Genetically engineered mouse models of cancer represent valuable biological tools that can be used to filter genome-wide expression datasets generated from human prostate tumours, and identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNASeq data from tumours arising in two established mouse models of prostate cancer, PB-Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer-associated gene expression changes that are conserved between the two species. In order to identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we identified the serine/threonine kinase MELK as a potential therapeutic target in prostate cancer. MELK was overexpressed in both human and murine prostate cancers, and high expression of MELK was associated with biochemical recurrence in prostate cancer patients. Overall design: 92 Samples
Identification of potential therapeutic targets in prostate cancer through a cross-species approach.
Cell line, Subject
View SamplesCastrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance in early prostate cancer, other factors such as c-Myc and the E2F family also play a role in later stage disease. Hes6 is a transcription co-factor that has been associated with neurogenesis during gastrulation, a neuroendocrine phenotype in the prostate and metastasis in breast cancer but its role in prostate cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and AR and drives castration resistance in prostate cancer. Hes6 activates a cell-cycle enhancing transcriptional network that maintains tumour growth and nuclear AR localization in castrate conditions. We show aphysical interaction between E2F1 and both Hes6 and AR, and suggest a co-dependency of these transcription factors in castration-resistance. In the clinical setting, we have uncovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted. We have therefore shown for the first time the critical role of Hes6 in the development of CRPC and identified its potential in patient specific therapeutic strategies.
HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.
Specimen part, Disease, Cell line
View SamplesHes6 is a transcription co-factor that is associated with stem cell characteristics in neural tissue, but its role in cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and the AR and can drive castration resistance in xenografts of the androgen-dependent LNCaP prostate cancer cell line model. Hes6 activates a cell cycle enhancing transcriptional network that maintains tumour growth in the absence of circulating androgen but with maintained nuclear AR. We demonstrate interaction between E2F1, the AR and Hes6 and show the co-dependency of these factors in the castration-resistant setting. In the clinical setting, we have discovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which could be pharmacologically targeted.
HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.
Cell line
View SamplesThe comparative advantages of RNA-Seq and microarrays in transcriptome profiling were evaluated in the context of a comprehensive study design. Gene expression data from Illumina RNA-Seq and Affymetrix microarrays were obtained from livers of rats exposed to 27 agents that comprised of seven modes of action (MOAs); they were split into training and test sets and verified with real time PCR.
The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.
Sex, Specimen part
View SamplesActivation of inflammatory pathways in human IBD
Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease.
No sample metadata fields
View SamplesWe investigated the differential regulation patterns of type I anti-CD20 monoclonal antibody (mAb) rituximab and type II obinutuzumab on a transcriptional level. Using a panel of MCL cell lines, we determined the effects of obinutuzumab and rituximab as monotherapies as well as in combination on cell viability and proliferation.
Differential regulation patterns of the anti-CD20 antibodies obinutuzumab and rituximab in mantle cell lymphoma.
Specimen part, Cell line
View SamplesTo validate the suitability of two commonly used colorectal cancer cell lines, DLD1 and SW480, as model systems to study colorectal carcinogenesis, we treated these cell lines with -catenin siRNA and identified -catenin target genes using DNA microarrays. The list of identified target genes was compared to previously published -catenin target genes found in the PubMed and the GEO databases.
Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling.
Cell line, Treatment
View SamplesPurpose: The diagnosis of high grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low grade IPMN. The aim of this study was to identify potential markers for the discrimination of high grade and invasive IPMN from low and moderate grade IPMN.
Gene expression changes associated with the progression of intraductal papillary mucinous neoplasms.
Disease, Disease stage, Subject
View SamplesThe goals of this study were to determine global differences in transcript expression and regulation between MM cells that are sensitive or insensitive to lovastatin-induced apoptosis. To this end, two sensitive (KMS11 and H929) and two insensitive (LP1 and SKMM1) MM cell lines treated with 20uM lovastatin or an ethanol vehicle control for 16 hours. mRNA was extracted and prepared for mRNA expression microarrays (HG-U133 Plus 2) in triplicate.
Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma.
Specimen part, Cell line, Treatment
View SamplesTissue-resident mononuclear phagocytes (MNPs) in metabolic organs contribute to the regulation of whole body metabolism. CD301b+ MNPs are a subset of MNPs that are found in most peripheral organs including metabolic organs. In a mouse model in which CD301b+ MNPs can be selectively and transiently depleted, we examined the impact of the depletion on gene expression in the white adipose tissue and the liver.
CD301b(+) Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha.
Specimen part
View Samples