome microarray analysis.
The heat-inducible transcription factor HsfA2 enhances anoxia tolerance in Arabidopsis.
Age, Treatment
View SamplesArabidopsis thaliana ecotype Columbia glabra were grown for 4 days in the dark without added sucrose. Samples were subsequently kept for 6h either [1] under aerobic conditions, [2] under anoxia in absence of sucrose or [3] under anoxia in presence of sucrose.
A genome-wide analysis of the effects of sucrose on gene expression in Arabidopsis seedlings under anoxia.
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Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sex, Age, Specimen part, Treatment
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