This SuperSeries is composed of the SubSeries listed below.
c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.
Cell line, Time
View SamplesProstate cancer is the most common non-cutaneous cancer in men. The androgen receptor (AR) a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signalling networks have been shown to be altered in patients and to influence AR activity. The oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies, but its impact on AR activity in prostate cancer remains elusive. In this study we assessed the impact of clinically relevant levels of c-Myc overexpression on AR activity and transcriptional output. We found that c-Myc and the AR share a substantial amount of binding sites, which exhibit enhancer-like characteristics. Interestingly, c-Myc overexpression altered global AR chromatin occupancy and antagonised a subset of androgen-induced genes. Furthermore, c-Myc overexpression modified histone marks, most notably H3K4me1 and H3K27me3. Lastly, we validated the antagonistic relationship between c-Myc and two AR target genes, KLK3 and GNMT, in patient samples.
c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.
Time
View SamplesIdentifying the functions of proteins, which define specific subnuclear structures and territories, is important for understanding eukaryotic nuclear dynamics. Sp100 is a prototypical protein of ND10/PML bodies and co-localizes with the proto-oncogenic protein PML and Daxx, proteins with critical roles in oncogenic transformation, interferon-mediated viral resistance and response to PML-directed cancer therapeutics. Sp100 isoforms contain PHD, Bromo and HMG domains and are highly sumoylated at ND10/PML bodies, all characteristics suggestive of a role in chromatin mediated gene regulation. However, no clear role for the Sp100 component of PML bodies in oncogenesis has been defined. Using isoform-specific knockdown techniques, we show that most human diploid fibroblasts, which lack Sp100, rapidly senesce and discuss gene expression changes associated with this rapid senescence.
Sp100 as a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program.
Cell line, Treatment
View SamplesLoss of Notch1 in retinal progenitor cells (RPCs) during postnatal retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia. To examine the molecular underpinnings of this observation, microarray analysis of singla retinal cells from wildtype (WT) or Notch1 conditional knockout (N1-CKO) retinas was performed. The majority of N1-CKO cells lost expression of known Notch target genes. These cells also had low levels of RPC and cell cycle genes, and robustly upregulated rod precursor genes. In addition, single WT cells, in which cell cycle marker genes were downregulated, expressed markers of both rod photoreceptors and interneurons. These results demonstrate that individual, newly postmitotic retinal cells can begin to differentiate into more than one cell type, and that this transitional state may be dependent on Notch1 signaling.
Notch1 is required in newly postmitotic cells to inhibit the rod photoreceptor fate.
Specimen part
View SamplesImpact of mmu-miR-337-3p on the global gene expression in murine hepatoblasts.
MicroRNA-337-3p controls hepatobiliary gene expression and transcriptional dynamics during hepatic cell differentiation.
Specimen part
View SamplesBackground: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed.
Marked alterations of neutrophil functions during sepsis-induced immunosuppression.
Disease
View SamplesSepsis is a major health concern, with high morbidity and mortality workdwide. In order to identify prognostic biomarkers in septic shock patients, we performed a microarray study exploring the early modulation of gene expression according to day 28 mortality.
Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation.
Sex, Age, Time
View SamplesRsp5 is an essential and multi-functional E3 ubiquitin ligase in Saccharomyces cerevisiae. We previously isolated the Ala401Glu rsp5 mutant, which is hypersensitive to various stresses. To understand the function of Rsp5 in stress responses, suppressor genes whose overexpression allows rsp5A401E cells to grow at high temperature were screened. The KIN28 and POG1 genes, encoding a subunit of the transcription factor TFIIH and a putative transcriptional activator, respectively, were identified as multicopy suppressors of not only high temperature but also LiCl stresses. The overexpression of Kin28 and Pog1 in rsp5A401E cells caused an increase in the transcriptional level of some stress proteins when exposed to temperature up-shift. DNA microarray analysis under LiCl stress revealed that the transcriptional level of some proteasome components was increased in rsp5A401E cells overexpressing Kin28 or Pog1. These results suggest that the overexpression of Kin28 and Pog1 enhances the protein refolding and degradation pathways in rsp5A401E cells.
Overexpression of two transcriptional factors, Kin28 and Pog1, suppresses the stress sensitivity caused by the rsp5 mutation in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesInducible overexpression of Arabidopsis meristem regulators by AlcR / AlcA system. Plants harboring 35S::AlcR/AlcA::GOI (GUS control, LEAFY, SHOOTMERSTEMLESS, WUSCHEL)constructs were grown in continous light for 12 days and induced with 1% Ethanol. After 12h of EtOH treatment, seedlings were dissected and RNA was processed from the shoot apex and young leaves. Affymetrix Ath1 arrays were hybridized in duplicates from each experiment.
WUSCHEL controls meristem function by direct regulation of cytokinin-inducible response regulators.
Age, Specimen part, Subject, Compound
View SamplesDensely ionizing radiation is a major component of the space radiation environment and has potentially greater carcinogenic effect compared to sparsely ionizing radiation that is prevalent in the terrestrial environment. It is unknown to what extent the irradiated microenvironment contributes to the differential carcinogenic potential of densely ionizing radiation. To address this gap, 10-week old BALB/c mice were irradiated with 100 cGy sparsely ionizing g-radiation or 10, 30, or 80 cGy of densely ionizing, 350 MeV/amu Si particles and transplanted 3 days later with syngeneic Trp53 null mammary fragments. Tumor appearance was monitored for 600 days. Tumors arising in Si-particle irradiated mice had a shorter median time to appearance, grew faster and were more likely to metastasize. Most tumors arising in sham-irradiated mice were ER-positive, pseudo-glandular and contained both basal keratin 14 and luminal keratin 8/18 cells (designated K14/18), while most tumors arising in irradiated hosts were K8/18 positive (designated K18) and ER negative. Comparison of K18 vs K14/18 tumor expression profiles showed that genes increased in K18 tumors were associated with ERBB2 and KRAS while decreased genes overlapped with those down regulated in metastasis and by loss of E-cadherin. Consistent with this, K18 tumors grew faster than K14/18 tumors and more mice with K18 tumors developed lung metastases compared to mice with K14/18 tumors. However, K18 tumors arising in Si-particle irradiated mice grew even faster and were more metastatic compared to control mice. A K18 Si-irradiated host profile was enriched in genes involved in mammary stem cells, stroma, and Notch signaling. Thus systemic responses to densely ionizing radiation enriches for a ER-negative, K18-positive tumor, whose biology is more aggressive compared to similar tumors arising in non-irradiated hosts.
Densely ionizing radiation acts via the microenvironment to promote aggressive Trp53-null mammary carcinomas.
No sample metadata fields
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