Pathologic and epidemiologic evidence has led to a histologic model of breast cancer progression that involves advancement through specific morphologic stages including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (IMC), although not necessarily always in a linear fashion. Numerous observational studies have examined genetic, epigenetic and gene expression differences in breast tissues representing these different stages of progression, but model systems which would allow for experimental testing of specific factors influencing transition through these stages are scarce. The 21T series cell lines, all originally derived from the same patient with metastatic breast cancer, have been proposed to represent a mammary tumor progression series. We report here that three of the 21T cell lines indeed mimic specific stages of human breast cancer progression (21PT-derived cells, ADH; 21NT-derived cells, DCIS; 21MT-1 cells, IMC) when grown in the mammary fat pad of nude mice, albeit after up to a year post-injection. In order to develop a more rapid, readily manipulatable in vitro assay for examining the biologic differences between these cell lines, we have made use of a 3D Matrigel system. When grown in 3D Matrigel, we have found characteristic morphologies of the three cell lines in which quantifiable aspects of the stage-specific in vivo behaviors (i.e. differences in acinar structure formation, cell polarization, cell cohesiveness, cell proliferation, cell invasion) are re-capitulated in a reproducible fashion. Gene expression profiling has revealed a characteristic pattern for each of the three cell lines. Interestingly, WNT pathway alterations are particularly predominant in the early transition from 21PTci (ADH) to 21NTci (DCIS), whereas alterations in expression of genes associated with control of cell motility and invasiveness phenomena are more prominent in the later transition of 21NTci (DCIS) to 21MT-1 (IMC). This system thus reveals potential therapeutic targets and will provide a means of testing the influences of identified genes on transitions between these stages of pre-malignant to malignant growth.
Human 21T breast epithelial cell lines mimic breast cancer progression in vivo and in vitro and show stage-specific gene expression patterns.
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View SamplesInfection with Nippostrongylus brasiliensis results in persistent changes to the lung environment. Cytokine profiling reveals a sustained increase in both Th1 and Th2 transcripts. Cellular populations of macrophages display an alternative phenotype, with upregulation of YM1, Arg1, Mrc1 as well as Class II MHC. These alternatively activated alveolar macrophages (AAAMs) also increase drastically in number. Subsequent challenge with house dust mite (HDM) Dermatophagoides pteronyssinus shows a reduced allergic phenotype, with decreased fold changes in effector cell cytokines of both the Th1 and Th2 variety indicative of the new regulatory environment established in the lung by helminth infection. Histological examination of the lung environment reveals a significant decrease in eosinophila and reduced mucous production by bronchial epithelial cells.
Hookworm-induced persistent changes to the immunological environment of the lung.
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View SamplesThe circadian clock generates biological rhythms with a period of approximately 24 hours. Using microarray experiments, we have previously shown that approximately 16% of the Arabidopsis genome is regulated in a circadian manner (Edwards et al., 2006). Previous work from our lab in modelling the molecular oscillator of Arabidopsis introduced a hypothetical component Y into an evening loop of the clock gene network (Locke et al., 2005). GIGANTEA (GI) was suggested as a strong candidate for Y based on genetic evidence and its close matching of the expression profile predicted by the mathematical modelling. Recent experimental evidence suggests that GI may only partially account for the function of Y. Thus, we are undertaking a genomics approach to identify other candidate genes that match the predicted expression profile of Y. Samples were taken from wild type and lhy cca1 double mutant seedlings from 4 timepoints around the night to day transition (-15mins, +15mins, +30mins and +60mins) after 9 days of growth in 18:6 light dark cycles. We aim to identify genes showing the light induction response predicted for Y around dawn.
The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops.
Specimen part, Time
View SamplesDupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD.
Genome-wide analysis using exon arrays demonstrates an important role for expression of extra-cellular matrix, fibrotic control and tissue remodelling genes in Dupuytren's disease.
Specimen part, Disease, Disease stage
View SamplesAnthrax lethal toxin directly targets human peripheral monocytes and causes multiple aberrant gene responses that would be expected to result in defects in human monocytes normal signaling transduction pathways and nction. This study provides further insights into the mechanisms associated with the host immune system collapse during an anthrax infection, and suggests that anthrax LT may have additional targets outside the well-known MAPK pathway.
Bacillus anthracis' lethal toxin induces broad transcriptional responses in human peripheral monocytes.
Sex, Age, Specimen part
View SamplesWe use RNA-sequencing to generate gene expression profiles of fetal mammary cells that have been induced to overexpress Sox10. These data highlight multiple important molecular mechanisms that are altered in response to this perturbation, and offer a resource to probe the basis of the stem/progenitor and EMT-like functions that are mediated by Sox10 in mammary cells. Overall design: Expression profiling of fetal mammary cells that express ectopic levels of Sox10
Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.
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View SamplesWe use RNA-sequencing to generate gene expression profiles of fetal mammary cells with unique sorting strategies. These analyses reveal that sorting fetal mammary cells with Sox10 and EpCAM sorting markers provides a stroma-free fMaSC-enriched cell population. The gene expression profiling of these cells offers a resources to probe the molecular mechanisms that specify this unique cell state. Overall design: Examination of 2 different sorting strategies for fetal mammary cells
Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.
No sample metadata fields
View SamplesThe overall aim of this experiment was to identify specific genes and molecular pathways regulated by ML290, a small molecule agonist of the relaxin receptor, RXFP1, in the context of liver fibrosis. Overall design: Whole transcriptome mRNA sequencing of transformed LX-2 cells using HiSeq platforms with paired-end 150 bp (PE 150) sequencing strategy, with four biological replicates in each treatment group.
Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis.
Specimen part, Cell line, Subject
View SamplesAlterations in the expression of key transcription factors can be harmful for pancreatic beta cell homeostasis and could lead to diabetes. This study uncovered that Prox1 overexpression obstructs beta cell maturation and results in severe hyperglycemia.
Lack of Prox1 Downregulation Disrupts the Expansion and Maturation of Postnatal Murine β-Cells.
Specimen part
View SamplesTERT is an essential protein component of telomerase, a ribonuclearprotein complex that protects chromosomal ends. Ectopic expression of TERT in mouse skin activates hair follicle stem cells and induces active growth phase of hair cycles, called anagen. This activity of TERT is independent of its reverse transcriptase function, indicating that this is a non-telomeric function of TERT.
TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.
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