Despite widespread knowledge that bone marrow-resident breast cancer cells (BMRCs) affect tumor progression, signaling mechanisms of BMRCs implicated in maintaining long-term dormancy have not been characterized. To overcome these hurdles, we developed a novel experimental model of tumor dormancy employing circulating tumor cells (CTCs) derived from metastatic breast cancer patients (de novo CTCs), transplanted them in immunocompromised mice, and re-isolated these cells from xenografted mice bone marrow (ex vivo BMRCs) and blood (ex vivo CTCs) to perform downstream transcriptomic analyses.
Molecular Interplay between Dormant Bone Marrow-Resident Cells (BMRCs) and CTCs in Breast Cancer.
Sex, Specimen part, Disease stage
View SamplesTo investigate the time-dependent and coordinated sequence of inflammation-related events, and the dynamic features of macrophage polarisation/activation, we build and validated an in vitro model based on primary human monocytes
Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro.
Specimen part
View SamplesRice transgenic plants of the F-box encoding gene, OsFBK1, in the Pusa Basmati 1 (PB1) variety have been found to display differences in the anther and root phenotypes. In order to elucidate changes at the transcriptome level, microarray of the roots of 14-day-old seedlings of over-expresseion (OE) and knock-down (KD) lines along with vector control (VC) and wild type (WT) were carried out.
The OsFBK1 E3 Ligase Subunit Affects Anther and Root Secondary Cell Wall Thickenings by Mediating Turnover of a Cinnamoyl-CoA Reductase.
Specimen part
View SamplesT4 and T5 neurons are components of the neuronal circuit for motion vision in flies. To identify genes involved in neuronal computation of T4 and T5 neurons, we perfomed transcriptome analysis. Nuclei of T4 and T5 neurons were immunoprecipitated, total RNA was harvested and used for mRNA-seq with Illumina technology. In two biological replicates, we mapped 154 and 119 million reads to D. melanogaster genome. mRNA-seq provided information about expression levels of 17,468 annotated transcripts in the T4 and T5 neurons. Overall design: Cell type – specific transcriptome analysis of the RNA isolated from immunoprecipitated nuclei, performed in two biological replicates
RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila.
Subject
View SamplesThe enumeration of EpCAM-positive circulating tumor cells (CTCs) has allowed clinicians to estimate the overall metastatic burden in breast cancer patients. However, a thorough understanding of CTCs associated with breast cancer brain metastasis (BCBM) is necessary for early identification and evaluation of treatment response to BCBM. In this study, we report that BCBM CTCs are enriched in a distinct sub-population of cells identifiable by their biomarker expression and mutational content.
Molecular characterization of breast cancer CTCs associated with brain metastasis.
Sex
View SamplesThe activation of endothelium by tumor cells is one of the main steps by tumor metastasis. The role of the blood components (platelets and leukocytes) in this process remain unclear.
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
Specimen part
View SamplesElevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches, we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition.
Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer.
No sample metadata fields
View SamplesElevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches, we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition.
Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer.
No sample metadata fields
View SamplesThe ubiquitous efflux transporter ATP-binding cassette sub-family C member 5 (ABCC5) is present at high levels in the blood-brain barrier, neurons and glia, but its in vivo substrates and function are not known. Untargeted metabolomic screens revealed that Abcc5-/- mice accumulate endogenous glutamate conjugates and analogs in several tissues, but brain in particular. The abundant neurotransmitter N-acetylaspartylglutamate (NAAG), for example, was over 2-fold higher in Abcc5-/- brain. In line with ABCC5-mediated transport, the metabolites that accumulated in Abcc5-/- tissues were depleted in cultured cells that overexpressed human ABCC5. Using membrane vesicles, we show that ABCC5 not only transports the metabolites detected in our screen, but also a wide range of peptides containing a C-terminal glutamate. Glutamate conjugates are of physiological relevance because they can affect the function of glutamate, the principal excitatory neurotransmitter in the brain. We found that ABCC5 also transports exogenous glutamate analogs, like the classic excitotoxic neurotoxins kainic acid, domoic acid and N-methyl-D-aspartate (NMDA) and the therapeutic glutamate analog ZJ43. Taken together, we have identified ABCC5 as a general glutamate conjugate and analog transporter that affects the disposition of endogenous metabolites, toxins and drugs. Overall design: A set of 5 wildtype brains was compared to a set of 5 Abcc5-knockout mouse brains
ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux Transporter of Glutamate Conjugates and Analogs.
No sample metadata fields
View SamplesThe genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, that included expression of mRNAs regulated by either transforming growth factor, beta 1 (TGFB1) pathways or microphthalmia-associated transcription factor (MITF)/SRY-box containing gene 10 (SOX10) pathways. We extend this knowledge to include gene expression analyses of 5 additional human melanoma lines, and show that these lines also fall into either TGFB1 or MITF/SOX10 gene expression groups.
Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A.
Cell line
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